Searchable Blockchain-Based Healthcare Information Exchange System to Enhance Privacy Preserving and Data Usability.

Ensuring the security and usability of electronic health records (EHRs) is important in health information exchange (HIE) systems that handle healthcare records. This study addressed the need to balance privacy preserving and data usability in blockchain-based HIE systems. We propose a searchable blockchain-based HIE system that enhances privacy preserving while improving data usability. The proposed methodology includes users collecting healthcare information (HI) from various Internet of Medical Things (IoMT) devices and compiling this information into EHR blocks for sharing on a blockchain network. This approach allows participants to search and utilize specific health data within the blockchain effectively. The results demonstrate that the proposed system mitigates the issues of traditional HIE systems by providing secure and user-friendly access to EHRs. The proposed searchable blockchain-based HIE system resolves the trade-off dilemma in HIE by achieving a balance between security and the data usability of EHRs.

Graph Learning-Based Blockchain Phishing Account Detection with a Heterogeneous Transaction Graph.

Recently, cybercrimes that exploit the anonymity of blockchain are increasing. They steal blockchain users' assets, threaten the network's reliability, and destabilize the blockchain network. Therefore, it is necessary to detect blockchain cybercriminal accounts to protect users' assets and sustain the blockchain ecosystem. Many studies have been conducted to detect cybercriminal accounts in the blockchain network. They represented blockchain transaction records as homogeneous transaction graphs that have a multi-edge. They also adopted graph learning algorithms to analyze transaction graphs. However, most graph learning algorithms are not efficient in multi-edge graphs, and homogeneous graphs ignore the heterogeneity of the blockchain network. In this paper, we propose a novel heterogeneous graph structure called an account-transaction graph, ATGraph. ATGraph represents a multi-edge as single edges by considering transactions as nodes. It allows graph learning more efficiently by eliminating multi-edges. Moreover, we compare the performance of ATGraph with homogeneous transaction graphs in various graph learning algorithms. The experimental results demonstrate that the detection performance using ATGraph as input outperforms that using homogeneous graphs as the input by up to 0.2 AUROC.

Designing arbitrary-shaped whispering-gallery cavities based on transformation optics.

A novel approach to designing anisotropic whispering gallery modes in gradient index cavities has been reported recently. These cavities, called transformation cavities, can support high-Q whispering gallery modes with directional emission. However, it is usually difficult to find the desired conformal mapping, and it may contain unwanted singularities inside. We show that arbitrary-shaped transformation cavities can be designed by virtue of a quasi-conformal mapping method without confronting such problems. Even though the quasi-conformal mapping method is exploited, we verify that the resulting mappings in our case are strictly conformal. As a demonstration, Q-factor, near field intensity, far field pattern, and phase space description of resonant modes formed in so-designed quadrupole-shaped transformation cavities are presented.

Artificial Neural Network Learns Clinical Assessment of Spasticity in Modified Ashworth Scale.

OBJECTIVE: To propose an artificial intelligence (AI)-based decision-making rule in modified Ashworth scale (MAS) that draws maximum agreement from multiple human raters and to analyze how various biomechanical parameters affect scores in MAS. DESIGN: Prospective observational study. SETTING: Two university hospitals. PARTICIPANTS: Hemiplegic adults with elbow flexor spasticity due to acquired brain injury (N=34). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Twenty-eight rehabilitation doctors and occupational therapists examined MAS of elbow flexors in 34 subjects with hemiplegia due to acquired brain injury while the MAS score and biomechanical data (ie, joint motion and resistance) were collected. Nine biomechanical parameters that quantify spastic response described by the joint motion and resistance were calculated. An AI algorithm (or artificial neural network) was trained to predict the MAS score from the parameters. Afterwards, the contribution of each parameter for determining MAS scores was analyzed. RESULTS: The trained AI agreed with the human raters for the majority (82.2%, Cohen's kappa=0.743) of data. The MAS scores chosen by the AI and human raters showed a strong correlation (correlation coefficient=0.825). Each biomechanical parameter contributed differently to the different MAS scores. Overall, angle of catch, maximum stretching speed, and maximum resistance were the most relevant parameters that affected the AI decision. CONCLUSIONS: AI can successfully learn clinical assessment of spasticity with good agreement with multiple human raters. In addition, we could analyze which factors of spastic response are considered important by the human raters in assessing spasticity by observing how AI learns the expert decision. It should be noted that few data were collected for MAS3; the results and analysis related to MAS3 therefore have limited supporting evidence.

Husimi functions at gradient index cavities designed by conformal transformation optics.

Dielectric cavity systems, which have been studied extensively so far, have uniform refractive indices of their cavities, and Husimi functions, the most widely used phase space representation of optical modes formed in the cavities, accordingly were derived only for these homogeneous index cavities. For the case of the recently proposed gradient index dielectric cavities (called as transformation cavities) designed by optical conformal mapping, we show that the phase space structure of resonant modes can be revealed through the conventional Husimi functions by constructing a reciprocal virtual space. As examples, the Husimi plots were obtained for an anisotropic whispering gallery mode (WGM) and a short-lived mode supported in a limaçon-shaped transformation cavity. The phase space description of the corresponding modes in the reciprocal virtual space is compatible with the far-field directionality of the resonant modes in the physical space.

Technical development of transcutaneous electrical nerve inhibition using medium-frequency alternating current.

BACKGROUND: Innovative technical approaches to controlling undesired sensory and motor activity, such as hyperalgesia or spasticity, may contribute to rehabilitation techniques for improving neural plasticity in patients with neurologic disorders. To date, transcutaneous electrical stimulation has used low frequency pulsed currents for sensory inhibition and muscle activation. Yet, few studies have attempted to achieve motor nerve inhibition using transcutaneous electrical stimulation. This study aimed to develop a technique for transcutaneous electrical nerve inhibition (TENI) using medium-frequency alternating current (MFAC) to suppress both sensory and motor nerve activity in humans. METHODS: Surface electrodes were affixed to the skin of eight young adults to stimulate the median nerve. Stimulation intensity was increased up to 50% and 100% of the pain threshold. To identify changes in sensory perception by transcutaneous MFAC (tMFAC) stimulation, we examined tactile and pressure pain thresholds in the index and middle fingers before and after stimulation at 10 kHz. To demonstrate the effect of tMFAC stimulation on motor inhibition, stimulation was applied while participants produced flexion forces with the index and middle fingers at target forces (50% and 90% of MVC, maximum voluntary contraction). RESULTS: tMFAC stimulation intensity significantly increased tactile and pressure pain thresholds, indicating decreased sensory perception. During the force production task, tMFAC stimulation with the maximum intensity immediately reduced finger forces by ~ 40%. Finger forces recovered immediately after stimulation cessation. The effect on motor inhibition was greater with the higher target force (90% MVC) than with the lower target (50% MVC). Also, higher tMFAC stimulation intensity provided a greater inhibition effect on both sensory and motor nerve activity. CONCLUSION: We found that tMFAC stimulation immediately inhibits sensory and motor activity. This pre-clinical study demonstrates a novel technique for TENI using MFAC stimulation and showed that it can effectively inhibit both sensory perception and motor activity. The proposed technique can be combined with existing rehabilitation devices (e.g., a robotic exoskeleton) to inhibit undesired sensorimotor activities and to accelerate recovery after neurologic injury.

Specific muscle synergies in national elite female ice hockey players in response to unexpected external perturbation.

This study aimed to investigate specific muscle synergies in elite ice hockey players indicating highly developed postural control strategies used to restore balance against unexpected external perturbations. Seven elite athletes (EA) on the women's national ice hockey team and 7 non-athletes (NA) participated in this study. Based on trajectories of centre of mass (COM), analysis periods were divided into an initial phase (a balance disturbance after perturbation onset) and a reversal phase (a balance recovery response), respectively. Muscle synergies were extracted at each phase by using non-negative matrix factorization. k-means cluster analysis was performed to arrange similar muscle synergies in all participants. EA showed significantly shorter recovery period of COM and smaller body sway than NA. In the initial phase, we identified 2 EA-specific synergies related to ankle plantar flexors or neck extensors. In the case of an NA-specific synergy, co-activation of the ankle plantar flexors and dorsiflexors was found. In the reversal phase, no specific muscle synergies were identified. As the results, EA-specific muscle synergies showed low co-activation strategy of agonists and antagonists in ankle and neck extensors. Our results could provide critical information for rehabilitation strategies in athletes requiring high postural stability.

Examining impairment of adaptive compensation for stabilizing motor repetitions in stroke survivors.

The hand, one of the most versatile but mechanically redundant parts of the human body, suffers more and longer than other body parts after stroke. One of the rehabilitation paradigms, task-oriented rehabilitation, encourages motor repeatability, the ability to produce similar motor performance over repetitions through compensatory strategies while taking advantage of the motor system's redundancy. The previous studies showed that stroke survivors inconsistently performed a given motor task with limited motor solutions. We hypothesized that stroke survivors would exhibit deficits in motor repeatability and adaptive compensation compared to healthy controls in during repetitive force-pulse (RFP) production tasks using multiple fingers. Seventeen hemiparetic stroke survivors and seven healthy controls were asked to repeatedly press force sensors as fast as possible using the four fingers of each hand. The hierarchical variability decomposition model was employed to compute motor repeatability and adaptive compensation across finger-force impulses, respectively. Stroke survivors showed decreased repeatability and adaptive compensation of force impulses between individual fingers as compared to the control (p < 0.05). The stroke survivors also showed decreased pulse frequency and greater peak-to-peak time variance than the control (p < 0.05). Force-related variables, such as mean peak force and peak force interval variability, demonstrated no significant difference between groups. Our findings indicate that stroke-induced brain injury negatively affects their ability to exploit their redundant or abundant motor system in an RFP task.

A terahertz metamaterial with unnaturally high refractive index.

Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials. The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena, among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics. Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies. Previous approaches using metamaterials were not successful in realizing broadband high refractive indices. A broadband high-refractive-index metamaterial structure was theoretically investigated only recently, but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.

Deficits in motor abilities for multi-finger force control in hemiparetic stroke survivors.

The ability to control redundant motor effectors is one of hallmarks in human motor control, and the topic has been studied extensively over several decades since the initial inquiries proposed by Nicholi Bernstein. However, our understanding of the influence of stroke on the control of redundant motor systems is very limited. This study aimed to investigate the effect of stroke-related constraints on multi-finger force control abilities in a visuomotor task. Impaired (IH) and less-impaired hands (LH) of 19 hemiparetic stroke survivors and 19 age-matched control subjects were examined. Each hand repeatedly produced isometric forces to match a target force of 5 N shown on a computer screen using all four fingers. The hierarchical variability decomposition (HVD) model was used to separate force-matching errors (motor performance) into task-relevant measures (accuracy, steadiness, and reproducibility). Task-irrelevant sources of variability in individual finger force profiles within and between trials (flexibility and multiformity) were also quantified. The IH in the stroke survivors showed deficits in motor performance attributed mainly to lower accuracy and reproducibility as compared to control hands (p < 0.05). The LH in stroke survivors showed lower reproducibility and both hands in stroke also had higher multiformity than the control hands (p < 0.05). The findings from our HVD model suggest that accuracy, reproducibility, and multiformity were mainly impaired during force-matching task in the stroke survivors. The specific motor deficits identified through the HVD model with the new conceptual framework may be considered as critical factors for scientific investigation on stroke and evidence-based rehabilitation of this population.

Ion-transfer voltammetry of perfluoroalkanesulfonates and perfluoroalkanecarboxylates: picomolar detection limit and high lipophilicity.

Here we report on ion-transfer voltammetry of perfluoroalkanesulfonates and perfluoroalkanecarboxylates at the interface between a plasticized polymer membrane and water to enable the ultrasensitive detection of these persistent environmental contaminants with adverse health effects. The ion-transfer cyclic voltammograms of the perfluoroalkyl oxoanions are obtained by using a ∼1 µm thick poly(vinyl chloride) membrane plasticized with 2-nitrophenyl octyl ether. The cyclic voltammograms are numerically analyzed to determine formal ion-transfer potentials as a measure of ion lipophilicity. The fragmental analysis of the formal potentials reveals that the 10(4) times higher lipophilicity of a perfluoroalkanesulfonate in comparison to the alkanesulfonate with the same chain length is due to the inductive effect of perfluorination on lowering the electron density of the adjacent sulfonate group, thereby weakening its hydration. The fragmental analysis also demonstrates that the lipophilicities of perfluoroalkyl and alkyl groups with the same length are nearly identical and vary with the length. Advantageously, the high lipophilicity of perfluorooctanesulfonate allows for its stripping voltammetric detection at 50 pM in the presence of 1 mM aqueous supporting electrolytes, a ∼10(7) times higher concentration. Significantly, this detection limit for perfluorooctanesulfonate is unprecedentedly low for electrochemical sensors and is lower than its minimum reporting level in drinking water set by the U.S. Environmental Protection Agency. In comparison, the voltammetric detection of perfluoroalkanecarboxylates is compromised not only by the lower lipophilicity of the carboxylate group but also by its oxidative decarboxylation at the underlying poly(3-octylthiophene)-modified gold electrode during voltammetric ion-to-electron transduction.

Development of a Targeted SN-38-Conjugate for the Treatment of Glioblastoma.

Glioblastoma (GBM) is the most aggressive and fatal brain tumor, with approximately 10,000 people diagnosed every year in the United States alone. The typical survival period for individuals with glioblastoma ranges from 12 to 18 months, with significant recurrence rates. Common therapeutic modalities for brain tumors are chemotherapy and radiotherapy. The main challenges with chemotherapy for the treatment of glioblastoma are high toxicity, poor selectivity, and limited accumulation of therapeutic anticancer agents in brain tumors as a result of the presence of the blood-brain barrier. To overcome these challenges, researchers have explored strategies involving the combination of targeting peptides possessing a specific affinity for overexpressed cell-surface receptors with conventional chemotherapy agents via the prodrug approach. This approach results in the creation of peptide drug conjugates (PDCs), which facilitate traversal across the blood-brain barrier (BBB), enable preferential accumulation of chemotherapy within the neoplastic microenvironment, and selectively target cancerous cells. This approach increases accumulation in tumors, thereby improving therapeutic efficiency and minimizing toxicity. Leveraging the affinity of the HAIYPRH (T7) peptide for the transferrin receptor (TfR) overexpressed on the blood-brain barrier and glioma cells, a novel T7-SN-38 peptide drug conjugate was developed. The T7-SN-38 peptide drug conjugate demonstrates about a 2-fold reduction in glide score (binding affinity) compared to T7 while maintaining a comparable orientation within the TfR target site using Schrödinger-2022-3 Maestro 13.3 for ligand preparation and Glide SP-Peptide docking. Additionally, SN-38 extends into a solvent-accessible region, enhancing its susceptibility to protease hydrolysis at the cathepsin B (Cat B) cleavable site. The SN-38-ether-peptide drug conjugate displayed high stability in buffer at physiological pH, and cleavage of the conjugate to release free cytotoxic SN-38 was observed in the presence of exogenous cathepsin B. The synthesized peptide drug conjugate exhibited potent cytotoxic activities in cellular models of glioblastoma in vitro. In addition, blocking transferrin receptors using the free T7 peptide resulted in a notable inhibition of cytotoxicity of the conjugate, which was reversed when exogenous cathepsin B was added to cells. This work demonstrates the potential for targeted drug delivery to the brain in the treatment of glioblastoma using the transferrin receptor-targeted T7-SN-38 conjugate.

Cutaneous sensory feedback plays a critical role in agonist-antagonist co-activation.

The purpose of this study was to investigate the role of cutaneous feedback in the agonist-antagonist co-activation mechanism during maximum voluntary force (MVF) production by the fingers. Seventeen healthy male subjects (age: 23.8 ± 1.0 years) were asked to press with maximal effort at their fingertips. Finger forces at the fingertips and muscle activities of the flexor digitorum superficialis (FDS, agonist) and extensor digitorum communis (EDC, antagonist) were recorded using force sensors and electromyography, respectively. There were two experimental conditions: with and without administration of a ring block to the fingers (i.e., anesthesia and normal conditions, or AC and NC, respectively). The ring block was used to deprive cutaneous feedback. Consistent with previous studies, finger MVF decreased significantly in AC compared with NC. Moreover, the force production of non-task fingers significantly increased in AC. Muscle activity of the EDC was significantly lower in AC than in NC; no significant changes in the FDS muscle were observed. The findings of this study show that cutaneous feedback not only increases MVF and force accuracy, but facilitates agonist-antagonist co-activation by increasing antagonist muscle activation. The results of this study imply that cutaneous feedback is linked to both primary and adjacent motor neurons.

Intensive unilateral neuromuscular training on non-dominant side of low back improves balanced muscle response and spinal stability.

Effective stabilization is important to increase sports performance. Imbalanced spinal muscle responses between the left and right sides increase the risk of spinal buckling and microtrauma at the intervertebral joints. The purpose of this study was to confirm whether intensive unilateral neuromuscular training (IUNT) focusing on the non-dominant side of the low back improves balanced muscle responses and spinal stability. The IUNT group (n = 8) performed side bridge and quadruped exercises using their non-dominant trunk muscles for 8 weeks, while the control group (n = 8) performed their regular training. Before and after the training, motion-capture cameras measured trunk angular displacement, and electromyography recorded the activities of both multifidus muscles (L4-5) during unexpected sudden forward perturbation. After the training in the IUNT group, the difference in onset time between both sides decreased to approximately 120 % compared with that before the training. The asymmetry of muscle activities also decreased from 56 to 23 %. Moreover, the angular displacement on the sagittal plane decreased to approximately 35 % after the training. We expect that IUNT focused on the non-dominant side of the low back will be useful to improve balanced back muscle responses and spinal stability during sudden trunk perturbation.

Changes in ankle range of motion and muscle strength in habitual wearers of high-heeled shoes.

BACKGROUND: Although cross-sectional biomechanical studies have reported that wearing high-heeled shoes can change the musculoskeletal system of the lower extremities, the long-term effects of wearing such shoes on the ankle remain unknown. The aim of this study was to reveal changes in ankle range of motion and muscle strength in habitual wearers of high-heeled shoes and to provide information for clinicians undertaking functional evaluations of the ankles of such patients. METHODS: Habitual wearers of high-heeled shoes (n = 10; age, 23.9 ± 2.7 years) and wearers of flat shoes (n = 10; age, 23.8 ± 2.1 years) were selectively recruited, and the range of motion, maximal voluntary isometric force, and concentric contraction power of their ankles were measured. RESULTS: Wearers of high-heeled shoes showed increased ankle range of motion on plantarflexion at 25 degrees and inversion at 10 degrees compared to flat shoe wearers (P < .05) but decreased dorsiflexion (about 17 degrees) and eversion (13 degrees; P < .05). Concentric contraction power in ankle eversion was also 2 times higher in wearers of high-heeled shoes (P < .05). CONCLUSIONS: These subjects had functional deformity of the ankle in a supinated direction and increased eversion power. CLINICAL RELEVANCE: We cautiously recommend that habitual wearers of high-heeled shoes (those who walk in such shoes for more than 5 hours more than 6 times a week) undertake intensive ankle stretching exercises in the direction of dorsiflexion as well as eversion.

Kilohertz-frequency interferential current induces hypoalgesic effects more comfortably than TENS.

Recent research on transcutaneous electrical stimulation has shown that inhibiting nerve conduction with a kilohertz frequency is both effective and safe. This study primarily aims to demonstrate the hypoalgesic effect on the tibial nerve using transcutaneous interferential-current nerve inhibition (TINI), which injects the kilohertz frequency produced by the interferential currents. Additionally, the secondary objective was to compare the analgesic effect and comfort of TINI and transcutaneous electrical nerve stimulation (TENS). Thirty-one healthy adults participated in this cross-over repeated measures study. The washout period was set to 24 h or more. Stimulus intensity was set just below the pain threshold level. TINI and TENS were applied for 20 min each. The ankle passive dorsiflexion range of motion, pressure pain threshold (PPT), and tactile threshold were measured at the baseline, pre-test, test (immediately before ceasing intervention), and post-test (30 min after ceasing intervention) sessions. After the interventions, the participants evaluated the level of discomfort for TINI and TENS on a 10 cm visual analog scale (VAS). As the results, PPT significantly increased compared to baseline in test and posttest sessions of TINI, but not in those of TENS. Also, participants reported that TENS was 36% more discomfort than TINI. The hypoalgesic effect was not significantly different between TINI and TENS. In conclusion, we found that TINI inhibited mechanical pain sensitivity and that the inhibitory effect persisted long after electrical stimulation ceased. Our study also shows that TINI provides the hypoalgesic effect more comfortably than TENS.

Combining transcutaneous interferential-current for nerve inhibition with a robotic assistant device for increasing ankle dorsiflexion in walking.

BACKGROUND: A kilohertz-frequency alternating current transcutaneously applied was introduced as a novel neuromodulation technology for nerve inhibition innervating antagonist muscles. Combining this electrical nerve inhibition with a robotic assistance device has been proposed but not investigated. RESEARCH QUESTION: This study aimed to demonstrate the effect of combining electrical nerve inhibition with a wearable robotic device on increasing ankle dorsiflexion during walking. We hypothesized that the wearable robotic device would elicit a greater ankle dorsiflexion angle with the same force in walking by applying the transcutaneous interferential-current nerve inhibition (TINI) technique to the tibial nerve. METHODS: Eleven healthy young adults performed three experimental conditions. The ankle assistance (AA) condition was walking while wearing an ankle device with operating dorsiflexion assistance during pre-swing and swing phases. For the ankle assistance with electrical stimulation (AE) condition, TINI on the tibial nerve was additionally applied from the AA condition. In the ankle non-assistance (AN) condition, participants wore the device, but assistance was not provided. The joint angles during walking were measured and digitized through a motion analysis system. RESULTS: During a gait cycle, immediate changes in ankle joint motions were observed in the sagittal plane. In the pre-swing phase, ankle dorsiflexion angle was significantly greater in AE condition than AA and AN. There was no significant difference in joint angle between AA and AN. SIGNIFICANCE: This study demonstrates the effectiveness of combining TINI with a wearable robotic ankle device in increasing dorsiflexion angle during the pre-swing phase. This finding provides the feasibility of using TINI as a neuromodulation technique for assisting functional movement in human walking.

Evaluation of the resection efficiency and safety of an enhanced power plasma generator using cadaveric intervertebral discs.

Plasma energy has been used to provide minimally invasive interventional treatment for spinal problems. However, this procedure has been used for limited indications mainly because of its small resection range. To overcome this problem, we designed the enhanced power plasma device. This device seeks to maximize the resection area by modifying the electrode arrangement and enhancing the maximum electric power. The purpose of this study is to assess the efficiency and safety of this newly designed plasma generator, a device for percutaneous disc decompression. We performed an intradiscal procedure on 7 fresh human cadaver lumbar spine specimens using the enhanced power plasma under C-arm fluoroscopic guidance at various voltages. As a result, the volume of the removed area was proportional to the applied magnitude of the electric power level. In particular, under the high-power level condition after 500 s treatment, nearly the entire nucleus pulposus was eliminated. The generated plasma density also tends to grow along with the given electric power. The highest level of temperature rise did not exceed the level that would lead to degeneration in the collagen tissue of the intervertebral disc. Histopathologic examination also demonstrated that there was no thermal damage to the surrounding neural tissues. In conclusion, we speculate that the concepts of this newly designed enhanced plasma generator could be applied to remove huge disc materials without thermal or structural damage to the adjacent target tissues in future spine clinics.

Streptococcus mutans GS-5 antigen I/II stimulates cell survival in serum deprived-cultures through PI3K/Akt pathways.

The antigen I/II (AgI/II) protein is a major surface protein that mediates the attachment of Streptococcus mutans (S. mutans) to the saliva-coated pellicle. Numerous studies have investigated not only the mechanisms by which AgI/II signaling is transduced within cells, but have also attempted to use AgI/II-specific antibodies to treat dental caries and host immune responses. However, little information is available about the effects of AgI/II on basic cellular events in bone cells. In this study, we examined the effects of the His-tagged recombinant N-terminal half of the AgI/II protein (rAgI/II-N) generated from S. mutans GS-5 on the viability, proliferation, and cell cycle progression of primary calvarial osteoblasts. We also investigated the mechanisms involved in the rAgI/II-N-mediated survival of serum-starved osteoblasts. We found that rAgI/II treatment attenuated the serum deprivation-induced decrease in cell viability and proliferation of osteoblasts. rAgI/II-N also prevented the loss of mitochondrial membrane potential (MMP), alterations in levels of two key mitochondrial Bcl-2 family proteins, and the accumulation of numerous cells into the sub-G(1) phase that were observed in serum-starved osteoblasts. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), but not of extracellular signal-regulated kinase or Ras, blocked the rAgI/II-N-mediated protection against serum deprivation-induced cell death. Additional experiments revealed that the integrin α5ß1-mediated PI3K pathway is required for rAgI/II-N-mediated Akt phosphorylation in osteoblasts. Collectively, these results suggest that rAgI/II-N induces survival signals in serum-starved osteoblasts through integrin-induced PI3K/Akt signaling pathways.

External walking environment differentially affects muscle synergies in children with cerebral palsy and typical development.

Despite external environmental changes in walking, such as manipulating gait speed, previous studies have shown that the underlying muscle synergy structures (synergy weights or vectors) rarely vary. The purpose of this study is to examine if external environmental changes to the walking task influence muscle synergies in children with cerebral palsy (CP) and/or typical development (TD). To identify muscle synergies, we extracted muscle synergies from eight children with CP and eight age-matched TD in three treadmill walking conditions, e.g., baseline (adjusted to individual comfortable walking speed), variable speed (VS), or restricted foot width (RW). Then, we grouped similar muscle synergies using k-mean clustering and discriminant analyses from all datasets of individual synergy structures. Proportion tests exhibited six clusters of muscle synergies predominantly arising from children with CP and four clusters from children with TD. Also, the proportion of muscle synergies was significantly different in four of the CP-preferred clusters across conditions. Specifically, the proportion of the baseline condition was significantly different from VS and RW conditions in one and two clusters, respectively. The proportion was significantly different between VS and RW conditions in four clusters. Cadence and step lengths differed across conditions but not groups which makes the group differences in proportion even more notable. In contrast, step width, while significantly lower in CP, did not differ across conditions. Our findings demonstrate that muscle synergies in children with CP are more sensitive to changes in the external walking environment than in typically developing children.