The type 3 secretion system requires actin polymerization to open translocon pores.

Many bacterial pathogens require a type 3 secretion system (T3SS) to establish a niche. Host contact activates bacterial T3SS assembly of a translocon pore in the host plasma membrane. Following pore formation, the T3SS docks onto the translocon pore. Docking establishes a continuous passage that enables the translocation of virulence proteins, effectors, into the host cytosol. Here we investigate the contribution of actin polymerization to T3SS-mediated translocation. Using the T3SS model organism Shigella flexneri, we show that actin polymerization is required for assembling the translocon pore in an open conformation, thereby enabling effector translocation. Opening of the pore channel is associated with a conformational change to the pore, which is dependent upon actin polymerization and a coiled-coil domain in the pore protein IpaC. Analysis of an IpaC mutant that is defective in ruffle formation shows that actin polymerization-dependent pore opening is distinct from the previously described actin polymerization-dependent ruffles that are required for bacterial internalization. Moreover, actin polymerization is not required for other pore functions, including docking or pore protein insertion into the plasma membrane. Thus, activation of the T3SS is a multilayered process in which host signals are sensed by the translocon pore leading to the activation of effector translocation.

Validating stroke-induced bilateral ankle coordination deficits using bilateral ankle measure relationship with motor functions in lower limbs.

BACKGROUND: Coordinated control between the bilateral ankle joints plays an important role in performing daily life functions, such as walking and running. However, few studies have explored the impact of stroke on movement disorders that decrease the coordination control of the bilateral extremities and may decrease daily activities that require coordination control of the bilateral ankles. This study aimed to investigate the coordination control of the bilateral ankles using a novel bilateral ankle measurement system and evaluate the relationship of bilateral movement coordination control deficits with motor and functional performances of the lower extremities in patients with stroke. METHODS: Twenty-one healthy adults (36.5 ± 13.2 y/o) and 19 patients with chronic stroke (58.7 ± 10.5 y/o) were enrolled. A novel measurement device with embedded rotary potentiometers was used to evaluate bilateral ankle coordination control. Participants were asked to move their dominant (non-paretic) foot from dorsiflexion to plantarflexion position and non-dominant (paretic) foot from dorsiflexion to plantarflexion position (condition 1) simultaneously, and vice versa (condition 2). Alternating time and angle for coordination control with movements of both ankles were calculated for each condition. Motor and functional performance measurements of the lower extremities included the lower-extremity portion of the Fugl-Meyer assessment (FMA-LE), Berg Balance Test (BBS), Timed Up and Go Test (TUG), and Barthel Index (BI). RESULTS: Compared with the healthy group, alternating time was shorter in the stroke group by 8.3% (p = 0.015), and the alternating angles of conditions 1 and 2 were significantly higher than those of the healthy group by 1.4° (p = 0.001) and 2.5° (p = 0.013), respectively. The alternating angle in condition 2 showed moderate correlations with TUG (r = 0.512; p = 0.025), 10-m walk (r = 0.747; p < 0.001), gait speed (r = - 0.497 to - 0.491; p < 0.05), length (r = - 0.518 to - 0.551; p < 0.05), and BI (r = - 0.457; p = 0.049). CONCLUSION: Stroke decreases alternating time, increases alternating angle, and shows bilateral ankle coordination control deficits temporally and spatially. A higher alternating angle is moderately to highly associated with motor function and lower limb function in patients with stroke.

The impact of aging and reaching movements on grip stability control during manual precision tasks.

BACKGROUND: Operating an object by generating stable hand-grip force during static or dynamic posture control of the upper extremities simultaneously is an important daily activity. Older adults require different attentional resources during grip strength control and arm movements. However, the impact of aging and reaching movements on precise grip strength and stability control among older adults is not well understood. This study investigated the impact of aging and reaching movements on grip strength and stability control in both hands of the upper extremities. METHODS: Fifty healthy young adults (age: 28.8 ± 14.0 years) and 54 healthy older adults (73.6 ± 6.3 years) were recruited to perform isometric grip strength test at 20% maximal voluntary contraction as the target force during three manual precision tasks simultaneously: stationary task (without arm movements), forward-reach task, and backward-reach task. The average grip force (in kg) and coefficient of variation values (expressed as a percentage) during manual precision tasks were calculated to determine the quality of participants' grip strength. The deviation error, absolute error, and force-stability index values were calculated to determine the strength control relative to the target force. RESULTS: For both the young and older groups, the force-stability index values in both hands were significantly higher during forward- and backward-reaching movements than in the stationary condition (p < 0.05). The older group exhibited a significantly lower hand-grip strength and stability of strength control in both hands than the young group (p < 0.05). CONCLUSIONS: Aging and reaching task performance reduced the grip strength of participants and increased the variations in strength control of both hands relative to the target force, indicating that older adults exhibit poor grip strength and stability control when performing arm-reaching movements. These findings may help clinical therapists in establishing objective indexes for poor grip-stability control screening and developing appropriate rehabilitation programs or health-promotion exercises that can improve grip strength and stability control in older people.

Impacts of tai chi exercise on functional fitness in community-dwelling older adults with mild degenerative knee osteoarthritis: a randomized controlled clinical trial.

BACKGROUND: Degenerative osteoarthritis (OA) often leads to pain and stiffness of the affected joints, which may affect the physical performance and decrease the quality of life of people with degenerative knee OA. Compared to traditional exercise, tai chi is a safe exercise with slow movements which can facilitate physical functioning and psychological well being, and might be suitable for improving the physical activities of older adults with knee OA. Therefore, this study investigated the impacts of tai chi exercise on the functional fitness of community-dwelling older adults with degenerative knee OA. METHODS: Sixty-eight community-dwelling older adults with knee OA were recruited from the local community to participate in this randomized controlled clinical trial. All subjects were randomly assigned to either an TCE group that practiced tai chi exercise (TCE) (n = 36) or a control group (CON) (n = 32) that received regular health education programs twice per week for 12 weeks. Outcome measurements were determined using functional fitness tests before and after the intervention, including a 30-s chair stand (number of repeats), 30-s arm-curl (number of repeats), 2-min step (number of steps), chair sit-and-reach (reaching distance, cm), back-scratch flexibility (distance between hands, cm), single-leg stand (time, s), functional reach (reaching distance, cm), 8-foot up-and-go (time, s), and 10-m walk tests (time, s). Pre-post comparisons of functional fitness were analyzed using the ANCOVA test with SPSS software version 18.0. RESULTS: Results revealed that participants' functional fitness in the TCE group had significantly higher adjusted mean post-tests scores than that in the CON group after the intervention, including the 8-foot up-and-go (s) (mean difference [MD]=-2.92 [-3.93, -1.91], p = 2.39*10- 7), 30-s arm curl (MD = 4.75 (2.76, 6.73), p = 1.11*10- 5), 2-min step (MD = 36.94 [23.53, 50.36], p = 7.08*10- 7), 30-s chair stand (MD = 4.66 [2.97, 6.36], p = 6.96*10- 7), functional-reach (MD = 5.86 [3.52, 8.20], p = 4.72*10- 6), single-leg stand with eyes closed (MD = 3.44 [1.92, 4.97], p = 2.74*10- 5), chair sit-and-reach (MD = 3.93 [1.72, 6.15], p = 0.001), and single-leg stand with eyes opened (MD = 17.07 [6.29, 27.85], p = 0.002), with large effect sizes (η²=0.14 ~ 0.34). CONCLUSIONS: Community-dwelling older adults with knee OA in the TCE group had better functional fitness performances after the 12-week tai chi intervention than those receiving only health education.

User Local Coordinate-Based Accompanying Robot for Human Natural Movement of Daily Life.

Considering the trend of aging societies, accompanying technology can help frail, elderly individuals participate in daily activities. The ideal accompanying robot should accompany the user in a proper position according to the activity scenarios and context; the prerequisite is that the accompanying robot should quickly move to a designated position and closely maintain it regardless of the direction in which the user moves. This paper proposes a user local coordinate-based strategy to satisfy this need. As a proof of concept, a novel "string-pot" approach was utilized to measure the position difference between the robot and the target. We implemented the control strategy and assessed its performance in our gait lab. The results showed that the robot can follow the user in the designated position while the user performs forward, backward, and lateral movements, turning, and walking along a curve.

Online Gait Detection with an Automatic Mobile Trainer Inspired by Neuro-Developmental Treatment.

This paper demonstrates the development of an automatic mobile trainer employing inertial movement units (IMUs). The device is inspired by Neuro-Developmental Treatment (NDT), which is an effective rehabilitation method for stroke patients that promotes the relearning of motor skills by repeated training. However, traditional NDT training is very labor intensive and time consuming for therapists, thus, stroke patients usually cannot receive sufficient rehabilitation training. Therefore, we developed a mobile assisted device that can automatically repeat the therapists' intervention and help increase patient training time. The proposed mobile trainer, which allows the users to move at their preferred speeds, consists of three systems: the gait detection system, the motor control system, and the movable mechanism. The gait detection system applies IMUs to detect the user's gait events and triggers the motor control system accordingly. The motor control system receives the triggering signals and imitates the therapist's intervention patterns by robust control. The movable mechanism integrates these first two systems to form a mobile gait-training device. Finally, we conducted preliminary tests and defined two performance indexes to evaluate the effectiveness of the proposed trainer. Based on the results, the mobile trainer is deemed successful at improving the testing subjects' walking ability.

Comparative Genomics Reveals the Diversity of Restriction-Modification Systems and DNA Methylation Sites in Listeria monocytogenes.

Listeria monocytogenes is a bacterial pathogen that is found in a wide variety of anthropogenic and natural environments. Genome sequencing technologies are rapidly becoming a powerful tool in facilitating our understanding of how genotype, classification phenotypes, and virulence phenotypes interact to predict the health risks of individual bacterial isolates. Currently, 57 closed L. monocytogenes genomes are publicly available, representing three of the four phylogenetic lineages, and they suggest that L. monocytogenes has high genomic synteny. This study contributes an additional 15 closed L. monocytogenes genomes that were used to determine the associations between the genome and methylome with host invasion magnitude. In contrast to previous findings, large chromosomal inversions and rearrangements were detected in five isolates at the chromosome terminus and within rRNA genes, including a previously undescribed inversion within rRNA-encoding regions. Each isolate's epigenome contained highly diverse methyltransferase recognition sites, even within the same serotype and methylation pattern. Eleven strains contained a single chromosomally encoded methyltransferase, one strain contained two methylation systems (one system on a plasmid), and three strains exhibited no methylation, despite the occurrence of methyltransferase genes. In three isolates a new, unknown DNA modification was observed in addition to diverse methylation patterns, accompanied by a novel methylation system. Neither chromosome rearrangement nor strain-specific patterns of epigenome modification observed within virulence genes were correlated with serotype designation, clonal complex, or in vitro infectivity. These data suggest that genome diversity is larger than previously considered in L. monocytogenes and that as more genomes are sequenced, additional structure and methylation novelty will be observed in this organism. IMPORTANCE: Listeria monocytogenes is the causative agent of listeriosis, a disease which manifests as gastroenteritis, meningoencephalitis, and abortion. Among Salmonella, Escherichia coli, Campylobacter, and Listeria-causing the most prevalent foodborne illnesses-infection by L. monocytogenes carries the highest mortality rate. The ability of L. monocytogenes to regulate its response to various harsh environments enables its persistence and transmission. Small-scale comparisons of L. monocytogenes focusing solely on genome contents reveal a highly syntenic genome yet fail to address the observed diversity in phenotypic regulation. This study provides a large-scale comparison of 302 L. monocytogenes isolates, revealing the importance of the epigenome and restriction-modification systems as major determinants of L. monocytogenes phylogenetic grouping and subsequent phenotypic expression. Further examination of virulence genes of select outbreak strains reveals an unprecedented diversity in methylation statuses despite high degrees of genome conservation.

Development of a modularized seating system to actively manage interface pressure.

Pressure ulcers can be a fatal complication. Many immobile wheelchair users face this threat. Current passive and active cushions do reduce the incidence of pressure ulcers and they have different merits. We proposed an active approach to combine their advantages which is based on the concept that the interface pressure can be changed with different supporting shapes. The purpose of this paper is to verify the proposed approach. With practical applications in mind, we have developed a modular system whose support surface is composed by height-adjustable support elements. Each four-element module was self-contained and composed of force sensors, position sensors, linear actuators, signal conditioners, driving circuits, and signal processors. The modules could be chained and assembled together easily to form different-sized support surfaces. Each support element took up a 3 cm × 3 cm supporting area. The displacement resolution was less than 0.1 mm and the force sensor error was less than 1% in the 2000 g range. Each support element of the system could provide 49 N pushing force (408 mmHg over the 3 cm × 3 cm area) at a speed of 2.36 mm/s. Several verification tests were performed to assess the whole system's feasibility. Further improvements and clinical applications were discussed. In conclusion, this modularized system is capable of actively managing interface pressure in real time.

A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria.

Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system-a contact-dependent DNA delivery nanomachine-we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as directing the antibacterial activity of programmed inhibitor cells toward target bacteria in mixed populations.

Recent insights into type-3 secretion system injectisome structure and mechanism of human enteric pathogens.

Type-3 secretion system injectisomes are multiprotein complexes that translocate bacterial effector proteins from the cytoplasm of gram-negative bacteria directly into the cytosol of eukaryotic host cells. These systems are present in more than 30 bacterial species, including numerous human, animal, and plant pathogens. We review recent discoveries of structural and molecular mechanisms of effector protein translocation through the injectisomes and recent advances in the understanding of mechanisms of activation of effector protein secretion.

Interactive wiimote gaze stabilization exercise training system for patients with vestibular hypofunction.

BACKGROUND: Peripheral vestibular hypofunction is a major cause of dizziness. When complicated with postural imbalance, this condition can lead to an increased incidence of falls. In traditional clinical practice, gaze stabilization exercise is commonly used to rehabilitate patients. In this study, we established a computer-aided vestibular rehabilitation system by coupling infrared LEDs to an infrared receiver. This system enabled the subjects' head-turning actions to be quantified, and the training was performed using vestibular exercise combined with computer games and interactive video games that simulate daily life activities. METHODS: Three unilateral and one bilateral vestibular hypofunction patients volunteered to participate in this study. The participants received 30 minutes of computer-aided vestibular rehabilitation training 2 days per week for 6 weeks. Pre-training and post-training assessments were completed, and a follow-up assessment was completed 1 month after the end of the training period. RESULTS: After 6 weeks of training, significant improvements in balance and dynamic visual acuity (DVA) were observed in the four participants. Self-reports of dizziness, anxiety and depressed mood all decreased significantly. Significant improvements in self-confidence and physical performance were also observed. The effectiveness of this training was maintained for at least 1 month after the end of the training period. CONCLUSION: Real-time monitoring of training performance can be achieved using this rehabilitation platform. Patients demonstrated a reduction in dizziness symptoms after 6 weeks of training with this short-term interactive game approach. This treatment paradigm also improved the patients' balance function. This system could provide a convenient, safe and affordable treatment option for clinical practitioners.

Clinical applications and consideration of interventions of electrotherapy for orthopedic and neurological rehabilitation.

Electrotherapy or electrical stimulation (ES) is a part of clinical intervention in the rehabilitation field. With rehabilitation intervention, electrotherapy may be provided as a treatment for pain relief, strengthening, muscle education, wound recovery, or functional training. Although these interventions may not be considered as the primary therapy for patients, the advantages of the ease of operation, lower costs, and lower risks render ES to be applied frequently in clinics. There have also been emerging ES tools for brain modulation in the past decade. ES interventions are not only considered analgesics but also as an important assistive therapy for motor improvement in orthopedic and neurological rehabilitation. In addition, during the coronavirus disease pandemic, lockdowns and self-quarantine policies have led to the discontinuation of orthopedic and neurological rehabilitation interventions. Therefore, the feasibility and effectiveness of home-based electrotherapy may provide opportunities for the prevention of deterioration or extension of the original therapy. The most common at-home applications in previous studies showed positive effects on pain relief, functional ES, muscle establishment, and motor training. Currently, there is a lack of certain products for at-home brain modulation; however, transcranial direct current stimulation has shown the potential of future home-based rehabilitation due to its relatively small and simple design. We have organized the features and applications of ES tools and expect the future potential of remote therapy during the viral pandemic.

Deep learning to infer visual acuity from optical coherence tomography in diabetic macular edema.

Purpose: Diabetic macular edema (DME) is one of the leading causes of visual impairment in diabetic retinopathy (DR). Physicians rely on optical coherence tomography (OCT) and baseline visual acuity (VA) to tailor therapeutic regimen. However, best-corrected visual acuity (BCVA) from chart-based examinations may not wholly reflect DME status. Chart-based examinations are subjected findings dependent on the patient's recognition functions and are often confounded by concurrent corneal, lens, retinal, optic nerve, or extraocular disorders. The ability to infer VA from objective optical coherence tomography (OCT) images provides the predicted VA from objective macular structures directly and a better understanding of diabetic macular health. Deviations from chart-based and artificial intelligence (AI) image-based VA will prompt physicians to assess other ocular abnormalities affecting the patients VA and whether pursuing anti-VEGF treatment will likely yield increment in VA. Materials and methods: We enrolled a retrospective cohort of 251 DME patients from Big Data Center (BDC) of Taipei Veteran General Hospital (TVGH) from February 2011 and August 2019. A total of 3,920 OCT images, labeled as "visually impaired" or "adequate" according to baseline VA, were grouped into training (2,826), validation (779), and testing cohort (315). We applied confusion matrix and receiver operating characteristic (ROC) curve to evaluate the performance. Results: We developed an OCT-based convolutional neuronal network (CNN) model that could classify two VA classes by the threshold of 0.50 (decimal notation) with an accuracy of 75.9%, a sensitivity of 78.9%, and an area under the ROC curve of 80.1% on the testing cohort. Conclusion: This study demonstrated the feasibility of inferring VA from routine objective retinal images. Translational relevance: Serves as a pilot study to encourage further use of deep learning in deriving functional outcomes and secondary surrogate endpoints for retinal diseases.

Hematology and Culture Assessment of Cranially Implanted Rhesus Macaques (Macaca mulatta).

The use of percutaneous cranial implants in rhesus macaques (Macaca mulatta) has long been a valuable tool for neuroscience research. However, when treating and assessing these animals, veterinarians are required to make assumptions about diagnostic results due to a lack of research into how these implants affect physiology. Microbial cultures of cranial implant sites show an abundance of colonizing bacteria, but whether these microbes affect animal health and wellbeing is poorly understood. In addition, microbial antibiotic resistance can present significant health concerns for both the animals and the researchers. To help elucidate the relationship between percutaneous cranial implants and blood parameters, complete blood cell counts and serum chemistry results were assessed on 57 nonhuman primates at our institution from September 2001 to March 2017. Generalized estimating equations were used to compare the results before and after an animal's first implant surgery. This modelling showed that cranial implants were a significant predictor of alterations in the number of neutrophils, lymphocytes, and red blood cells, and in the concentration of hemoglobin, alkaline phosphatase, creatinine, calcium, phos- phorus, total protein, albumin, and globulin. Anaerobic and aerobic bacterial cultures were performed to identify bacteria associated with cranial implants. Staphylococcus spp., Streptococcus spp., and Corynebacterium spp. comprised the majority of the aerobic bacterial isolates, while Fusobacterium spp., Peptostreptococcus spp. and Bacterioides fragilis comprised the majority of anaerobic bacterial isolates. Using a Pearson r correlation for statistical analysis, we assessed whether any of these bacterial isolates developed antibiotic resistances over time. Cefazolin, the most frequently used antibiotic in monkeys in this study, was the only antimicrobial out of 41 agents tested to which bacteria developed resistance over time. These results indicate that percutaneous implants are associated with a generalized inflammatory state, multiple bacterial species are present at the implant site, and these bacteria may contribute to the inflammatory response.

Topology and Contribution to the Pore Channel Lining of Plasma Membrane-Embedded Shigella flexneri Type 3 Secretion Translocase IpaB.

Shigella spp. are human bacterial pathogens that cause bacillary dysentery. Virulence depends on a type 3 secretion system (T3SS), a highly conserved structure present in multiple important human and plant pathogens. Upon host cell contact, the T3SS translocon is delivered to the host membrane, facilitates bacterial docking to the membrane, and enables delivery of effector proteins into the host cytosol. The Shigella translocon is composed of two proteins, IpaB and IpaC, which together form this multimeric structure within host plasma membranes. Upon interaction of IpaC with host intermediate filaments, the translocon undergoes a conformational change that allows for bacterial docking onto the translocon and, together with host actin polymerization, enables subsequent effector translocation through the translocon pore. To generate additional insights into the translocon, we mapped the topology of IpaB in plasma membrane-embedded pores using cysteine substitution mutagenesis coupled with site-directed labeling and proximity-enabled cross-linking by membrane-permeant sulfhydryl reactants. We demonstrate that IpaB function is dependent on posttranslational modification by a plasmid-encoded acyl carrier protein. We show that the first transmembrane domain of IpaB lines the interior of the translocon pore channel such that the IpaB portion of the channel forms a funnel-like shape leading into the host cytosol. In addition, we identify regions of IpaB within its cytosolic domain that protrude into and are closely associated with the pore channel. Taken together, these results provide a framework for how IpaB is arranged within translocons natively delivered by Shigella during infection. IMPORTANCE Type 3 secretion systems are nanomachines employed by many bacteria, including Shigella, which deliver into human cells bacterial virulence proteins that alter cellular function in ways that promote infection. Delivery of Shigella virulence proteins occurs through a pore formed in human cell membranes by the IpaB and IpaC proteins. Here, we define how IpaB contributes to the formation of pores natively delivered into human cell membranes by Shigella flexneri. We show that a specific domain of IpaB (transmembrane domain 1) lines much of the pore channel and that portions of IpaB that lie in the inside of the human cell loop back into and/or are closely associated with the pore channel. These findings provide new insights into the organization and function of the pore in serving as the conduit for delivery of virulence proteins into human cells during Shigella infection.

Gaze shift dynamic visual acuity: A functional test of gaze stability that distinguishes unilateral vestibular hypofunction.

BACKGROUND: Embedded within most rapid head rotations are gaze shifts, which is an initial eye rotation to a target of interest, followed by a head rotation towards the same target. Gaze shifts are used to acquire an image that initially is outside of the participant's current field of vision. Currently, there are no tools available that evaluate the functional relevance of a gaze shift. OBJECTIVE: The purpose of our study was to measure dynamic visual acuity (DVA) while performing a gaze shift. METHODS: Seventy-one healthy participants (42.79±16.89 years) and 34 participants with unilateral vestibular hypofunction (UVH) (54.59±20.14 years) were tested while wearing an inertial measurement unit (IMU) sensor on the head and walking on a treadmill surrounded by three monitors. We measured visual acuity during three subcomponent tests: standing (static visual acuity), while performing an active head rotation gaze shift, and an active head rotation gaze shift while walking (gsDVAw). RESULTS: While doing gsDVAw, patients with Left UVH (n = 21) had scores worse (p = 0.023) for leftward (0.0446±0.0943 LogMAR) head rotation compared with the healthy controls (-0.0075±0.0410 LogMAR). Similarly, patients with right UVH (N = 13) had worse (p = 0.025) gsDVAw for rightward head motion (0.0307±0.0481 LogMAR) compared with healthy controls (-0.0047±0.0433 LogMAR). As a whole, gsDVAw scores were worse in UVH compared to the healthy controls when we included the ipsilesional head rotation on both sides gsDVAw (0.0061±0.0421 LogMAR healthy vs. 0.03926±0.0822 LogMAR UVH, p = 0.003). Controlling for age had no effect, the gsDVAw scores of the patients were always worse (p < 0.01). CONCLUSION: The gaze shift DVA test can distinguish gaze stability in patients with UVH from healthy controls. This test may be a useful measure of compensation for patients undergoing various therapies for their vestibular hypofunction.

Frontier review of the roles of exosomes in osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease; however, its exact pathophysiology and early diagnosis are still a challenge. Growing attention to the exosomes may inspire innovations that would make the current management of OA more effective. The exosomes in synovial fluid are relatively stable, and they can be easily isolated by the relatively noninvasive procedure of liquid biopsy to provide diagnostic and monitoring value. Some miRNAs (miR-504, miR-146a, miR-26a, miR-200c, and miR-210) have been known to be secreted in exosomes of OA patients. On the other hand, intraarticular injection of platelet-rich plasma (PRP) is becoming a popular therapy for OA patients. PRP is also a source of exosomes and their numerous contents. It is evident from the literature that PRP-derived exosomes can induce chondrogenic gene expression in OA chondrocytes. Here, we review the latest findings on the roles of exosomes in OA with the emphasis on PRP-derived exosomes and their potential applications for treating OA.

Effect of noisy galvanic vestibular stimulation on dynamic posture sway under visual deprivation in patients with bilateral vestibular hypofunction.

A single-blind study to investigate the effects of noisy galvanic vestibular stimulation (nGVS) in straight walking and 2 Hz head yaw walking for healthy and bilateral vestibular hypofunction (BVH) participants in light and dark conditions. The optimal stimulation intensity for each participant was determined by calculating standing stability on a force plate while randomly applying six graded nGVS intensities (0-1000 µA). The chest-pelvic (C/P) ratio and lateral deviation of the center of mass (COM) were measured by motion capture during straight and 2 Hz head yaw walking in light and dark conditions. Participants were blinded to nGVS served randomly and imperceivably. Ten BVH patients and 16 healthy participants completed all trials. In the light condition, the COM lateral deviation significantly decreased only in straight walking (p = 0.037) with nGVS for the BVH. In the dark condition, both healthy (p = 0.026) and BVH (p = 0.017) exhibited decreased lateral deviation during nGVS. The C/P ratio decreased significantly in BVH for 2 Hz head yaw walking with nGVS (p = 0.005) in light conditions. This study demonstrated that nGVS effectively reduced walking deviations, especially in visual deprived condition for the BVH. Applying nGVS with different head rotation frequencies and light exposure levels may accelerate the rehabilitation process for patients with BVH.Clinical Trial Registration This clinical trial was prospectively registered at www.clinicaltrials.gov with the Unique identifier: NCT03554941. Date of registration: (13/06/2018).

Smartphone frailty screening: Development of a quantitative early detection method for the frailty syndrome.

BACKGROUND: Frailty syndrome in older population generates formidable social cost. The early detection of "prefrail" stage is essential so that interventions could be performed to prevent deterioration. The purpose of this study was to organize appropriate physical performance tests into a computerized early frailty screening platform, called frailty assessment tools (FAT) system, to detect individuals who are in the prefrail stage. METHODS: Four switches, one distance meter, and one power measure were adopted to build the FAT system that could perform six physical performance tests including single leg standing (SLS), repeated chair rise, timed up and go, self-selected walking speed, functional reach, and grip power. Participants over 65 years old were recruited and classified into three groups according to Fried criteria. The differences in variables between prefrail and robust groups were compared by the χ test, independent samples t test, and Mann-Whitney U test, for nominal variables, normal, and non-normal distributive continuous variables, respectively. The statistically significant level was set at 0.05 (α = 0.05). RESULTS: Only SLS did not reach significance to distinguish prefrail from robust. Among 35 participants (73.23 ± 5.70 years old), the FAT score predicted that 90.73 ± 19.95% of pre-frail subjects and 15.01 ± 25.25% of robust subjects were in the prefrail stage. CONCLUSION: The FAT system, which provides results immediately, is an advantageous alternative to traditional manual measurements. The use of the FAT score for predicting the prefrail stage will help to provide early intervention to prevent individuals from progressing into frailty. The FAT system provides a more convenient and comprehensive frailty screening. Using this computerized automatic screening platform, it may be possible to expand the scope of frailty prevention.

Development of a Computerized Device for Evaluating Vestibular Function in Locomotion: A New Evaluation Tool of Vestibular Hypofunction.

To evaluate vestibular function in the clinic, current assessments are applied under static conditions, such as with the subject in a sitting or supine position. Considering the complexities of daily activities, the combination of dynamic activities, dynamic visual acuity (DVA) and postural control could produce an evaluation that better reflects vestibular function in daily activities. Objective: To develop a novel sensor-based system to investigate DVA, walking trajectory, head and trunk movements and the chest-pelvis rotation ratio during forward and backward overground walking in both healthy individuals and patients with vestibular hypofunction. Methods: Fifteen healthy subjects and 7 patients with bilateral vestibular hypofunction (BVH) were recruited for this study. Inertial measurement units were placed on each subject's head and torso. Each subject walked forward and backward for 5 m twice with 2 Hz head yaw. Our experiment comprised 2 stages. In stage 1, we measured forward (FW), backward (BW), and medial-lateral (MLW) walking trajectories; head and trunk movements; and the chest-pelvis rotation ratio. In stage 2, we measured standing and locomotion DVA (loDVA). Using Mann-Whitney U-test, we compared the abovementioned parameters between the 2 groups. Results: Patients exhibited an in-phase chest/pelvis reciprocal rotation ratio only in FW. The walking trajectory deviation, calculated by normalizing the summation of medial-lateral swaying with 1/2 body height (%), was significantly larger (FW mean ± standard deviation: 20.4 ± 7.1% (median (M)/interquartile range (IQR): 19.3/14.4-25.2)in healthy vs. 43.9 ± 27. 3% (M/IQR: 36.9/21.3-56.9) in patients, p = 0.020)/(BW mean ± standard deviation: 19.2 ± 11.5% (M/IQR: 13.6/10.4-25.3) in healthy vs. 29.3 ± 6.4% (M/IQR: 27.7/26.5-34.4) in patients, p = 0.026), and the walking DVA was also significantly higher (LogMAR score in the patient group [FW LogMAR: rightDVA: mean ± standard deviation:0.127 ± 0.081 (M/IQR: 0.127/0.036-0.159) in healthy vs. 0.243 ± 0.101 (M/IQR: 0.247/0.143-0.337) in patients (p = 0.013) and leftDVA: 0.136 ± 0.096 (M/IQR: 0.127/0.036-0.176) in healthy vs. 0.258 ± 0.092 (M/IQR: 0.247/0.176-0.301) in patients (p = 0.016); BW LogMAR: rightDVA: mean ± standard deviation: 0.162 ± 0.097 (M/IQR: 0.159/0.097-0.273) in healthy vs. 0.281 ± 0.130 (M/IQR: 0.273/0.176-0.418) in patients(p = 0.047) and leftDVA: 0.156 ± 0.101 (M/IQR: 0.159/0.097-0.198) in healthy vs. 0.298 ± 0.153 (M/IQR: 0.2730/0.159-0.484) in patients (p = 0.038)]. Conclusions: Our sensor-based vestibular evaluation system provided a more functionally relevant assessment for the identification of BVH patients.