miR-4284 Functions as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting Glutamate Decarboxylase 1.

MicroRNAs (miRNAs) play a crucial role as oncogenic or tumor suppressors in the pathogenesis and progression of tumors. However, few studies have investigated the exact role of miR-4284 in renal cell carcinoma (RCC). We aimed to investigate the role of miR-4284 as a tumor suppressor in renal cancer cell lines. A498 and Caki-1 were transfected with miR-4284. The Cell Counting Kit-8, colony formation, apoptosis assays, and quantitative reverse transcription-polymerase chain reaction were used to evaluate tumor growth-inhibiting functions. The wound-healing, transwell, and sphere-formation assays were conducted to investigate tumorigenic characteristics. The potential target genes of miR-4284 were predicted and experimentally verified. A xenograft experiment was performed to estimate the tumor-growth-suppressive function of miR-4284. miR-4284 overexpression suppressed proliferation, induced apoptosis, and suppressed tumorigenic features of renal cancer cells. Glutamate decarboxylase 1 (GAD1) was directly targeted by miR-4284. A xenograft mouse model injected with Caki-1 cells transfected with miR-4284 showed significantly decreased tumor growth rate and volume. miR-4284 affected tumor growth, metastasis, and apoptosis of renal cancer cells in vitro and in vivo. These findings highlight the potential of miR-4284 as a target for anticancer miRNA therapeutics in RCC.

Effect of the Duration of NSAID Use on COVID-19.

Background and Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control pain and fever. However, their effect on COVID-19 infected patients has not been fully studied. In this study, we investigated the effect of the duration of NSAIDs use on COVID-19 infection and clinical outcomes. Materials and Methods: In South Korea, 25,739 eligible patients who received COVID-19 testing between 1 January and 31 July 2020, were included in this retrospective observational cohort analysis. Based on the date of the first COVID-19 test for each patient, NSAID prescription dates were used to separate patients into two groups (short-term group: <2 weeks; long-term group: 8−12 weeks). COVID-19 infectivity and clinical outcomes were analyzed. We used the propensity score-matching (PSM) method. Results: Of the 580 patients who had taken NSAIDs before the date of COVID-19 test, 534 and 46 patients were grouped in the short- and long-term NSAID-use groups, respectively. We did not find a statistically significant increased risk of COVID-19 infection (adjustment for age and sex, p = 0.413; adjustment for age, sex, region of residence, comorbidity, Charlson Comorbidity Index, and current use of medication, p = 0.259) or change in clinical outcomes, including conventional oxygen therapy, admission of intensive care unit, artificial ventilation, or death, between the two groups in which the PSM method was applied. Conclusions: The duration of NSAIDs use did not have a statistically significant effect on COVID-19 infectivity or clinical outcomes. However, further studies looking at clinical presentation and laboratory test results in a large number of people should be performed.

Frizzled3 inhibits Vangl2-Prickle3 association to establish planar cell polarity in the vertebrate neural plate.

The orientation of epithelial cells in the plane of the tissue, known as planar cell polarity (PCP), is regulated by interactions of asymmetrically localized PCP protein complexes. In the Xenopus neural plate, Van Gogh-like2 (Vangl2) and Prickle3 (Pk3) proteins form a complex at the anterior cell boundaries, but how this complex is regulated in vivo remains largely unknown. Here, we use proximity biotinylation and crosslinking approaches to show that Vangl2-Pk3 association is inhibited by Frizzled3 (Fz3, also known as Fzd3), a core PCP protein that is specifically expressed in the neuroectoderm and is essential for the establishment of PCP in this tissue. This inhibition required Fz3-dependent Vangl2 phosphorylaton. Consistent with our observations, the complex of Pk3 with nonphosphorylatable Vangl2 did not polarize in the neural plate. These findings provide evidence for in vivo regulation of Vangl2-Pk3 complex formation and localization by a Frizzled receptor.

Effects of observation of hand movements reflected in a mirror on cortical activation in patients with stroke.

[Purpose] The purpose of this study was to examine what changes occur in brain waves when patients with stroke receive mirror therapy intervention. [Subjects and Methods] The subjects of this study were 14 patients with stroke (6 females and 8 males). The subjects were assessed by measuring the alpha and beta waves of the EEG (QEEG-32 system CANS 3000). The mirror therapy intervention was delivered over the course of four weeks (a total of 20 sessions). [Results] Relative alpha power showed statistically significant differences in the F3, F4, O1, and O2 channels in the situation comparison and higher for hand observation than for mirror observation. Relative beta power showed statistically significant differences in the F3, F4, C3, and C4 channels. [Conclusion] This study analyzed activity of the brain in each area when patients with stroke observed movements reflected in a mirror, and future research on diverse tasks and stimuli to heighten activity of the brain should be carried out.

Action observation for upper limb function after stroke: evidence-based review of randomized controlled trials.

[Purpose] The purpose of this study was to suggest evidenced information about action observation to improve upper limb function after stroke. [Methods] A systematic review of randomized controlled trials involving adults aged 18 years or over and including descriptions of action observation for improving upper limb function was undertaken. Electronic databases were searched, including MEDLINE, CINAHL, and PEDro (the Physiotherapy Evidence Database), for articles published between 2000 to 2014. Following completion of the searches, two reviewers independently assessed the trials and extracted data using a data extraction form. The same two reviewers independently documented the methodological quality of the trials by using the PEDro scale. [Results] Five randomized controlled trials were ultimately included in this review, and four of them (80%) reported statistically significant effects for motor recovery of upper limb using action observation intervention in between groups. [Conclusion] This review of the literature presents evidence attesting to the benefits conferred on stroke patints resulting from participation in an action observation intervention. The body of literature in this field is growing steadily. Further work needs to be done to evaluate the evidence for different conditions after stroke and different duration of intervention.

Effect of purposeful action observation on upper extremity function in stroke patients.

[Purpose] The purpose of this study was to identify the effect of purposeful action observation on upper extremity function in patients with stroke. [Subjects and Methods] Twelve subjects were randomly to either the experimental group or control group. The experimental group underwent occupational therapy and a purposeful action observation program. The control group underwent occupational therapy and placebo treatment in which the subjects performed a purposeful action observation program without actually observing the purposeful actions. The Wolf Motor Function Test was used to measure upper extremity function before and after the intervention in both groups. [Results] Both the experimental and control groups demonstrated improved upper extremity function after the intervention, but there was no significant difference between groups. Compared with before the intervention, the experimental group showed significantly improved upper extremity function after the intervention. [Conclusion] Based on these results, a purposeful action observation program can improve upper extremity function in patients with stroke. In future research, more subjects should be included for evaluation of different treatments.

Virtual reality for cognitive rehabilitation after brain injury: a systematic review.

[Purpose] The purpose of this review was to investigate various types of VR programs and their use in cognitive evaluations and interventions for patients with brain injury. [Subjects and Methods] PubMed, Cochrane, and OTseeker electronic databases were searched with the search terms. At of 350 titles and abstracts were retrieved, and 17 articles were selected for this review. Selected articles were assessed on the level of evidence using the Physiotherapy Evidence Database (PEDro) scale. [Results] Articles assessing the impact of cognitive impairments in memory were most commonly found, and VR interventions elicited positive effects in patients with brain injury. [Conclusion] VR can be considered a new tool for cognitive rehabilitation after brain injury. VR interventions also have a number of advantages, e.g. cost-effectiveness, compared to other interventions.

The effect of mirror therapy on upper-extremity function and activities of daily living in stroke patients.

The purpose of this study was to examine the effects of mirror therapy on upper-extremity function and activities of daily living in chronic stroke patients. [Subjects and Methods] Fifteen subjects were each assigned to a mirror therapy group and a sham therapy group. The Fugl-Meyer Motor Function Assessment and the Box and Block Test were performed to compare paretic upper-extremity function and hand coordination abilities. The functional independence measurement was conducted to compare abilities to perform activities of daily living. [Results] Paretic upper-extremity function and hand coordination abilities were significantly different between the mirror therapy and sham therapy groups. Intervention in the mirror therapy group was more effective than in the sham therapy group for improving the ability to perform activities of daily living. Self-care showed statistically significant differences between the two groups. [Conclusion] Mirror therapy is effective in improving paretic upper-extremity function and activities of daily living in chronic stroke patients.

Effects of purposeful action observation on kinematic patterns of upper extremity in individuals with hemiplegia.

[Purpose] This study investigated the effects of purposeful action observation on upper extremity kinematic patterns in individuals with hemiplegia. [Subjects and Methods] Twelve patients were recruited in accordance with the inclusion criteria. The experimental group (n=6) was trained with a purposeful action observation program. The control group (n=6) was trained with only purposeful action without action observation. The programs were performed 30 min/session, 5 times per week for 30 sessions in 6 weeks of training. Upper extremity kinematic patterns were measured by a 3-dimensional motion analysis system before and after training, and the results were analyzed. [Results] The experimental group and the control group showed improvements in average velocity, trajectory ratio, and movement degree, but no statistically significant differences were observed between the groups. The experimental group showed statistically significant improvements in average velocity, trajectory ratio after the intervention. The experimental group also showed an improvement in movement degree, but the post-intervention difference was not significant. [Conclusion] The results of this study show that purposeful action observation training program improved the average velocity and trajectory ratio of stroke patients. Further research should enroll more subjects divided into more specific groups for treatment.

The effects of mirror therapy with tasks on upper extremity function and self-care in stroke patients.

[Purpose] The purpose of this study was to determine the effects of mirror therapy with tasks on upper extremity unction and self-care in stroke patients. [Subjects] Thirty participants were randomly assigned to either an experimental group (n=15) or a control group (n=15). [Methods] Subjects in the experimental group received mirror therapy with tasks, and those in the control group received a sham therapy; both therapies were administered, five times per week for six weeks. The main outcome measures were the Manual Function Test for the paralyzed upper limb and the Functional Independence Measure for self-care performance. [Results] The experimental group had more significant gains in change scores compared with the control group after the intervention. [Conclusion] We consider mirror therapy with tasks to be an effective form of intervention for upper extremity function and self-care in stroke patients.

Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling.

The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP) proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP) of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

The sul1 gene in Stenotrophomonas maltophilia with high-level resistance to trimethoprim/sulfamethoxazole.

Emerging resistance to trimethoprim/sulfamethoxazole (SXT) poses a serious threat to the treatment of Stenotrophomonas maltophilia infections. We determined the prevalence and molecular characteristics of acquired SXT resistance in recent clinical S. maltophilia isolates obtained from Korea. A total of 252 clinical isolates of S. maltophilia were collected from 10 university hospitals in Korea between 2009 and 2010. Antimicrobial susceptibility was determined by using the CLSI agar dilution method. The sul1, sul2, and sul3 genes, integrons, insertion sequence common region (ISCR) elements, and dfrA genes were detected using PCR. The presence of the sul1 gene and integrons was confirmed through sequence analysis. Among the 32 SXT-resistant isolates, sul1 was detected in 23 isolates (72%), all of which demonstrated high-level resistance (≥64 mg/L) to SXT. The sul1 gene (varying in size and structure) was linked to class 1 integrons in 15 of the 23 isolates (65%) harboring this gene. None of the SXT-susceptible isolates or the SXT-resistant isolates with a minimum inhibitory concentration of 4 and 8 mg/L were positive for sul1. Moreover, the sul2, sul3, and dfrA genes or the ISCR elements were not detected. The sul1 gene may play an important role in the high-level SXT resistance observed in S. maltophilia.

Neural crest specification by inhibition of the ROCK/Myosin II pathway.

Neural crest is a population of multipotent progenitor cells that form at the border of neural and non-neural ectoderm in vertebrate embryos, and undergo epithelial-mesenchymal transition and migration. According to the traditional view, the neural crest is specified in early embryos by signaling molecules including BMP, FGF, and Wnt proteins. Here, we identify a novel signaling pathway leading to neural crest specification, which involves Rho-associated kinase (ROCK) and its downstream target nonmuscle Myosin II. We show that ROCK inhibitors promote differentiation of human embryonic stem cells (hESCs) into neural crest-like progenitors (NCPs) that are characterized by specific molecular markers and ability to differentiate into multiple cell types, including neurons, chondrocytes, osteocytes, and smooth muscle cells. Moreover, inhibition of Myosin II was sufficient for generating NCPs at high efficiency. Whereas Myosin II has been previously implicated in the self-renewal and survival of hESCs, we demonstrate its role in neural crest development during ESC differentiation. Inhibition of this pathway in Xenopus embryos expanded neural crest in vivo, further indicating that neural crest specification is controlled by ROCK-dependent Myosin II activity. We propose that changes in cell morphology in response to ROCK and Myosin II inhibition initiate mechanical signaling leading to neural crest fates.

Effects of Cervical Flexion on the Flexion-relaxation Ratio during Smartphone Use.

[Purpose] The purpose of this study was to measure the cervical flexion-relaxation ratio (FRR) and intensity of neck pain and identify the differences according to postures adopted while using smartphones. [Subjects] Fifteen healthy adults with no neck pain, spinal trauma, or history cervical surgery participated in this study. [Methods] The activity of the cervical erector spinae muscle was recorded while performing a standardized cervical flexion-extension movement in three phases (flexion, sustained full flexion, extension). And neck pain intensity was recorded using a visual analog scale (VAS) with values between 0 and 10. Postures held while using a smartphone are distinguished between desk postures and lap postures. The FRR was calculated by dividing the maximal muscle activation during the extension phase by average activation during the complete flexion phase. [Results] No significant differences were found in the FRR between desk posture, lap posture, and baseline, though the intensity of the neck pain increased in the lap posture. [Conclusion] The FRR could be a significant criterion of neuromuscular impairment in chronic neck pain or lumbar pain patients, but it is impossible to distinguish neck pain that is caused by performing task for a short time. Prolonged lap posture might cause neck pain, so the use of smartphones for a long time in this posture should be avoided.

Role of Rab11 in planar cell polarity and apical constriction during vertebrate neural tube closure.

Epithelial folding is a critical process underlying many morphogenetic events including vertebrate neural tube closure, however, its spatial regulation is largely unknown. Here we show that during neural tube formation Rab11-positive recycling endosomes acquire bilaterally symmetric distribution in the Xenopus neural plate, being enriched at medial apical cell junctions. This mediolateral polarization was under the control of planar cell polarity (PCP) signalling, was necessary for neural plate folding and was accompanied by the polarization of the exocyst component Sec15. Our further experiments demonstrate that similar PCP-dependent polarization of Rab11 is essential for ectopic apical constriction driven by the actin-binding protein Shroom and during embryonic wound repair. We propose that anisotropic membrane trafficking has key roles in diverse morphogenetic behaviours of individual cells and propagates in a tissue by a common mechanism that involves PCP.

First outbreak of KPC-2-producing Klebsiella pneumoniae sequence type 258 in a hospital in South Korea.

In this study, we report the first outbreak of KPC-2-producing Klebsiella pneumoniae isolates from three patients admitted to a neurosurgery department in a South Korean teaching hospital. Multilocus sequence typing showed that the isolates were identical to the previous KPC producers in South Korea and other countries, suggesting clonal spread.

A hippotherapy simulator is effective to shift weight bearing toward the affected side during gait in patients with stroke.

AIM: We investigated whether a hippotherapy simulator has influence on symmetric body weight bearing during gait in patients with stroke. METHOD: Stroke patients were divided into a control group (n = 10) that received conventional rehabilitation for 60 min/day, 5 times/week for 4 weeks and an experimental group (n = 10) that used a hippotherapy simulator for 15 min/day, 5 times/week for 4 weeks after conventional rehabilitation for 45 min/day. Temporospatial gait assessed using OptoGait and trunk muscles (abdominis and erector spinae on affected side) activity evaluated using surface electromyography during sit-to-stand and gait. Prior to starting the experiment, pre-testing was performed. At the end of the 4-week intervention, we performed post-testing. RESULT: Activation of the erector spinae in the experimental group was significantly increased compared to that in the control group (p < 0.01), whereas activation of the rectus abdominis decreased during sit-to-stand. Of the gait parameters, load response, single support, total double support, and pre-swing showed significant changes in the experimental group with a hippotherapy simulator compared to control group (p < 0.05). Moreover, activation of the erector spinae and rectus abdominis in gait correlate with changes of gait parameters including load response, single support, total double support, and pre-swing in experimental group. CONCLUSION: These findings suggest that use of a hippotherapy simulator to patients with stroke can improve asymmetric weight bearing by influencing trunk muscles.

Effect of Wrist Joint Restriction on Forearm and Shoulder Movement during Upper Extremity Functional Activities.

[Purpose] This study measured %isolation and investigated whether it shows a difference between the presence and absence of wrist joint restriction, as well as changes in muscle activity patterns. [Methods] Twenty subjects performed upper extremity functional movement in the Manual Function Test (MFT) with and without wrist restriction, and the muscle activities of the trapezius, middle deltoid, biceps brachii, triceps brachii, extensor carpi radialis, and flexor carpi radialis were recorded. When there were differences in muscle activation, %isolation was implemented and the changes in the muscle activity patterns were noted. [Results] In the grasping and pinching tasks, there was a significant increase in %isolation of the upper trapezius and a significant decrease in %isolation of the extensor carpi radialis. Carrying a cube task, %isolation of the upper trapezius and middle deltoid significantly increased, whereas %isolation of the triceps brachii and extensor carpi radialis significantly decreased. In the pegboard task, the %isolation values of the extensor carpi radialis and flexor carpi radialis significantly decreased. [Conclusion] The data of this study should be useful for therapists, who can employ the information as material for the education and treatment of patients with wrist joint restriction. Therapists may thus look for ways to improve the quality of mobility by predicting the complement mobility depending on the activity performed and then determine whether to facilitate or restrict mobility.

CEP90 is required for the assembly and centrosomal accumulation of centriolar satellites, which is essential for primary cilia formation.

Centriolar satellites are PCM-1-positive granules surrounding centrosomes. Proposed functions of the centriolar satellites include protein targeting to the centrosome, as well as communication between the centrosome and surrounding cytoplasm. CEP90 is a centriolar satellite protein that is critical for spindle pole integrity in mitotic cells. In this study, we examined the biological functions of CEP90 in interphase cells. CEP90 physically interacts with PCM-1 at centriolar satellites, and this interaction is essential for centrosomal accumulation of the centriolar satellites and eventually for primary cilia formation. CEP90 is also required for BBS4 loading on centriolar satellites and its localization in primary cilia. Our results imply that the assembly and transport of centriolar satellites are critical steps for primary cilia formation and ciliary protein recruitment.

Multiplex PCR for rapid detection of genes encoding class A carbapenemases.

In recent years, there have been increasing reports of KPC-producing Klebsiella pneumoniae in Korea. The modified Hodge test can be used as a phenotypic screening test for class A carbapenamase (CAC)-producing clinical isolates; however, it does not distinguish between carbapenemase types. The confirmation of type of CAC is important to ensure optimal therapy and to prevent transmission. This study applied a novel multiplex PCR assay to detect and differentiate CAC genes in a single reaction. Four primer pairs were designed to amplify fragments encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR detected all genes tested for 4 CAC families that could be differentiated by fragment size according to gene type. This multiplex PCR offers a simple and useful approach for detecting and distinguishing CAC genes in carbapenem-resistant strains that are metallo-ß-lactamase nonproducers.