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Reference materials are essential for the quality assurance of molecular detection methods. We developed and characterized synthetic norovirus GI and GII RNA reference materials.Norovirus GI and GII RNA sequences including the ORF1-ORF2 junction region were designed based on 1,495 reported norovirus sequences and synthesized via plasmid preparation andThe synthetic norovirus GI and GII RNAs were positively detected using the six commercial norovirus detection kits and were homogeneous and stable for one year when stored at -20°C or -70°C. All data from the five laboratories were within a range of 1.0 log copies/μL difference for each RNA, and the overall mean concentrations for norovirus GI and GII RNAs were 7.90 log copies/μL and 6.96 log copies/μL, respectively.The synthetic norovirus GI and GII RNAs are adequate for quality control based on commercial molecular detection reagents for noroviruses with high sequence variability. The synthetic RNAs can be used as reference materials in norovirus molecular detection methods.

BACKGROUND: Neurodevelopmental treatment (NDT) and dynamic core-postural chain stabilization (DCS)- based exercise is effective for improving core stability and postural control in stroke patients. However, no study has reported respiratory function, increased fatigue and ADL function in subacute stroke patients by training using NDT and DCS exercises. OBJECTIVE: To compare the effects of DCS and NDT exercises on respiratory function, fatigue and activities of daily living in individuals with hemiparetic stroke. METHODS: Thirty-one participants with hemiparetic stroke (17 male, 14 female; mean age 60.4±14.58 years; post-stroke duration, 7.2±2.2 weeks) participated in this study. The participants were randomly allocated into DCS (n = 16) and NDT (n = 15). Respiratory function was determined using forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). The fatigue severity scale (FSS) and functional independent measure (FIM) were used to evaluate fatigue severity and activities of daily living (ADL). Analysis of covariance (ANCOVA) was used to evaluate post-test differences in the DCS and NDT exercise groups. RESULTS: ANCOVA revealed the superior effects of DCS in respiratory function, as well as clinical FSS and FIM tests, compared with those of NDT (p

Summary We report the implantation of patient-derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in a patient with idiop...

Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of striatal dopamine, secondary to degeneration of midbrain dopamine (mDA) neurons in the substantia nigra, rendering cell transplantation a promising therapeutic strategy. To establish human induced pluripotent stem cell-based (hiPSC-based) autologous cell therapy, we report a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, we developed a method to more efficiently generate clinical-grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, we established a "spotting"-based in vitro differentiation methodology to generate functional and healthy mDA cells in a scalable manner. Third, we developed a chemical method that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restores motor function and reinnervates host brain, while showing no evidence of tumor formation or redistribution of the implanted cells. We propose that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.

Background: Knee osteoarthritis (OA) is a single most arthritic disease. Knee joint space width (JSW) is commonly used for grading severity of knee OA. However, previous studies did not established criterion validity and test-retest reliability of ultrasound (US) image for measuring JSW. Objects: The aim of this study was to establish criterion validity and test-retest reliability of US measurement of medial and lateral knee JSW. Methods: Twenty-nine subjects with knee OA were participated. The US and X-ray were used to measure knee JSW. One sample Kolmogorov-Smirnov test was used to confirm the data normal distribution. Pearson correlation coefficient and ICC were used to calculated and establish criterion validity and test-retest reliability, respectively. Results: US measurement of medial and lateral knee JSW was highly correlated with radiographic imaging measure (r=.714 and .704, respectively). Test-retest reliabilities of medial and lateral knee JSW were excellent correlated (ICC=.959 for medial side and .988 for lateral side, respectively). Conclusion: US may be valid tool to measure knee JSW.

The aim of this study is to develop a novel method for the accurate diagnosis of the infection status of viral diseases, which requires discriminated and quantitative detection of different anti-virus immunoglubulin subtypes. Considering hepatitis A as a representative model disease, viral antigen nanoparticles (vAgNPs) were designed and synthesized by genetically presenting hepatitis A virus (HAV) antigens on the surface of human heavy chain ferritin (hFTH) nanoparticles to detect anti-HAV antibodies with discriminating immunoglobulin subtypes M and G (IgM and IgG, respectively). The vAgNPs also display multi-copies of hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is vital for the autonomous generation of quantitatively meaningful detection signals. The quantitative level of anti-HAV IgM or IgG in 30 patient sera was successfully analyzed using the vAgNPs of HAV, which was performed through label-free one-step-immunoassay based on the self-enhancement of optical signals from gold nanoparticles clustered on the viral antigen nanoparticles. The diagnostic performance was compared with that of enzyme-linked immunosorbent assay (ELISA), which did not enable accurate quantitative assay due to the poor linearity between the antibody concentration and detection signal. Furthermore, these vAgNP-based immunoassays did not produce any false negative/positive signals, indicating 100% sensitivity and 100% specificity.

Induced pluripotent stem cell (iPSC) technology that could revert the fate of terminally differentiated somatic cells into embryonic stem cell–like status by using ectopic expression of four transcription factors (e.g., Oct4, Sox2, Klf4, and c-Myc) opened up a new era of stem cell research to study and treat intractable human diseases, including neurodegenerative disorders such as Parkinson’s and Huntington’s diseases. Nevertheless, our current understanding of the reprogramming process is incomplete and requires further investigation into the underlying mechanisms and development of optimal reprogramming techniques. In this chapter, we provide an overview of the current techniques and critical issues for further optimization of high-quality iPSC generation.

Background Neurodevelopmental treatment (NDT) and Dynamic neuromuscular stabilization (DNS)-based exercise is effective for improving core stability and postural control in stroke patients. Objective To compare the effects of DNS and conventional NDT exercises on diaphragm movement, abdominal muscle thickness, and postural control in stroke patients. Methods The participants were randomly allocated into DNS (n = 16) and NDT (n = 15) for 30 minutes each per day, 3 days a week for 4 weeks. Diaphragm movement and abdominal muscle thickness were determined using ultrasonography. The trunk impairment scale (TIS) and Berg Balance Scale (BBS) were used to measure postural control. The functional ambulation category (FAC) was used to evaluate gait ability. Analysis of covariance (ANCOVA) was used to evaluate post-test differences in the DNS and NDT exercise groups. Results ANCOVA revealed the superior effects of DNS in diaphragm movement and abdominal muscle thickness (transversus abdominis, internal oblique), as well as clinical BBS and FAC tests, compared with those of NDT (p Conclusions This novel clinical trial suggests that DNS training was more effective than NDT training in improving postural movement control and gait ability via a balanced co-activation of the diaphragm and TrA/IO in stroke patients.

Background: We developed a novel integrative lumbar stabilization technique that combines lumbar extension (LE) exercise with abdominal drawing-in maneuver (ADIM) to ameliorate low back pain (LBP) associated with neuromuscular imbalance and instability, based on the collective evidence of contemporary spinal rehabilitation. Objects: The specific aim of the present study was to investigate the effects of LE exercise with and without ADIM on core muscle strength, lumbar spinal instability, and pain, as well as functional characteristics in individuals with LBP using advanced radiographic imaging techniques. Methods: patients with mechanical LBP (N = 40, 6 males; 35.1±7.6 years) were recruited and randomly assigned either to the combined LE and ADIM (experimental group) or the LE alone (control group). Outcome measures included the visual analog scale, the modified Oswestry Disability Index, muscle strength imbalance (MSI), and radiographic imaging. The lumbar intervertebral displacement (LID), intervertebral (IV) and total lumbar extension (TLE) angles were calculated to evaluate the lumbar segmental instability. Results: The experimental group showed significant differences in the L3-L4, L5-S1 LIDs, L4-L5 and L5-S1 IV angles, and TLE angle as compared to the controls (p

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed world ages, this creates an escalating burden on society both in economic terms and in quality of life for these patients and for the families that support them. Although currently available pharmacological or surgical treatments may significantly improve the quality of life of many patients with PD, these are symptomatic treatments that do not slow or stop the progressive course of the disease. Because motor impairments in PD largely result from loss of midbrain dopamine neurons in the substantia nigra pars compacta, PD has long been considered to be one of the most promising target diseases for cell-based therapy. Indeed, numerous clinical and preclinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells as a standardized therapeutic regimen has been fraught with fundamental ethical, practical, and clinical issues, prompting scientists to explore alternative cell sources. Based on groundbreaking establishments of human embryonic stem cells and induced pluripotent stem cells, these human pluripotent stem cells have been the subject of extensive research, leading to tremendous advancement in our understanding of these novel classes of stem cells and promising great potential for regenerative medicine. In this review, we discuss the prospects and challenges of human pluripotent stem cell-based cell therapy for PD.

BACKGROUND The robotic-assisted gait training (RAGT) system has gained recognition as an innovative, effective paradigm to improve functional ambulation and activities of daily living in spinal cord injury and stroke. However, the effects of the Walkbot robotic-assisted gait training system with a specialized hip-knee-ankle actuator have never been examined in the paraplegia and quadriplegia population. OBJECTIVE The aim of this study was to determine the long-term effects of Walkbot training on clinical for hips and knee stiffness in individuals with paraplegia or quadriplegia. METHODS Nine adults with subacute or chronic paraplegia resulting from spinal cord injury or quadriplegia resulting from cerebral vascular accident (CVA) and/or hypoxia underwent progressive conventional gait retraining combined with the Walkbot RAGT for 5 days/week over an average of 43 sessions for 8 weeks. Clinical outcomes were measured with the Functional Ambulation Category (FAC), Modified Rankin Scale (MRS), Korean version of the Modified Barthel Index (K-MBI), Modified Ashworth Scale (MAS). Kinetic and kinematic data were collected via a built-in Walkbot program. RESULTS Wilcoxon signed-rank tests showed significant positive intervention effects on K-MBI, maximal hip flexion and extension, maximal knee flexion, active torque in the knee joint, resistive torque, and stiffness in the hip joint (P < 0.05). These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. These improvements were associated with functional recovery in gait, balance, mobility and daily activities. CONCLUSIONS These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. This is the first clinical evidence for intensive, long-term effects of the Walkbot RAGT on active or resistive moments and stiffness associated with spasticity and functional mobility in individuals with subacute or chronic paraplegia or quadriplegia who had reached a plateau in motor recovery after conventional therapy.

The objective of this study is to develop an accurate, rapid, simple, and label-free assay technology that enables point-of-care diagnosis of AIDS. For this, 3-dimensional (3D) probes to sensitively detect anti-HIV antibodies were designed and synthesized by genetically presenting a HIV antigen (gp41) on the surface of engineered human ferritin nanoparticles. The 3D probes also present multi-copies of the hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is essential for the generation and self-enhancement of assay signals. The developed new assay technology (named “one-step-immunoassay”) quickly produced clear optical signals through a simple and convenient one-step procedure. The diagnostic performance of the one-step-immunoassay was compared with that of the conventional lateral flow assay (LFA) using 30 AIDS patient and 20 healthy sera. The sensitivity of LFA was only 63% when a single antigen (gp41) was used but enhanced to 90% when three different antigens (gp41, p24, and gp120) were used together as the assay probes. In contrast, the one-step-immunoassay using only gp41 produced strong optical signals within 15 min without causing any false negative/positive signals, showing 100% sensitivity and 100% specificity and holding promising potential for clinical point-of-care diagnosis of AIDS.

PURPOSE To determine the effects of a novel dynamic neuromuscular stabilization (DNS) technique on gross motor function, diaphragm movement, and activation of the external oblique (EO) and internal oblique (IO)/transversus abdominal (TrA) muscles in participants with cerebral palsy (CP). METHOD Fifteen participants with CP (7 females) underwent DNS intervention for 30 minutes/day, 3 days a week for 4 weeks. Gross motor function, diaphragm movement, and muscle activation were determined using a gross motor function measure (GMFM-88), ultrasound, and electromyography measurements, respectively, before and after the DNS core stabilization intervention. Paired t-tests were used at p

BACKGROUND Core stabilization plays an important role in the regulation of postural stability. To overcome shortcomings associated with pain and severe core instability during conventional core stabilization tests, we recently developed the dynamic neuromuscular stabilization-based heel sliding (DNS-HS) test. OBJECTIVE The purpose of this study was to establish the criterion validity and test-retest reliability of the novel DNS-HS test. METHOD Twenty young adults with core instability completed both the bilateral straight leg lowering test (BSLLT) and DNS-HS test for the criterion validity study and repeated the DNS-HS test for the test-retest reliability study. Criterion validity was determined by comparing hip joint angle data that were obtained from BSLLT and DNS-HS measures. The test-retest reliability was determined by comparing hip joint angle data. RESULTS Criterion validity was (ICC2,3) = 0.700 (p< 0.05), suggesting a good relationship between the two core stability measures. Test-retest reliability was (ICC3,3) = 0.953 (p< 0.05), indicating excellent consistency between the repeated DNS-HS measurements. CONCLUSIONS Criterion validity data demonstrated a good relationship between the gold standard BSLLT and DNS-HS core stability measures. Test-retest reliability data suggests that DNS-HS core stability was a reliable test for core stability. Clinically, the DNS-HS test is useful to objectively quantify core instability and allow early detection and evaluation.

Background: Anti-hepatitis C virus antibody (anti-HCV) assays are recommended for screening HCV-infected persons. The VIDAS Anti-HCV Assay (bioMerieux, France), based on the enzyme-linked fluorescence test principle, was recently introduced in Korea. We evaluated the clinical performance of the VIDAS assay. Methods: One hundred HCV-positive and 1,002 HCV-negative blood samples confirmed by Architect anti-HCV (Abbott Laboratories, USA) and COBAS TaqMan HCV real-time PCR (Roche Diagnostics, USA) or the Procleix Ultrio Plus Assay (Gen-Probe Incorporated, USA) were obtained from the Human Serum Bank (HSB) and tested by VIDAS. In case of discrepant results, we conducted a recombinant immunoblot assay (RIBA). Results: The agreement rates for known HCV-positive and HCV-negative samples between the VIDAS assay and the HSB testing were 100% (95% confidence interval [CI]: 96.4-100%) and 99.5% (95% CI: 98.8-99.8%), respectively. One of the five discrepant samples was positive for Core 2+ and NS3-2 2+ reactivity, two samples were negative, and the other two were indeterminate regarding NS4 2+ reactivity in RIBA. We observed a significant but weak positive correlation between the titers of VIDAS and Architect assays (r=0.315, P

Gross motion of the ankle joint complex (AJC) is a summation of the ankle and subtalar joints. Although AJC kinematics have been widely used to evaluate the function of the AJC, the coordinated movements of the ankle and subtalar joints are not well understood. The purpose of this study was to accurately quantify the individual kinematics of the ankle and subtalar joints in the intact foot during ground walking by using a bi-planar fluoroscopic system. Bi-planar fluoroscopic images of the foot and ankle during walking and standing were acquired from 10 healthy subjects. The three-dimensional movements of the tibia, talus, and calcaneus were calculated with a three-dimensional/two-dimensional registration method. The skeletal kinematics were quantified from 9% to 86% of the full stance phase because of the limited camera speed of the X-ray system. At the beginning of terminal stance, plantar-flexion of the AJC was initiated in the subtalar joint on average at 75% ranging from 62% to 76% of the stance phase, and plantar-flexion of the ankle joint did not start until 86% of the stance phase. The earlier change to plantar-flexion in the AJC than the ankle joint due to the early plantar-flexion in the subtalar joint was observed in 8 of the 10 subjects. This phenomenon could be explained by the absence of direct muscle insertion on the talus. Preceding subtalar plantar-flexion could contribute to efficient and stable ankle plantar-flexion by locking the midtarsal joint, but this explanation needs further investigation.

A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function.

Background The purpose of the present study was to compare therapeutic effects of an electromyography (EMG) biofeedback augmented by virtual reality (VR) and EMG biofeedback alone on the triceps and biceps (T:B) muscle activity imbalance and elbow joint movement coordination during a reaching motor taskOBJECTIVE: To compare therapeutic effects of an electromyography (EMG) biofeedback augmented by virtual reality (VR) and EMG biofeedback alone on the triceps and biceps muscle activity imbalance and elbow joint movement coordination during a reaching motor task in normal children and children with spastic cerebral palsy (CP). Methods 18 children with spastic CP (2 females; mean±standard deviation = 9.5 ± 1.96 years) and 8 normal children (3 females; mean ± standard deviation = 9.75 ± 2.55 years) were recruited from a local community center. All children with CP first underwent one intensive session of EMG feedback (30 minutes), followed by one session of the EMG-VR feedback (30 minutes) after a 1-week washout period. Clinical tests included elbow extension range of motion (ROM), biceps muscle strength, and box and block test. EMG triceps and biceps (T:B) muscle activity imbalance and reaching movement acceleration coordination were concurrently determined by EMG and 3-axis accelerometer measurements respectively. Independent t-test and one-way repeated analysis of variance (ANOVA) were performed at p Results The one-way repeated ANOVA was revealed to be significantly effective in elbow extension ROM (p = 0.01), biceps muscle strength (p = 0.01), and box and block test (p = 0.03). The one-way repeated ANOVA also revealed to be significantly effective in the peak triceps muscle activity (p = 0.01). However, one-way repeated ANOVA produced no statistical significance in the composite 3-dimensional movement acceleration coordination data (p = 0.12). Conclusions The present study is a first clinical trial that demonstrated the superior benefits of the EMG biofeedback when augmented by virtual reality exercise games in children with spastic CP. The augmented EMG and VR feedback produced better neuromuscular balance control in the elbow joint than the EMG biofeedback alone.

We systematically reviewed randomised controlled trials of the i-gel® vs different types of laryngeal mask airway in children. We included nine studies. There was no evidence for differences in: rate of insertion at first attempt; insertion time; ease of insertion; or gastric tube insertion. The mean (95% CI) oropharyngeal leak pressure was 3.29 (2.25-4.34) cmH2 O higher with the i-gel, p < 0.00001. The relative rate (95% CI) of a good fibreoptic view through the i-gel was 1.10 (1.01-1.19), p = 0.02. There were no significant differences in the rates of complications, except for blood on the airway, relative rate with the i-gel 0.46 (0.23-0.91), p = 0.02. We concluded that the clinical performance of the i-gel and LMA was similar, except for three outcomes that favoured the i-gel.

Background Our goal was to enhance the productivity of phlebotomists and reduce outpatient wait times. Here, we aimed to develop a computer simulation program in which resources would be shifted from the laboratory to assist with phlebotomy. We evaluated the efficacy of computer simulation approaches for phlebotomy wait time and provide phlebotomy help time. Methods We evaluated the performance of the following three approaches: no helping system (NHS), the conventional assistance system (CAS), and the computer simulated helping system (CSHS). The CSHS predicted the phlebotomy waiting times based on computer simulation approaches, decided the assist times, and sounded an alarm. Results The wait time for the NHS was significantly longer than that of the CAS and the CSHS (P 10 min. Significant differences between the three systems were detected (P < 0.05). The phlebotomy computer simulation system significantly decreased the help time of the phlebotomists (CAS was 93.3 ± 19.7 min vs. CSHS was 79.5 ± 17.7 min, P = 0.03). Conclusion We designed a computer-based predicted alarm system. This system could effectively decrease help time for phlebotomists and outpatients phlebotomy wait times.

Tcea3 is present in high concentrations in mouse embryonic stem cells (mESCs) and functions to activate Lefty1, a negative regulator of Nodal signaling. The Nodal pathway has numerous biological activities, including mesoderm induction and patterning in early embryogenesis. Here, we demonstrate that the suppression of Tcea3 in mESCs shifts the cells from pluripotency into enhanced mesoderm development. Vascular endothelial growth factor A (VEGFA) and VEGFC, major transcription factors that regulate vasculogenesis, are activated in Tcea3 knocked down (Tcea3 KD) mESCs. Moreover, differentiating Tcea3 KD mESCs have perturbed gene expression profiles with suppressed ectoderm and activated mesoderm lineage markers. Most early differentiating Tcea3 KD cells expressed Brachyury-T, a mesoderm marker, whereas control cells did not express the gene. Finally, development of chimeric embryos that included Tcea3 KD mESCs was perturbed.

Highlights • The new real-time quantitative PCR system for hepatitis B virus was evaluated. • This system showed satisfactory analytical sensitivity, excellent reproducibility, no cross-reactivity, no interference and high correlation with other real-time PCR assays. • The assay is a useful tool for the detection and monitoring of hepatitis B virus infection., The performance of a recently developed real-time PCR system, the ExiStation HBV diagnostic system, for quantitation of hepatitis B virus (HBV) in human blood was evaluated. The detection limit, reproducibility, cross-reactivity, and interference were evaluated as measures of analytical performance. For the comparison study, 100 HBV-positive blood samples and 100 HBV-negative samples from Korean Blood Bank Serum were used, and the results of the ExiStation HBV system showed good correlation with those obtained using the Cobas TaqMan (r2 = 0.9931) and Abbott real-time PCR systems (r2 = 0.9894). The lower limit of detection was measured as 9.55 IU/mL using WHO standards and the dynamic range was linear from 6.68 to 6.68 × 109 IU/mL using cloned plasmids. The within-run coefficient of variation (CV) was 9.4%, 2.1%, and 1.1%, and the total CV was 11.8%, 3.6%, and 1.7% at a concentration of 1.92 log10 IU/mL, 3.88 log10 IU/mL, and 6.84 log10 IU/mL, respectively. No cross-reactivity or interference was detected. The ExiStation HBV diagnostic system showed satisfactory analytical sensitivity, excellent reproducibility, no cross-reactivity, no interference, and high agreement with the Cobas TaqMan and Abbott real-time PCR systems, and is therefore a useful tool for the detection and monitoring of HBV infection.

TFIIS is a transcription elongation factor conserved in frog, mouse and human. Recently, knockdown of TCEA1, the most well-characterized isoform of TFIIS, by RNA silencing was reported to inhibit cancer cell proliferation and induce apoptosis in breast, lung and pancreatic cancer cell lines through activation of p53 (Hubbard et al., 2008 [1]). However, the functions of other TFIIS isoforms are poorly defined. The present study shows that TCEA3, an isoform of TFIIS, can trigger ovarian cancer-specific cell death by activating the JNK signaling pathway. TCEA3 expression is low in ovarian cancer cell lines compared to noncancerous ovarian epithelial cells. Suppression of TCEA3 in noncancerous ovarian epithelial cells promotes cell growth whereas ectopic expression of TCEA3 in ovarian cancer cell lines induces the caspase-dependent mitochondrial cell death pathway. Molecular and chemical inhibition assays show that the interaction of TCEA3 with TGFβ receptor I induces cell death in ovarian cancer cell through Smad-independent activation of the JNK pathway. These results reveal that TCEA3 induces a novel apoptotic mechanism in OEC, which provides TCEA3 as a novel target to develop therapeutics of ovarian cancer.

6, Gwacheon, Korea Background: A reliable rapid assay for hepatitis C virus (HCV) may be helpful in various clinical settings. We evaluated the performance of the OraQuick HCV Rapid Antibody Test (OraSure Technologies Inc., Bethlehem, PA, USA). Methods: Clinical sensitivity and specifi city were evaluated with oral fl uids and sera from 137 patients diagnosed with hepatitis C and 300 healthy blood donors in a multi-center collaborative study. The stored sera of 200 proven HCV-infected patients and 200 healthy subjects were also evaluated. Analytical sensitivity was estimated with 4 commercial seroconversion panels and 7 Korean reference panels. The performance of 4 laboratory-based tests (3 chemiluminescence assays and 1 enzyme immunoassay) and 4 rapid test kits was compared. We also assessed the interference due to bilirubin, hemoglobin, lipid, rheumatoid factor, multipara, and several viral infections. Results: The clinical sensitivity and specifi city of the OraQuick HCV test using oral fl uid were 97.8% (95% confi dence interval [CI], 93.2-99.4%) and 100% (95% CI, 98.4-100%), respectively. The clinical sensitivity using serum samples was 100%. Using the 4 seroconversion panels, the OraQuick HCV test showed results comparable to those of the laboratory-based assays; its analytical sensitivity was higher than that of the other rapid test kits. There was no cross-reactivity with common interfering factors. Conclusions: The clinical performance of the OraQuick HCV Test is comparable to that of laboratory-based tests with both serum and oral fl uid. This supports the supplementary use of rapid HCV testing using oral fl uid in various medical and non-medical settings.

Malignant gliomas are the most common primary brain tumor in adults. A number of genes have been impli- cated in glioblastoma including mutation and deletion of PTEN. PTEN is a regulator of PI3K-mediated Akt signaling pathways and has been recognized as a therapeutic target in glioblastoma. To achieve potent therapeutic inhibition of the PI3K-Akt pathway in glioblastoma, it is essential to under- stand the interplay between the regulators of its activation. Here, ectopic expression of PTEN in the U-87MG human glioblastoma-astrocytoma cell line is shown to result in the depletion of glioblastoma stem cells (GSCs) and to cause growth retardation and senescence. These effects are likely to be associated with PTEN-mediated cooperative perturba- tion of Akt and Stat3 signals. Using an in vivo rat model of glioblastoma, we showed that PTEN-overexpressing U-87MG cells failed to induce tumor formation, while untreated U-87MG cells did so. Furthermore, cells expressing the phos- phorylated form of Stat3 were completely absent from the brain of rats implanted with PTEN-overexpressing U-87MG cells. Based on these results, PTEN appears to function as a crucial inhibitor of GSCs and as an inducer of senescence, suggesting that functional enhancement of the PTEN pathway will be useful to provide a therapeutic strategy for targeting glioblastoma.

Background The purpose of this study was to evaluate the analgesic effect of Rubus occidentalis extract (ROE) in a rat model of incisional pain. The involved mechanisms and proinflammatory cytokine response were also examined. Materials and methods To investigate the analgesic effect, rats were intraperitoneally administered with normal saline or various doses of ROE before or after a plantar incision. To evaluate the involved mechanism, rats were intraperitoneally administered yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine after a plantar incision; ROE was then administered intraperitoneally. The mechanical withdrawal threshold (MWT) was tested with von Frey filaments at various time points. To determine the inflammatory response, serum levels of interleukin (IL)-1β or IL-6 were measured. Results The MWTs significantly increased at 15 min after postincisional administration of 300 mg/kg ROE when compared with those in the control group. This elevation was observed for up to 45 min. Overall, MWTs increased in proportion to ROE dosage; however, ROEs administered before the incision produced no significant change in the MWT. The analgesic effect of ROE was significantly antagonized by mecamylamine, naloxone, and yohimbine, and agonized by dexmedetomidine. Administration of ROE inhibited the postincisional increase in serum IL-1β and IL-6. Conclusions Intraperitoneal administration of ROE after surgery induces antinociceptive effects in a rat model of postoperative pain, and its effects on mechanical hyperalgesia may be associated with α 2 -adrenergic, nicotinic cholinergic, and opioid receptors.

Background: Dynamic postural instability is a common neuromuscular impairment in cerebral palsy (CP), which often includes balance dysfunction and an associated risk of serious falls. Robotic hippotherapy has recently become a widespread clinical application to facilitate postural core stabilization, strength, and endurance through repetitive vestibular and proprioceptive stimulation to the spine via the sensorimotor system pathways. However, the long-term effects of robotic hippotherapy on dynamic postural instability in CP remain unclear. Objective: To examine the long-term effects of robotic hippotherapy on dynamic postural stability in CP. Methods: An advanced three-dimensional biomechanical eight-camera video motion capture (VMC) system was used to compute the center of mass (COM) pathway, which represents intervention-related spinal core instability. The robotic hippotherapy system was used to improve dynamic postural stability and associated balance performance. Robotic hippotherapy exercise was provided for 45 minutes/session, 2-3 times a week over the 12-week period. Results: Abnormal mean COM pathway length, standard deviation, and range substantially decreased after 12 weeks of robotic hippotherapy. The initial x-axis COM was greater than that of the y-axis. However, the amount of abnormal anterior-posterior and medio-lateral postural sway substantially decreased after robotic hippotherapy. Conclusions: This study provides the first compelling evidence that the robotic hippotherapy is safe and effective for postural instability control and sitting balance dysfunction that mitigates the risk of falls in CP.

The development of a prophylactic vaccine that targets human papillomaviruses (HPV) 6, 11, 16, and 18 to prevent cervical cancer has increased interest in the ethnic and geographical distributions of HPV genotypes. We investigated HPV prevalence and type distribution by restriction fragment mass polymorphism (RFMP) testing a total of 60,775 specimens (aged 18-79 yr, median 44) taken from liquid-based cytology. Overall HPV positive rate of total patients was 34.2%. Among the positive patients, 87.7% was single type infections, and 12.3% was multiple HPV types. HPV-16 was the most prevalent genotype observed in 2,307 (26.0%), followed by type 52 in 2,269 (25.5%), type 58 in 1,090 (12.3%), type 18 in 633 (7.1%), type 56 in 436 (4.9%). The pattern of high risk-HPV positive rate according to age showed U-shape with a peak in HPV prevalence among women less than 30 yr of age, and a second peak among the older females aged 70 to 79 yr. The leading four high-risk HPV genotypes were HPV-16, HPV-52, HPV-58, and HPV-18 in descending order. In conclusion, this study provides the most representative prevalence and type-specific distribution of HPV among Korean women, and demonstrates that the epidemiology of HPV infection is different from that of other regions of the world.

Background The goal of this study was to evaluate the effect of peritrocal, intraperitoneal, or combined peritrocal-intraperitoneal ropivacaine on the parietal, visceral, and shoulder tip pain after laparoscopic cholecystectomy. Methods Eighty patients were randomly assigned to four groups. Group A received peritrocal and intraperitoneal saline. Group B received peritrocal saline and intraperitoneal ropivacaine. Group C received peritrocal ropivacaine and intraperitoneal saline. Group D received peritrocal and intraperitoneal ropivacaine. The parietal, visceral, and shoulder tip pain were assessed at 2, 4, 8, 12, 24, and 48 h postoperatively using a visual analog scale (VAS). The frequency of the patient pushing the button of the PCA and fentanyl use were also recorded. Results In visceral pain, significantly lower VAS scores were observed in Group B from 2 to 4 h and in Group D from 2 to 8 h. In parietal pain, significantly lower VAS scores were observed in Group C from 4 to 24 h and in Group D from 2 to 12 h. In shoulder tip pain, significantly lower VAS scores were observed in Group B from 4 to 48 h and in Group D from 2 to 12 h. The fentanyl use and the frequency to push the button of the PCA were the highest in Group A and the lowest in Group D at every time point. Conclusions We conclude that peritrocal infiltration of ropivacaine significantly decreases parietal pain and intraperitoneal instillation of ropivacaine significantly decreases the visceral and shoulder tip pain. Their effects are additive with respect to the total pain.

STUDY DESIGN This case report shows primary natural killer (NK)/T-cell lymphoma originating in the spine as the first case of successful treatment with autologous stem cell transplantation, along with case presentation and literature review. OBJECTIVE For the proper treatment of this spinal tumor, the pathologic confirmation includes immunophenotypic profiling, the understanding of tumor characteristics, and the consideration of spinal stability are necessary. SUMMARY OF BACKGROUND DATA NK/T-cell lymphomas are rare, aggressive neoplastic disorders with a distinctive clinical pathologic profile and an unfavorable clinical prognosis. The extranodal nasal-type NK/T-cell lymphomas, which are characterized by an extranodal presentation and an aggressive clinical course, are prevalent in Asia and Central and South America. METHODS A 49-year-old woman presented with thoracic back pain that developed 3 months before she was admitted to Chung-Ang University. The radiological image showed a 6 × 4 × 5-cm mass lesion within the T6-T7 vertebral body. The histopathology was consistent with the finding of NK/T-cell lymphoma. Treatment with chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) in combination with radiotherapy (total dose, 30 Gy) was done, and salvage therapy with autologous stem cell transplantation was performed. RESULTS Two-year follow-up magnetic resonance image showed shrinking remnant mass without spinal deformation and/or instability. Rebiopsy for remnant mass, nasal area study, and positron emission tomographic scan were performed to determine the tumor recurrence. There was no evidence of recurrence at the 2-year follow-up evaluations. CONCLUSION Some primary NK/T-cell lymphomas that originate at sites other than the nasal cavity/nasopharynx do not present with typical clinical features and symptoms. A primary NK/T-cell lymphoma of the spine should be considered in the differential diagnosis of primary bone tumors. We report the first case of successful treatment with chemoradiotherapy and autologous stem cell transplantation in a patient with a primary spinal NK/T-cell lymphoma.

Background Gemcitabine has been recognized as a standard chemotherapy in advanced pancreas cancer (APC). We conducted a phase II study of a triple combination regimen (GPT) consisting of gemcitabine (G), cisplatin (P) and erlotinib (T) in patients with APC. Patients and methods Chemotherapy-naive patients with locally advanced or metastatic, histologically confirmed adenocarcinoma of the pancreas were treated with erlotinib 100 mg daily, 1,000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin administered on days 1 and 8, respectively, every 3 weeks. The primary end point was objective response. Secondary end points included progression-free survival, overall survival and toxicity. The study was designed according to the optimal two-stage design. Results Twenty-two patients were enrolled between June 2009 and August 2010. No complete response was achieved and partial response was observed in 5 patients (26%), Stable disease in 7 (37%), and progressive disease in 7 (37%). The median time to progression was 4.0 months (95% CI: 2.9–5.1 months), and the median overall survival 6.8 months (95% CI: 3.7–9.9 months). The response rate in stage I reached the target (≥3/22, p0 = 10%) established for movement to stage II but this study was determined to close earlier than planned because of unexpected treatment-related deaths (3 patients). Conclusion The triple regimen of GPT is effective for APC. Treatment-related mortalities factored early closure of this GPT protocol. Considering effect and toxicity, this triple regimen seems to offer few benefits to the patients compared with gemcitabine-based doublets. (ClinicalTrials.gov number, NCT00922896).

Light chain deposition disease (LCDD) is a rare disorder associated with a clonal proliferation of plasma cells, which synthesize abnormal monoclonal immunoglobulin light chains. LCDD is characterized by systemic deposition of light chains in various organs, with the kidneys being most commonly affected. There have been few reports of isolated LCDD. We report a rare case of LCDD limited to a duodenal polyp. A 63-yr-old man visited our hospital for health screening without symptoms in 2009. On gastrofiberscopy, a duodenal polyp was observed. The biopsy showed diffuse infiltration by atypical plasma cells, which were positive for kappa-type light chains by immunohistochemistry. While the patient refused further management, we could find no evidence of recurrence until 2 yr after the initial diagnosis. It has been reported that isolated LCDD has relatively good prognosis compared to systemic LCDD. However, treatment for this disease has not been established yet.

Background : Nationwide external quality assessment (EQA) of the fecal occult blood test (FOBT) in Korea was first introduced in 2007-2009. The EQA results were analyzed to assess the current status of FOBT and to plan the continuation of the EQA program. Methods : The surveys included 40 hospitals in the preliminary survey conducted in 2007, 249 general hospitals in 2008, and 389 hospitals in 2009. In the surveys, the participating hospitals provided the results of the distributed materials and replies to the questionnaire on the FOBT test procedures and quality controls. Results : In the surveys conducted between 2007 and 2009, a total of 650 institutes submitted 653 test system results; 3 institutes used 2 kinds of methods. All of the institutes used immunologic methods; 107 institutes (16.5%) used quantitative equipments and 546 institutes (84.0%) used qualitative kits. Most quantitative tests yielded consistent positive or negative results; however, their cutoff and measured values differed according to the equipments used. A low-level material tested in 2007 was negative in the quantitative methods but positive in some qualitative methods because of lower detection limits. The discordance rates among quantitative tests were 3.2% in 2007, 4.4% in 2008, and 0% in 2009 and the rates among qualitative tests were 13.8% in 2008 and 2.6% in 2009. Semi-solid EQA materials showed the ability to evaluate the overall test procedures with acceptable stability. Conclusions : In the first Korean FOBT EQA, commercially available EQA materials were proven to be stable. Continuation of the EQA program and further education of laboratory personnel are needed to reduce inconsistency in results. Further, the test kit, procedures, and result reports must be standardized. (Korean J Lab Med 2010;30:726-33)

BACKGROUND Accurate measurement of blood glucose concentrations is essential for defining diabetes, and the minimization of ex vivo glycolysis has been recommended. Recent guidelines advocate two kinds of methods for sample collection and processing: either the sodium fluoride (NaF) method or immediate refrigeration using a serum separation tube (SST). We investigated the difference between the two methods in measuring subsequent glucose concentrations using blood specimens from participants recruited for the fourth Korean National Health and Nutrition Examination Survey. METHODS Paired venous blood samples were collected in an SST and a NaF tube from 1,103 men and women. SST serum was separated within 30 min, including standing for 15 min, and then refrigerated. The NaF samples were refrigerated, but not separated until immediately before analysis. We compared the blood glucose concentrations between the SST (SST glucose) and NaF (NaF glucose) methods. RESULTS The mean SST glucose was significantly higher than NaF glucose (99.0 mg/dL vs 96.5 mg/dL, P

This case study reports a rare fibrinogen variant, gamma Met310Thr mutation, for the first time in Korea. The case shows a point mutation from T to C in the 1,007th nucleotide of the FGG gene. This report describes a variant fibrinogen, hereinafter called "fibrinogen Yecheon", using the name after the town where the patient was living at the time of diagnosis. Fibrinogen Yecheon has a de novo heterozygous point mutation of FGG resulting in gamma Met310Thr and subsequent extra N-glycosylation at gamma Asn308. Extra N-glycosylated fibrinogen is considered a main inhibitor of normal fibrinogen activity.

Hemiparetic stroke is a common motor network disorder that affects a wide range of functional movements due to cortical and subcortical network lesions in stroke patients. Conventional magnetic resonance imaging (MRI) has been used to examine structural brain damage, but the integrity and connectivity of the whole brain are poorly understood. Hence, advanced neuroimaging with diffusion tensor imaging (DTI) has been developed to better localize fiber architecture and connectivity in the motor network or pathways that are responsible for motor impairments in hemiparetic stroke. To ascertain motor network connectivity between the involved and non-involved hemispheres in stroke patients, we analyzed the DTI data from all right hemiparetic stroke patients using fractional anisotropy (FA) and network parameters, including node degree and edge betweenness centrality (EBC). The FA values were substantially lower in the left hemisphere than the right hemisphere. Similarly, the node degree and EBC were significantly lower in the left hemisphere than the right hemisphere. The present brain network analysis may provide a useful neuropathway marker for accurate diagnosis and therapeutic intervention.