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Find video protocols related to scientific articles indexed in Pubmed.
Selection of aptamers specific for glycated hemoglobin and total hemoglobin using on-chip SELEX.
Lab Chip
PUBLISHED: 11-20-2014
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Blood glycated hemoglobin (HbA1c) levels reflecting average glucose concentrations over the past three months are fundamental for the diagnosis, monitoring, and risk assessment of diabetes. It has been hypothesized that aptamers, which are single-stranded DNAs or RNAs that demonstrate high affinity to a large variety of molecules ranging from small drugs, metabolites, or proteins, could be used for the measurement of HbA1c. Aptamers are selected through an in vitro process called systematic evolution of ligands by exponential enrichment (SELEX), and they can be chemically synthesized with high reproducibility at relatively low costs. This study therefore aimed to select HbA1c- and hemoglobin (Hb)-specific single-stranded DNA aptamers using an on-chip SELEX protocol. A microfluidic SELEX chip was developed to continuously and automatically carry out multiple rounds of SELEX to screen specific aptamers for HbA1c and Hb. HbA1c and Hb were first coated onto magnetic beads. Following several rounds of selection and enrichment with a randomized 40-mer DNA library, specific oligonucleotides were selected. The binding specificity and affinity were assessed by competitive and binding assays. Using the developed microfluidic system, the incubation and partitioning times were greatly decreased, and the entire process was shortened dramatically. Both HbA1c- and Hb-specific aptamers selected by the microfluidic system showed high specificity and affinity (dissociation constant, Kd = 7.6 ± 3.0 nM and 7.3 ± 2.2 nM for HbA1c and Hb, respectively). With further refinements in the assay, these aptamers may replace the conventional antibodies for in vitro diagnostics applications in the near future.
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Application of strong transverse magneto-optical Kerr effect on high sensitive surface plasmon grating sensors.
Opt Express
PUBLISHED: 10-17-2014
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A high sensitive sensor is demonstrated by exploiting strong transverse magneto-optical Kerr effect on a ferromagnetic surface plasmon grating. The surface plasmon grating, made of a hybridized Au/Fe/Au layer, exhibits a very dispersive Kerr parameter variation near the surface plasmon polariton (SPP) wavelength via coherent scattering of the SPP on the grating structure. Interrogating this Kerr parameter can be utilized for detecting chemical or biological objects in a fluid medium. The experiment results show the minimal detectable mass concentration of sodium chloride in a saline solution is 4.27 × 10-3 %, corresponding to a refractive index change of 7.60 × 10-6 RIU. For an avidin-biotin interaction experiment, the sensitivity of avidin detection in PBS solution is 1.97 nM, which is limited by the index fluctuation of flowing media during measurement.
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Synergistic effects of a calcium phosphate/fibronectin coating on the adhesion of periodontal ligament stem cells onto decellularized dental root surfaces.
Cell Transplant
PUBLISHED: 10-08-2014
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This study aimed to enhance the attachment of periodontal ligament stem cells (PDLSCs) onto decellularized dental root surface using surface coating with fibronectin and/or calcium phosphate (CaP), and to evaluate the activity of PDLSCs attached to a coated dental root surface following tooth replantation. PDLSCs were isolated from five dogs, and the other dental roots were used as a scaffold for carrying PDLSCs, and then assigned to one of four groups according to whether their surface was coated with CaP, fibronectin, or CaP/fibronectin, or left uncoated (control). Fibronectin increased the adhesion of PDLSCs onto dental root surfaces compared to both the control and CaP-coated groups, and simultaneous surface coating with CaP and fibronectin significantly accelerated and increased PDLSC adhesion compared to the fibronectin-only group. On in vivo tooth replantation, functionally oriented periodontal new attachment was observed on the CaP/fibronectin-coated dental roots to which autologous PDLSCs had adhered, while in the control condition dental root replantation was associated only with root resorption and ankylosis along the entire root length. CaP and fibronectin synergistically enhanced the attachment of PDLSCs onto dental root surfaces, and autologous PDLSCs could produce de novo periodontal new attachment in an experimental in vivo model.
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Rapid determination of cell mass and density using digitally controlled electric field in a microfluidic chip.
Lab Chip
PUBLISHED: 09-26-2014
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The density of a single cell is a fundamental property of cells. Cells in the same cycle phase have similar volume, but the differences in their mass and density could elucidate each cell's physiological state. Here we report a novel technique to rapidly measure the density and mass of a single cell using an optically induced electrokinetics (OEK) microfluidic platform. Presently, single cellular mass and density measurement devices require a complicated fabrication process and their output is not scalable, i.e., it is extremely difficult to measure the mass and density of a large quantity of cells rapidly. The technique reported here operates on a principle combining sedimentation theory, computer vision, and microparticle manipulation techniques in an OEK microfluidic platform. We will show in this paper that this technique enables the measurement of single-cell volume, density, and mass rapidly and accurately in a repeatable manner. The technique is also scalable - it allows simultaneous measurement of volume, density, and mass of multiple cells. Essentially, a simple time-controlled projected light pattern is used to illuminate the selected area on the OEK microfluidic chip that contains cells to lift the cells to a particular height above the chip's surface. Then, the cells are allowed to "free fall" to the chip's surface, with competing buoyancy, gravitational, and fluidic drag forces acting on the cells. By using a computer vision algorithm to accurately track the motion of the cells and then relate the cells' motion trajectory to sedimentation theory, the volume, mass, and density of each cell can be rapidly determined. A theoretical model of micro-sized spheres settling towards an infinite plane in a microfluidic environment is first derived and validated experimentally using standard micropolystyrene beads to demonstrate the viability and accuracy of this new technique. Next, we show that the yeast cell volume, mass, and density could be rapidly determined using this technology, with results comparable to those using the existing method suspended microchannel resonator.
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CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis.
Liver Int.
PUBLISHED: 08-28-2014
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Accurate prognostication of acute-on-chronic liver failure (ACLF) is essential for therapeutic decisions. Our aim was to validate a novel scoring system for predicting mortality, the chronic liver failure-sequential organ failure assessment (CLIF-SOFA), in a population of Asian patients with ACLF.
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Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.
Antimicrob. Agents Chemother.
PUBLISHED: 08-25-2014
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The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.
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Does 18F-FDG positron emission tomography-computed tomography have a role in initial staging of hepatocellular carcinoma?
PLoS ONE
PUBLISHED: 08-25-2014
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The utility of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of (18)F-FDG PET/CT in initial staging of HCC.
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An on-chip Cell-SELEX process for automatic selection of high-affinity aptamers specific to different histologically classified ovarian cancer cells.
Lab Chip
PUBLISHED: 08-22-2014
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Ovarian cancer (OvCa) is the second most common type of gynecological cancer. More seriously, the prognosis for survival is relatively poor if an early OvCa diagnosis is not achieved. However, it is extremely challenging to diagnose very early stage OvCa, when treatments are the most effective, because of the lack of specific and sensitive biomarkers. Therefore, in order to achieve early detection of OvCa, screening and identifying biomarkers with high specificity and affinity are greatly needed. In this study, an integrated microfluidic system capable of performing cell-based systematic evolution of ligands by an exponential enrichment (Cell-SELEX) process was developed for automatic, high-throughput screening of multiple cell lines to competitively select aptamer-based biomarkers for OvCa. This on-chip Cell-SELEX process only required five rounds of aptamer selection, which is much faster than using a conventional SELEX process (22 rounds). Using this on-chip process, 13 aptamers specific to OvCa cells were successfully screened and three of them showed high affinity towards target cells with dissociation constants of 1.8 nM, 8.3 nM, and 1.3 nM. Analysis of stained fluorescence images and competitive testing against multiple cancer cell lines (cervical cancer, breast cancer, lung cancer, and liver cancer) were performed to verify the specificity of these selected aptamers. The results demonstrated that this developed system could perform the on-chip Cell-SELEX selection successfully and could be applied for personalized aptamer screening or targeted therapy monitoring in the near future.
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A microfluidic system integrated with buried optical fibers for detection of Phalaenopsis orchid pathogens.
Biosens Bioelectron
PUBLISHED: 08-17-2014
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Orchids of the genus Phalaenopsis are some of the most economically important plants in Taiwan. Fast, accurate, and on-site detection of pathogens in these orchids is therefore of critical importance in order to prevent or suppress costly disease outbreaks. Traditional pathogen detection methods are time-consuming, require well-equipped laboratories with highly trained personnel, and cannot be conducted in situ. In this study, a microfluidic system integrated with buried optical fibers was developed to detect viral pathogens of Phalaenopsis spp. Briefly, virus-specific ribonucleic acid (RNA) purification was achieved by a pre-treatment incubation with magnetic beads, and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) was used subsequently to amplify the viral RNA. Positive RT-LAMP reactions resulted in the precipitation of magnesium pyrophosphate, which caused a change in turbidity that could be seen by the naked eye. A buried optical fiber-based detection module and a micro-stirring device were then integrated into the microfluidic chip to detect the RT-LAMP reaction product directly on the chip itself by measuring the change in the optical signals caused by the turbidity change associated with a positive amplification. The limit of detection for this system was found to be 25 fg, which is of similar sensitivity to existing, more laborious methods. Therefore, by using the integrated microfluidic system, a sensitive, rapid, accurate, and automatic diagnosis of viral pathogens in Phalaenopsis spp. orchids could be achieved within only 65 min.
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Are Delayed Operations Effective for Patients With Rotator Cuff Tears and Concomitant Stiffness? An Analysis of Immediate Versus Delayed Surgery on Outcomes.
Arthroscopy
PUBLISHED: 08-09-2014
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The purpose of this study was to compare the clinical outcomes of immediate rotator cuff repair with capsular release and those of rotator cuff repair after the stiffness was treated with rehabilitative therapy.
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Electromagnetic thermotherapy for deep organ ablation by using a needle array under a synchronized-coil system.
IEEE Trans Biomed Eng
PUBLISHED: 07-18-2014
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Thermal ablation by using electromagnetic thermotherapy (EMT) has been a promising cancer modality in recent years. It has relatively few side effects and has therefore been extensively investigated for a variety of medical applications in internal medicine and surgery. The EMT system applies a high-frequency alternating electromagnetic field to heat up the needles which are inserted into the target tumor to cause tumor ablation. In this study, a new synchronized-coil EMT system was demonstrated, which was equipped with two synchronized coils and magnetic field generators to provide a long-range, penetrated electromagnetic field to effectively heat up the needles. The heating effect of the needles at the center of the two coils was first explored. The newly designed two-section needle array combined with the synchronized-coil EMT system was thus demonstrated in the in vitro and in vivo animal experiments. Experimental data showed that the developed system is promising for minimally invasive surgery since it might provide superior performance for thermotherapy in cancer treatment.
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Identification of the rare compound heterozygous variants in the NEB gene in a Korean family with intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness.
J. Hum. Genet.
PUBLISHED: 07-17-2014
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We examined a Korean family with complex phenotypes characterized by intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness. Since we did not find any abnormality using several conventional genetic tests for detection of chromosomal aberrations, gene copy number variations and mitochondrial gene mutations, we aimed to identify disease-causing genetic alteration(s) in this family. We conducted whole-exome sequencing (WES) in this family. After filtering the WES data, we compared five exome sequences of two affected siblings, one unaffected sibling and the unaffected parents, and we determined the allele frequency of the identified variants in an Asian population. Finally, we selected one candidate variant pair which is unique in the patients and corresponds to an autosomal recessive genetic model. The two affected siblings had the same compound heterozygous variation in the NEB gene encoding nebulin, which was composed of two different missense variants: c.2603T>C (p.L868P) in exon 27 and c.21340C>T (p.R7114W) in exon 143. We confirmed these variations by Sanger sequencing. On the basis of the fundamental role of nebulin in the brain and skeletal muscles, we concluded that this compound heterozygous NEB variation may be a sound candidate for the disease-causing mutation in this family. Since the patients are characterized by generalized muscle weakness together with neurodevelopmental phenotypes, it is suggested that NEB mutations could manifest more diverse phenotypes than those previously described.Journal of Human Genetics advance online publication, 9 October 2014; doi:10.1038/jhg.2014.87.
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Rapid isolation and diagnosis of live bacteria from human joint fluids by using an integrated microfluidic system.
Lab Chip
PUBLISHED: 07-10-2014
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Arthroplasty is a general approach for improving the life quality for patients with degenerative or injured joints. However, post-surgery complications including periprosthetic joint infection (PJI) poses a serious drawback to the procedure. Several methods are available for diagnosing PJI, but they are time-consuming or have poor sensitivity and specificity. Alternatively, reverse-transcription PCR can detect live bacteria and reduce false-positive results but cannot avoid the cumbersome RNA handling and human contamination issues. In response, an integrated microfluidic system capable of detecting live bacteria from clinical PJI samples within 55 minutes is developed in this study. This system employs an ethidium monoazide (EMA)-based assay and a PCR with universal bacterial primers and probes to isolate and detect only the live bacteria that commonly cause PJI. The experimental results indicated that the developed system can detect bacteria in human joint fluids with a detection limit of 10(4) colony formation unit mL(-1). Furthermore, nine clinical samples were analyzed using the microfluidic system. The results obtained from the microfluidic system were negative for all culture-negative cases, indicating that the proposed system can indeed reduce false-positive results. In addition, experimental results showed that the EMA sample pre-treatment process was crucial for successful detection of live bacteria. The culture-positive cases were diagnosed as positive by the proposed system only when the clinical samples were treated with EMA immediately after being sampled from patients. Based on these promising results, the developed microfluidic system can be a useful tool to detect PJI and potentially be applied in other clinical situations.
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Optically induced dielectropheresis sorting with automated medium exchange in an integrated optofluidic device resulting in higher cell viability.
Lab Chip
PUBLISHED: 06-09-2014
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We demonstrated the integration of a microfluidic device with an optically induced dielectrophoresis (ODEP) device such that the critical medium replacement process was performed automatically and the cells could be subsequently manipulated by using digitally projected optical images. ODEP has been demonstrated to generate sufficient forces for manipulating particles/cells by projecting a light pattern onto photoconductive materials which creates virtual electrodes. The production of the ODEP force usually requires a medium that has a suitable electrical conductivity and an appropriate dielectric constant. Therefore, a 0.2 M sucrose solution is commonly used. However, this requires a complicated medium replacement process before one is able to manipulate cells. Furthermore, the 0.2 M sucrose solution is not suitable for the long-term viability of cells. In comparison to conventional manual processes, our automated medium replacement process only took 25 minutes. Experimental data showed that there was up to a 96.2% recovery rate for the manipulated cells. More importantly, the survival rate of the cells was greatly enhanced due to this faster automated process. This newly developed microfluidic chip provided a promising platform for the rapid replacement of the cell medium and this was also the first time that an ODEP device was integrated with other active flow control components in a microfluidic device. By improving cell viability after cell manipulation, this design may contribute to the practical integration of ODEP modules into other lab-on-a-chip devices and biomedical applications in the future.
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Carbon nanotube-based hot-film and temperature sensor assembled by optically-induced dielectrophoresis.
IET Nanobiotechnol
PUBLISHED: 06-04-2014
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The development of carbon nanotube (CNT)-based sensors remains an active area of research. Towards this end, a new method for manipulating CNTs, assembling CNT networks and fabricating CNT-based nanosensors was demonstrated in this study. CNTs were collected and concentrated by optically-induced dielectrophoresis (ODEP) forces and aligned between a pair of electrodes. This assembly was then used directly as a temperature sensor and a hot-film anemometer, which detects changes in windspeed. By offering efficient CNT collection and ready-to-use sensor fabrication, this ODEP-based approach presents a promising method for the development of CNT-based sensing applications and massively parallel assembly of CNT-lines. The developed CNT-based nanosensors may be used to measure the temperature and the flow velocity of bio-samples in the near future.
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The Korean Medication Algorithm for Depressive Disorder: second revision.
J Affect Disord
PUBLISHED: 05-19-2014
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This study constitutes a revision of the guidelines for the treatment of major depressive disorder (MDD) issued by the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) 2006. In incorporates changes in the experts? consensus that occurred between 2006 and 2012 as well as information regarding newly developed and recently published clinical trials.
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Influenza A virus-specific aptamers screened by using an integrated microfluidic system.
Lab Chip
PUBLISHED: 05-12-2014
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The influenza A virus is a notorious pathogen that causes high morbidity, high mortality, and even severe global pandemics. Early and rapid diagnosis of the virus is therefore crucial in preventing and controlling any influenza outbreaks. Recently, novel nucleic acid-based affinity reagents called aptamers have emerged as promising candidates for diagnostic assays as they offer several advantages over antibodies, including in vitro selection, chemical synthesis, thermal stability and relatively low costs. Aptamers with high sensitivity and specificity are generated via Systematic Evolution of Ligands by Exponential Enrichment (SELEX), a process that is currently time-consuming, as well as labor- and resource-intensive. In this study, an integrated microfluidic system was developed and was successfully applied to screen a specific aptamer for the influenza A/H1N1 (InfA/H1N1) virus in an automated and highly efficient manner. The selected aptamer was implemented in a magnetic-bead assay, which demonstrated specific and sensitive detection of the InfA/H1N1 virus, even in biological samples such as throat swabs. Consequently, this specific aptamer presents a promising affinity reagent for clinical diagnosis of InfA/H1N1. This is the first demonstration of screening influenza virus-specific aptamers using the microfluidic SELEX technology, which may be expanded for the rapid screening of aptamers against other pathogens for future biomedical applications.
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Rapid and amplification-free detection of fish pathogens by utilizing a molecular beacon-based microfluidic system.
Biosens Bioelectron
PUBLISHED: 05-07-2014
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Nervous necrosis virus (NNV) and iridovirus are highly infectious pathogens that can cause lethal diseases in various species of fish. These infectious diseases have no effective treatments and the mortality rate is over 80%, which could cause dramatic economic losses in the aquaculture industry. Conventional diagnostic methods of NNV or iridovirus infected fishes, such as virus culture, enzyme-linked immunosorbent assays and nucleic acid assays usually require time-consuming and complex procedures performed by specialized technicians with delicate laboratory facilities. Rapid, simple, accurate and on-site detection of NNV and iridovirus infections would enable timely preventive measures such as immediate sacrifice of infected fishes, and is therefore critically needed for the aquaculture industry. In this study, a microfluidic-based assay that employ magnetic beads conjugated with viral deoxyribonucleic acid (DNA) capturing probes and fluorescent DNA molecular beacons were developed to rapidly detect NNV and iridovirus. Importantly, this new assay was realized in an integrated microfluidic system with a custom-made control system. With this approach, direct and automated NNV and iridovirus detection from infected fishes can be achieved in less than 30 min. Therefore, this molecular-beacon based microfluidic system presents a potentially promising tool for rapid diagnosis of fish pathogens in the field in the future.
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Association between TLR1 polymorphisms and alopecia areata.
Autoimmunity
PUBLISHED: 04-29-2014
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Toll-like receptors (TLRs) may contribute to the process of autoimmune attacks on hair follicles. To investigate whether the TLR1 gene polymorphisms are associated with the development and clinical features of alopecia areata (AA), a case-control comparison of two single nucleotide polymorphisms (SNPs) (rs4833095, Asn248Ser and rs5743557, -414C?>?T) of TLR1 were studied in 239 AA patients and 248 controls. Using multiple logistic regression model, odds ratios, 95% confidence intervals and corresponding p values were estimated. Clinical features were analyzed based on the age of onset, family history, type of AA, nail involvement and body hair involvement. The missense SNP rs4833095 was significantly associated with the development of AA (codominant2, p?=?0.002; recessive, p?=?0.001; log-additive, p?=?0.0071; and allele frequency, p?=?0.0066). The promoter SNP rs5743557 was weakly associated with the development of AA (codominant2, p?=?0.019; recessive, p?=?0.032; log-additive, p?=?0.020; and allele frequency, p?=?0.03). In the clinical features, rs4833095 was only weakly associated with age of onset between 15 and 50 years (codominant2, p?=?0.043 and recessive, p?=?0.022). The results suggest that rs4833095 of TLR1 may be associated with the susceptibility for AA in the Korean population.
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HOXA9 inhibits migration of lung cancer cells and its hypermethylation is associated with recurrence in non-small cell lung cancer.
Mol. Carcinog.
PUBLISHED: 04-07-2014
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This study was aimed at understanding the clinicopathological significance of HOXA9 hypermethylation in non-small cell lung cancer (NSCLC). HOXA9 hypermethylation was characterized in six lung cancer cell lines, and its clinicopathological significance was analyzed using methylation-specific PCR in 271 formalin-fixed paraffin-embedded tissues and 27 fresh-frozen tumor and matched normal tissues from 298 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA9 was highly methylated in six lung cancer cell lines, but not in normal bronchial epithelial cells. The loss of expression was restored by treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC). Transient transfection of HOXA9 into H23 lung cancer cells resulted in the inhibition of cell migration but not proliferation. Conversely, sequence-specific siRNA-mediated knockdown of HOXA9 enhanced cell migration. The mRNA levels of HOXA9 in 27 fresh-frozen tumor tissues were significantly lower than in matched normal tissues (P?
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Phenotype difference between familial and sporadic ankylosing spondylitis in Korean patients.
J. Korean Med. Sci.
PUBLISHED: 04-01-2014
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Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6 ± 22.2 vs 35.4 ± 34.4, P=0.029) and C-reactive protein (CRP) (1.24 ± 1.7 vs 2.43 ± 3.3, P=0.003) at diagnosis, body mass index (21.9 ± 2.7 vs 23.7 ± 3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.
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Effects of Mineral Trioxide Aggregate Mixed with Hydration Accelerators on Osteoblastic Differentiation.
J Endod
PUBLISHED: 03-25-2014
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Despite good physical and biological properties, mineral trioxide aggregate (MTA) has a long setting time. A hydration accelerator could decrease the setting time of MTA. This study assessed the biocompatibility of MTA mixed with hydration accelerators (calcium chloride and low-dose citric acid) and investigated the effect of these materials on osteoblast differentiation.
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Blood genomic profiling in extracranial- and intracranial atherosclerosis in ischemic stroke patients.
Thromb. Res.
PUBLISHED: 03-24-2014
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Extracranial- and intracranial atherosclerosis (ECAS and ICAS) have been suggested to have different pathogeneses. Blood genomic profiling may identify their unique molecular signatures.
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Cytotoxicity and physical properties of tricalcium silicate-based endodontic materials.
Restor Dent Endod
PUBLISHED: 03-21-2014
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The aim of this study was to evaluate the cytotoxicity, setting time and compressive strength of MTA and two novel tricalcium silicate-based endodontic materials, Bioaggregate (BA) and Biodentine (BD).
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Extracellular-controlled breast cancer cell formation and growth using non-UV patterned hydrogels via optically-induced electrokinetics.
Lab Chip
PUBLISHED: 02-18-2014
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The culturing of cancer cells on micropatterned substrates can provide insight into the factors of the extracellular environment that enable the control of cell growth. We report here a novel non-UV-based technique to quickly micropattern a poly-(ethylene) glycol diacrylate (PEGDA)-based hydrogel on top of modified glass substrates, which were then used to control the growth patterns of breast cancer cells. Previously, the fabrication of micropatterned substrates required relatively complicated steps, which made it impractical for researchers to rapidly and systematically investigate the effects of different cell growth patterns. The technique presented herein operates on the principle of optically-induced electrokinetics (OEKs) and uses computer-generated projection light patterns to dynamically pattern the hydrogel on a hydrogenated amorphous silicon (a-Si:H) thin-film, atop an indium tin oxide (ITO) glass substrate. This technique allows us to pattern lines, circles, pentagons, and more complex shapes in the hydrogel with line widths below 3 ?m and thicknesses of up to 6 ?m within 8 s by simply controlling the projected illumination pattern and applying an appropriate AC voltage between the two ITO glass substrates. After separating the glass substrates to expose the patterned hydrogel, we experimentally demonstrate that MCF-7 breast cancer cells will adhere to the bare a-Si:H surface, but not to the hydrogel patterned in various geometric shapes and sizes. Theoretical analysis and finite-element model simulations reveal that the dominant OEK forces in our technique are the dielectrophoresis (DEP) force and the electro-osmosis force, which enhance the photo-initiated cross-linking reaction in the hydrogel. Our preliminary cultures of breast cancer cells demonstrate that this reported technique could be applied to effectively confine the growth of cancer cells on a-Si:H surfaces and affect individual cell geometry during their growth.
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Reconstruction of vascular structure with multicellular components using cell transfer printing methods.
Adv Healthc Mater
PUBLISHED: 02-12-2014
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Natural vessel has three types of concentric cell layers that perform their specific functions. Here, the fabrication of vascular structure is reported by transfer printing of three different cell layers using thermosensitive hydrogels. Tetronic-tyramine and RGD peptide are co-crosslinked to prepare cell adhesive and thermosensitive hydrogels. The hydrogel increases its diameter by 1.26 times when the temperature reduces from 37 °C to 4 °C. At optimized seeding density, three types of cells form monolayers on the hydrogel, which is then transferred to the target surface within 3 min. Three monolayers are simultaneously transferred on one substrate with controlled shape and arrangement. The same approach is applied onto nanofiber scaffolds that are cultured for more than 5 d. Every type of monolayer shows proliferation and migration on nanofiber scaffolds, and the formation of robust cell-cell contact is revealed by CD31 staining in endothelial cell layer. A vascular structure with multicellular components is fabricated by transfer of three monolayers on nanofibers that are manually rolled with the diameter and length of the tube being approximately 3 mm and 12 mm, respectively. Collectively, it is concluded that the tissue transfer printing is a useful tool for constructing a vascular structure and mimicking natural structure of different types of tissues.
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One-year rehospitalization rates of patients with first-episode bipolar mania receiving lithium or valproate and adjunctive atypical antipsychotics.
Psychiatry Clin. Neurosci.
PUBLISHED: 02-10-2014
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We compared the 1-year rehospitalization rates of first-episode bipolar manic patients who were discharged while being treated with lithium or valproate in combination with an atypical antipsychotic.
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Thoracic coupled motions of korean men in good health in their 20s.
J Phys Ther Sci
PUBLISHED: 02-06-2014
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[Purpose] The purpose of this study was to investigate thoracic coupled motions of 20 Korean young individuals. [Methods] Thoracic motion of twenty healthy male college students aged 23.2±3.1 was examined. The coupled motions of the thoracic regions T1-4, T4-8, T8-12 were measured using a three dimensional motion capture system. [Results] Coupled axial rotation in the same direction as lateral bending was observed in T1-T4 and T4-T8 in the neutral, flexed, and extended postures of the thoracic spine. In T8-T12, coupled axial rotation in the same direction as lateral bending were observed in the neutral and flexed postures, while coupled axial rotation in the opposite direction was observed in an extended posture. [Conclusion] The patterns of coupled motions in the thoracic spine demonstrated some variability between postures and regions in vivo. However, coupled motions in the same direction were predominantly lateral flexion or axial rotation in the three postures.
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Location and conformation of amyloid ?(25-35) peptide and its sequence-shuffled peptides within membranes: implications for aggregation and toxicity in PC12 Cells.
ChemMedChem
PUBLISHED: 01-27-2014
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Extracellular deposits of amyloid ? (A?) aggregates in the brain is the hallmark of Alzheimer's disease. We present the configurations (location and conformation) and the interfacial folding and membrane insertion mechanisms of A? fragments, wild-type A?(25-35), A?(35-25), and a sequence-shuffled peptide [A?(25-35)-shuffled] from A?(25-35) within membranes by replica-exchange molecular dynamics simulations. Although these peptides have the same amino acid composition, simulations show they have distinct locations and conformations within membranes. Moreover, our in vitro experiments show that these peptides have distinct neurotoxicities. We rationalize the distinct neurotoxicities of these peptides in terms of their simulated locations and conformations in membranes. This work provides another view that complements the general hydrophobicity-toxicity views, to better explain the neurotoxicity of A? peptides.
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Effects of 3 endodontic bioactive cements on osteogenic differentiation in mesenchymal stem cells.
J Endod
PUBLISHED: 01-21-2014
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Because a root-end filling material comes into contact with the surrounding cells or tissues, understanding the cell-material interfacial activity is important. Thus, the purpose of this study was to assess the biocompatibility of 3 endodontic bioactive cements (MTA [Dentsply, Tulsa, OK], Bioaggregate [BA; Innovative Bioceramix, Vancouver, BC, Canada], and Biodentine [BD; Septodont, St Maur des Fosses, France]) and to investigate the effect of cements on the differentiation of mesenchymal stem cells.
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Korean medication algorithm for depressive disorder: comparisons with other treatment guidelines.
Psychiatry Investig
PUBLISHED: 01-21-2014
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We aimed to compare the recommendations of the Korean Medication Algorithm Project for Depressive Disorder 2012 (KMAP-DD 2012) with other recently published treatment guidelines for depressive disorder. We reviewed a total of five recently published global treatment guidelines and compared each treatment recommendation of the KMAP-DD 2012 with those in other guidelines. For initial treatment recommendations, there were no significant major differences across guidelines. However, in the case of nonresponse or incomplete response to initial treatment, the second recommended treatment step varied across guidelines. For maintenance therapy, medication dose and duration differed among treatment guidelines. Further, there were several discrepancies in the recommendations for each subtype of depressive disorder across guidelines. For treatment in special populations, there were no significant differences in overall recommendations. This comparison identifies that, by and large, the treatment recommendations of the KMAP-DD 2012 are similar to those of other treatment guidelines and reflect current changes in prescription pattern for depression based on accumulated research data. Further studies will be needed to address several issues identified in our review.
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Prior exposure to lamivudine increases entecavir resistance risk in chronic hepatitis B Patients without detectable lamivudine resistance.
Antimicrob. Agents Chemother.
PUBLISHED: 01-06-2014
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The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1, n=142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2, n=233), and patients with LAM-R when starting ETV (group 3, n=125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR]=14.4, P<0.001) but also in group 2 (HR=5.0, P<0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR=13.0, P=0.013) as well as group 3 (HR=43.9, P<0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.
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Multi-step formation of a hemifusion diaphragm for vesicle fusion revealed by all-atom molecular dynamics simulations.
Biochim. Biophys. Acta
PUBLISHED: 01-04-2014
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Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipid clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
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Vertical blockade of the IGFR- PI3K/Akt/mTOR pathway for the treatment of hepatocellular carcinoma: the role of survivin.
Mol. Cancer
PUBLISHED: 01-03-2014
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To explore whether combining inhibitors that target the insulin-like growth factor receptor (IGFR)/PI3K/Akt/mTOR signaling pathway (vertical blockade) can improve treatment efficacy for hepatocellular carcinoma (HCC).
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A HIPAA-compliant key management scheme with revocation of authorization.
Comput Methods Programs Biomed
PUBLISHED: 01-02-2014
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Patient control over electronic protected health information (ePHI) is one of the major concerns in the Health Insurance and Accountability Act (HIPAA). In this paper, a new key management scheme is proposed to facilitate control by providing two functionalities. First, a patient can authorize more than one healthcare institute within a designated time period to access his or her ePHIs. Second, a patient can revoke authorization and add new authorized institutes at any time as necessary. In the design, it is not required to re-encrypt ePHIs for adding and revoking authorizations, and the implementation is time- and cost-efficient. Consent exception is also considered by the proposed scheme.
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Lichen Secondary Metabolites in Flavocetraria cucullata Exhibit Anti-Cancer Effects on Human Cancer Cells through the Induction of Apoptosis and Suppression of Tumorigenic Potentials.
PLoS ONE
PUBLISHED: 01-01-2014
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Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT.
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Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4+ T cells.
PLoS ONE
PUBLISHED: 01-01-2014
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To avoid excessive activation, immune signals are tightly controlled by diverse inhibitory proteins. TRIM30, a tripartite motif (TRIM)-containing protein is one of such inhibitors known to function in macrophages. To define the roles of TRIM30, we generated Trim30 knockout (Trim30-/-) mice. Trim30 deletion caused no major developmental defects in any organs, nor showed any discernable defect in the activation of macrophages. But, Trim30-/- mice showed increased CD4/CD8 ratio when aged and Trim30-/- CD4+ T cells exhibited an abnormal response upon TCR activation, in particular in the absence of a costimulatory signal. Adoptive transfer of wild-type and Trim30-/- CD4+ T cells together into lymphopenic hosts confirmed higher proliferation of the Trim30-/- CD4+ T cells in vivo. Despite the enhanced proliferation, Trim30-/- T cells showed decreased levels of NF-?B activation and IL-2 production compared to wild-type cells. These results indicate a distinct requirement for TRIM30 in modulation of NF-?B activation and cell proliferation induced by TCR stimulation.
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Rapid and label-free separation of Burkitt's lymphoma cells from red blood cells by optically-induced electrokinetics.
PLoS ONE
PUBLISHED: 01-01-2014
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Early stage detection of lymphoma cells is invaluable for providing reliable prognosis to patients. However, the purity of lymphoma cells in extracted samples from human patients' marrow is typically low. To address this issue, we report here our work on using optically-induced dielectrophoresis (ODEP) force to rapidly purify Raji cells' (a type of Burkitt's lymphoma cell) sample from red blood cells (RBCs) with a label-free process. This method utilizes dynamically moving virtual electrodes to induce negative ODEP force of varying magnitudes on the Raji cells and RBCs in an optically-induced electrokinetics (OEK) chip. Polarization models for the two types of cells that reflect their discriminate electrical properties were established. Then, the cells' differential velocities caused by a specific ODEP force field were obtained by a finite element simulation model, thereby established the theoretical basis that the two types of cells could be separated using an ODEP force field. To ensure that the ODEP force dominated the separation process, a comparison of the ODEP force with other significant electrokinetics forces was conducted using numerical results. Furthermore, the performance of the ODEP-based approach for separating Raji cells from RBCs was experimentally investigated. The results showed that these two types of cells, with different concentration ratios, could be separated rapidly using externally-applied electrical field at a driven frequency of 50 kHz at 20 Vpp. In addition, we have found that in order to facilitate ODEP-based cell separation, Raji cells' adhesion to the OEK chip's substrate should be minimized. This paper also presents our experimental results of finding the appropriate bovine serum albumin concentration in an isotonic solution to reduce cell adhesion, while maintaining suitable medium conductivity for electrokinetics-based cell separation. In short, we have demonstrated that OEK technology could be a promising tool for efficient and effective purification of Raji cells from RBCs.
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Serum insulin-like growth factor-1 predicts disease progression and survival in patients with hepatocellular carcinoma who undergo transarterial chemoembolization.
PLoS ONE
PUBLISHED: 01-01-2014
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Insulin like-growth factor-1 (IGF-1) reflects hepatic synthetic function and plays a major role in the development and progression of various cancers. In the present study, we investigated whether baseline serum IGF-1 levels predict time-to-progression (TTP) and overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). A total of 155 consecutive treatment-naive patients with HCC who had undergone TACE as initial treatment were included from a prospective cohort. Baseline serum IGF-1 levels were analyzed with regard to their associations with disease progression and survival. During a median follow-up period of 41.8 months, patients with low IGF-1 levels showed significantly shorter TTP (median, 6.0 months; 95% confidence interval [CI], 4.5-7.6) than patients with high IGF-1 levels (median, 16.5 months; 95% CI, 4.9-28.1; p?=?0.003). In the multivariate analysis, BCLC stage, serum vascular endothelial growth factorlevels, and IGF-1 levels were independent risk factors for disease progression. The hazard ratio (HR) of progression for each 10 ng/mL decrease in IGF-1 level was 1.072 (95% CI, 1.029-1.117; p?=?0.001). Furthermore, together with tumor size, stage, and treatment response, IGF-1 levels were an independent predictor of poorer survival (for each 10 ng/mL decrease in IGF-1 level; HR, 1.057; 95% CI, 1.001-1.115; p?=?0.045). In conclusion, low baseline IGF-1 levels independently correlated with shorter TTP and poorer OS in patients with HCC who underwent TACE.
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Nonalcoholic fatty liver disease is a negative risk factor for prostate cancer recurrence.
Endocr. Relat. Cancer
PUBLISHED: 01-01-2014
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Nonalcoholic fatty liver disease (NAFLD) is closely related to the metabolic syndrome, which is associated with an increased risk of various malignancies. In this study, we investigated the association between NAFLD and prostate cancer biochemical recurrence (BCR) after radical prostatectomy. Consecutive prostate cancer patients who underwent radical prostatectomy were enrolled from two hospitals in Korea and randomly assigned to the training (n=147) or validation set (n=146). The presence of NAFLD, BMI, preoperative prostate-specific antigen, and histological findings including Gleason score (GSc) were analyzed in regard to their association with BCR. NAFLD was diagnosed based on ultrasonography or unenhanced computed tomography images. BCR-free survival rates were calculated using the Kaplan-Meier method. In the training set, 32 (21.8%) patients developed BCR during a median follow-up period of 51 (inter-quartile range, 35-65) months. In the multivariate analysis, the presence of NAFLD (hazard ratio (HR), 0.36; 95% CI, 0.14-0.97; P=0.04) was an independent negative predictive factor of BCR after adjustment for pathological GSc. Applied to the validation set, the presence of NAFLD maintained its prognostic value for longer time-to-BCR (HR, 0.17; 95% CI, 0.06-0.49; P=0.001). In the subgroup analysis of patients with NAFLD, NAFLD fibrosis score was a single independent negative predictor for BCR (HR, 0.54; 95% CI, 0.30-0.98; P=0.04). Our study demonstrated that NAFLD may play a protective role against BCR after radical prostatectomy for prostate cancer. Further study is warranted to elucidate the mechanism of protective effect in patients with NAFLD.
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Dielectrophoretically-assisted electroporation using light-activated virtual microelectrodes for multiple DNA transfection.
Lab Chip
PUBLISHED: 12-09-2013
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Gene transfection is an important technology for various biological applications. The exogenous DNA is commonly delivered into cells by using a strong electrical field to form transient pores in cellular membranes. However, the high voltage required in this electroporation process may cause cell damage. In this study, a dielectrophoretically-assisted electroporation was developed by using light-activated virtual microelectrodes in a new microfluidic platform. The DNA electrotransfection used a low applied voltage and an alternating current to enable electroporation and transfection. Single or triple fluorescence-carrying plasmids were effectively transfected into various types of mammalian cells, and the fluorescent proteins were successfully expressed in live transfected cells. Moreover, the multi-triangle optical pattern that was projected onto a photoconductive layer to generate localized non-uniform virtual electric fields was found to have high transfection efficiency. The developed dielectrophoretically-assisted electroporation platform may provide a simpler system for gene transfection and could be widely applied in many biotechnological fields.
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Rapid transfer of endothelial cell sheet using a thermosensitive hydrogel and its effect on therapeutic angiogenesis.
Biomacromolecules
PUBLISHED: 11-27-2013
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In this study, thermosensitive hydrogels incorporated with multiple cell-interactive factors were developed as a substrate to form monolayer of human umbilical vein endothelial cells (HUVECs) that can be detached and transferrable to target sites as a cell-sheet in response to temperature change. The cell adhesive peptide (RGD) and growth factor (bFGF) covalently incorporated within the hydrogel significantly enhanced adhesion and proliferation of HUVECs, allowing for the formation of their confluent monolayer. Meanwhile, the precisely controllable change in the size of the hydrogels was observed by a repeated increase and decrease in temperature from 37 to 4 °C. By exploiting this unique behavior, the detachment and transfer of HUVEC sheet confluently cultured at 37 °C was rapidly induced within 10 min by expansion of the hydrogels when the temperature was decreased to 4 °C. The transferred cell sheet was highly viable and maintained robust cell-cell junction. Finally, the process of cell sheet transfer was directly applied onto an ischemic injury in the hind limb of mice. The transplanted HUVECs as a sheet retarded tissue necrosis over 14 days in comparison with that of direct injection of the same number of cells. Our results suggest that the developed multifunctional Tetronic-tyramine hydrogels could serve as an ideal substrate to modulate the formation of an endothelial cell layer that could potentially be utilized to treat peripheral arterial disease.
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HOXA11 hypermethylation is associated with progression of non-small cell lung cancer.
Oncotarget
PUBLISHED: 11-22-2013
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This study was aimed at understanding the functional significance of HOXA11 hypermethylation in non-small cell lung cancer (NSCLC). HOXA11 hypermethylation was characterized in six lung cancer cell lines, and its clinical significance was analyzed using formalin-fixed paraffin-embedded tissues from 317 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA11 was highly methylated in six lung cancer cell lines, but not in normal bronchial epithelial cells. The loss of expression was restored by treatment of the cells with a demethylating agent, 5-aza-2-deoxycytidine (5-Aza-dC). Transient transfection of HOXA11 into H23 lung cancer cells resulted in the inhibition of cell migration and proliferation. HOXA11 hypermethylation was found in 218 (69%) of 317 primary NSCLCs. HOXA11 hypermethylation was found at a higher prevalence in squamous cell carcinoma than in adenocarcinoma (74% vs. 63%, respectively). HOXA11 hypermethylation was associated with Ki-67 proliferation index (P = 0.03) and pT stage (P = 0.002), but not with patient survival. Patients with pT2 and pT3 stages were 1.85 times (95% confidence interval [CI] = 1.04-3.29; P = 0.04) and 5.47 times (95% CI = 1.18-25.50; P = 0.01), respectively, more likely to show HOXA11 hypermethylation than those with pT1 stage, after adjusting for age, sex, and histology. In conclusion, the present study suggests that HOXA11 hypermethylation may contribute to the progression of NSCLC by promoting cell proliferation or migration.
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Structural and magnetic features of oxygen inserted [Co-O/Pt]n multi-layer matrix for spin transfer torque memory applications.
J Nanosci Nanotechnol
PUBLISHED: 11-20-2013
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We describe the influence of inserted oxygen atoms on the structural and magnetic properties of a [Co/Pt]n multi-layer matrix. The correlation of magnetic properties with oxygen gas flow rate was studied as an alternative perpendicular medium in spin transfer torque magnetic random access memory applications. Experimental analysis suggests that the addition of a small amount of oxygen atoms into the [Co/Pt]n multi-layer matrix leads to a high coercivity and proper magnetization performance, together with high thermal stability. Finally, the nature of the improved perpendicular medium behaviors is also discussed.
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Fast neuromorphic sound localization for binaural hearing aids.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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We report on the neuromorphic sound localization circuit which can enhance the perceptual sensation in a hearing aid system. All elements are simple leaky integrate-and-fire neuron circuits with different parameters optimized to suppress the impacts of synaptic circuit noises. The detection range and resolution of the proposed neuromorphic circuit are 500 us and 5 us, respectively. Our results show that, the proposed technique can localize a sound pulse with extremely narrow duration (? 1 ms) resulting in real-time response.
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Efficacy of adefovir-based combination therapy for patients with Lamivudine- and entecavir-resistant chronic hepatitis B virus infection.
Antimicrob. Agents Chemother.
PUBLISHED: 10-07-2013
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Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P = 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P = 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.
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Clinical Significance of ?-Tricalcium Phosphate and Polyphosphate for Mastoid Cavity Obliteration during Middle Ear Surgery: Human and Animal Study.
Clin Exp Otorhinolaryngol
PUBLISHED: 09-04-2013
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Mastoid obliteration is used to obliterate the mastoid cavity following a mastoidectomy or to prevent the formation of a retraction pocket. This study evaluated the effectiveness of ?-tricalcium phosphate and polyphosphate (?-TPP) for mastoid obliteration in middle ear surgeries in prospective human and animal studies.
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The efficacy and safety of switching to ziprasidone from olanzapine in patients with bipolar I disorder: an 8-week, multicenter, open-label study.
Clin Drug Investig
PUBLISHED: 08-31-2013
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Switching antipsychotic medication in patients undergoing combination therapy for bipolar I disorder is a common clinical practice because of suboptimal drug efficacy or tolerability. Despite the frequency of switching, little is known about the most appropriate switching options. Ziprasidone may be a good alternative for patients with bipolar disorder experiencing a suboptimal response or intolerance to olanzapine in combination with a mood stabilizer because of its mood-stabilizing effect and minimal propensity for clinically significant body weight gain and metabolic disturbances. However, no study has evaluated the efficacy, safety, and tolerability of switching to ziprasidone from olanzapine in combination with a mood stabilizer for treatment of bipolar disorder.
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Bystander-initiated CPR in an Asian metropolitan: Does the socioeconomic status matter?
Resuscitation
PUBLISHED: 06-19-2013
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To determine the association of neighborhood socioeconomic status (SES) with bystander-initiated cardiopulmonary resuscitation (CPR) and patient outcomes of out of hospital cardiac arrests (OHCAs) in an Asian metropolitan area.
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Serum insulin-like growth factor-I level is an independent predictor of recurrence and survival in early hepatocellular carcinoma: a prospective cohort study.
Clin. Cancer Res.
PUBLISHED: 06-11-2013
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Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment.
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An integrated microfluidic device utilizing vancomycin conjugated magnetic beads and nanogold-labeled specific nucleotide probes for rapid pathogen diagnosis.
Nanomedicine
PUBLISHED: 05-30-2013
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A PCR-free assay for rapid pathogen diagnosis was implemented on an integrated microfluidic system in this study. Vancomycin-conjugated magnetic beads were used to capture multiple strains of bacteria and nucleotide probes labeled gold nanoparticles were used to specify and detect a specific strain by hybridization-induced color change. The assay was entirely automated within an integrated microfluidic device that was composed of suction-type micropumps, microvalves, microchannels, and microchambers that fabricated by microfluidic technology. Multiple strains of bacteria could be captured simultaneously by vancomycin-conjugated magnetic beads, with capturing efficiency exceeding 80%. Subsequently, sensitive and strain-specific detection against target bacteria could be achieved by using nanogold labeled specific nucleotide probes. The limit of detection of 10(2)CFU bacteria was achieved. Importantly, nucleic acid amplification was not involved in the diagnostic procedures; the entire analytic process required only 25min. The developed platform may provide a promising tool for rapid diagnosis of bacterial infections.
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Plasma total homocysteine level is associated with the pulsatility index of cerebral arteries in lacunar infarction.
Yonsei Med. J.
PUBLISHED: 05-28-2013
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The pulsatility index (PI), measured by transcranial Doppler (TCD), is a surrogate marker for distal vascular resistance in cerebral arteries, and elevated plasma total homocysteine (tHcyt) is regarded as a cause of ischemic stroke, including lacunar infarction. We investigated the relationship between the PI of cerebral arteries and plasma tHcyt in patients with lacunar infarction.
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A Case of Common Bile Duct Cancer That Completely Responded to Combination Chemotherapy of Gemcitabine and TS-1.
Gut Liver
PUBLISHED: 05-13-2013
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Common bile duct (CBD) cancer is a relatively rare malignancy that arises from the biliary epithelium and is associated with a poor prognosis. Here, we report a case of advanced metastatic CBD cancer successfully treated by chemotherapy with gemcitabine combined with S-1 (tegafur+gimeracil+oteracil). A 65-year-old male presented with pyogenic liver abscess. After antibiotic therapy and percutaneous drainage, follow-up computed tomography (CT) showed an enhanced nodule in the CBD. Biopsy was performed at the CBD via endoscopic retrograde cholangiopancreatography, which showed adenocarcinoma. Additional CT and magnetic resonance imaging showed multiple small nodules in the right hepatic lobe, which were confirmed as metastatic adenocarcinoma by sono-guided liver biopsy. The patient underwent combination chemotherapy with gemcitabine and S-1. After nine courses of chemotherapy, the hepatic lesion disappeared radiologically. Pylorus-preserving pancreaticoduodenectomy was performed, and no residual tumor was found in the resected specimen. Three weeks after the operation, the patient was discharged with no complications. Through 3 months of follow-up, no sign of recurrence was observed on CT scan. Gemcitabine combined with S-1 may be a highly effective treatment for advanced cholangiocarcinoma.
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Comparative analysis of radiologically measured size and true size of renal tumors.
Korean J Urol
PUBLISHED: 04-24-2013
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We evaluated the differences between radiologically measured size and pathologic size of renal tumors.
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Genome-wide profiling of in vivo LPS-responsive genes in splenic myeloid cells.
Mol. Cells
PUBLISHED: 04-12-2013
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Lipopolysaccharide (LPS), the major causative agent of bacterial sepsis, has been used by many laboratories in genome-wide expression profiling of the LPS response. However, these studies have predominantly used in vitro cultured macrophages (Macs), which may not accurately reflect the LPS response of these innate immune cells in vivo. To overcome this limitation and to identify inflammatory genes in vivo, we have profiled genome-wide expression patterns in non-lymphoid, splenic myeloid cells extracted directly from LPS-treated mice. Genes encoding factors known to be involved in mediating or regulating inflammatory processes, such as cytokines and chemokines, as well as many genes whose immunological functions are not well known, were strongly induced by LPS after 3 h or 8 h of treatment. Most of the highly LPS-responsive genes that we randomly selected from the microarray data were independently confirmed by quantitative RT-PCR, implying that our microarray data are quite reliable. When our in vivo data were compared to previously reported microarray data for in vitro LPS-treated Macs, a significant proportion (?20%) of the in vivo LPS-responsive genes defined in this study were specific to cells exposed to LPS in vivo, but a larger proportion of them (?60%) were influenced by LPS in both in vitro and in vivo settings. This result indicates that our in vivo LPS-responsive gene set includes not only previously identified in vitro LPS-responsive genes but also novel LPS-responsive genes. Both types of genes would be a valuable resource in the future for understanding inflammatory responses in vivo.
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Magnetic nanoparticle-based immunoassay for rapid detection of influenza infections by using an integrated microfluidic system.
Nanomedicine
PUBLISHED: 04-04-2013
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Magnetic manganese ferrite (MnFe2O4) nanoparticles with approximately 100nm in diameter were used to improve the performance of an immunoassay for detecting influenza infections. The synthesized nanoparticles were tested for long-term storage to confirm the stability of their thermal decomposition process. Then, an integrated microfluidic system was developed to perform the diagnosis process automatically, including virus purification and detection. To apply these nanoparticles for influenza diagnosis, a micromixer was optimized to reduce the dead volume within the microfluidic chip. Furthermore, the mixing index of the micromixer could achieve as high as 97% in 2seconds. The optical signals showed that this nanoparticle-based immunoassay with dynamic mixing could successfully achieve a detection limit of influenza as low as 0.007 HAU. When compared with the 4.5-?m magnetic beads, the optical signals of the MnFe2O4 nanoparticles were twice as sensitive. Furthermore, five clinical specimens were tested to verify the usability of the developed system.
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The effects of isokinetic eccentric resistance exercise for the hip joint on functional gait of stroke patients.
J Phys Ther Sci
PUBLISHED: 03-28-2013
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[Purpose] The purpose of this study was to determine the effects of resistance exercise strengthening the hip flexor and extensor muscles on functional gait of stroke patients. [Subjects and Methods] Twenty patients were randomized into two groups. Both groups performed conventional physical therapy for six weeks. The experimental group also performed isokinetic eccentric resistance exercises for the hip flexor and extensor muscles. The hip muscle strength, stair up and down time, TUG time(timed up and go test), and 10?m gait velocity were measured at the baseline, and after 3 weeks, and 6 weeks of treatment. [Results] The experimental showed significant improvements compared to the baseline in hip muscle strength, stair up and down time, TUG time and 10?m gait velocity after 3 and 6 weeks of treatment. After 3 and 6 weeks of treatment, there were gains in hip muscle strength and 10?m gait velocity. The control group showed no significant increase in hip muscle strength, stair up and down time, TUG time or 10?m gait velocity. [Conclusion] We consider that conventional physical therapy contributes to the improvement of functional gait of stroke patients. However, it is more desirable to perform isokinetic eccentric resistance exercises for hip flexor and extensor muscles combined with conventional physical therapy for the improvement of hip muscle strength, stair up and down time, TUG time and 10?m gait velocity.
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An electromagnetic thermotherapy system with a deep penetration depth for percutaneous thermal ablation.
Ann Biomed Eng
PUBLISHED: 03-25-2013
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Thermal ablation has been a promising method to remove the cancerous tissues. Electromagnetic-based thermotherapy has been extensively investigated for a variety of medical applications recently. In this study, a prototype electromagnetic thermotherapy system has been developed with a new coil design and a two-section needle. The coil can generate an alternating electromagnetic field (EMF) with a deep penetration depth to remotely heat the needle which is located up to 15 cm away, enabling percutaneous thermal ablation. Several important parameters, including the heating effects of the needle at different positions, the intensity of the EMF and the induced temperature distribution on the surrounding tissue, are first explored. An in vitro animal experiment has also been performed which shows EMF-induced ablation in a porcine liver by the needle. Furthermore, an in vivo experiment on an animal model (a New Zealand white rabbit) is also conducted in the study. Thus, the two-section needle combined with the coil-generated EMF has been demonstrated to be a promising thermotherapy system for percutaneous thermal ablation.
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Detection of viruses directly from the fresh leaves of a Phalaenopsis orchid using a microfluidic system.
Nanomedicine
PUBLISHED: 03-18-2013
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Early detection of pathogens is crucial for the effective surveillance of diseases. Many efforts have been made to explore methods which can detect these pathogens within a short period of time without requiring a tedious protocol. However, these developed methods have disadvantages such as they are relatively time-consuming or require specialized laboratory facilities. In this work, we have developed an integrated microfluidic system for rapid and automatic detection of viruses by direct analysis from fresh Phalaenopsis orchid leaves. The entire protocol, including ribonucleic acid (RNA) purification, reverse transcription loop-mediated-isothermal-amplification (RT-LAMP) and optical detection by measuring changes in turbidity was performed on a single chip. This is the first time that an integrated microfluidic system for the detection of viruses infecting the Phalaenopsis orchid has been demonstrated. The sensitivity of the developed system was also explored in this study to validate its performance.
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Partial nephrectomy without renal ischemia using an electromagnetic thermal surgery system in a porcine model.
Urology
PUBLISHED: 03-07-2013
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To test the feasibility of partial nephrectomy using needle arrays under alternating current (AC) electromagnetic field without renal artery clamping.
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A molecular dynamics study of the structural and dynamical properties of putative arsenic substituted lipid bilayers.
Int J Mol Sci
PUBLISHED: 03-01-2013
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Cell membranes are composed mainly of phospholipids which are in turn, composed of five major chemical elements: carbon, hydrogen, nitrogen, oxygen, and phosphorus. Recent studies have suggested the possibility of sustaining life if the phosphorus is substituted by arsenic. Although this issue is still controversial, it is of interest to investigate the properties of arsenated-lipid bilayers to evaluate this possibility. In this study, we simulated arsenated-lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-arsenocholine (POAC), lipid bilayers using all-atom molecular dynamics to understand basic structural and dynamical properties, in particular, the differences from analogous 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, (POPC) lipid bilayers. Our simulations showed that POAC lipid bilayers have distinct structural and dynamical properties from those of native POPC lipid bilayers. Relative to POPC lipid bilayers, POAC lipid bilayers have a more compact structure with smaller lateral areas and greater order. The compact structure of POAC lipid bilayers is due to the fact that more inter-lipid salt bridges are formed with arsenate-choline compared to the phosphate-choline of POPC lipid bilayers. These inter-lipid salt bridges bind POAC lipids together and also slow down the head group rotation and lateral diffusion of POAC lipids. Thus, it would be anticipated that POAC and POPC lipid bilayers would have different biological implications.
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The difference of lower urinary tract symptoms between sympathetic hyperactive and hypoactive men.
Int Neurourol J
PUBLISHED: 02-27-2013
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Heart rate variability (HRV) is a tool used to measure autonomic nervous function; however, there is no evidence that it can be used to define sympathetic hyperactivity in men with lower urinary tract symptoms (LUTS). We suspected that LUTS would differ between sympathetic hyperactive and hypoactive patients. Therefore, we measured HRV and divided the LUTS patients into two groups, a sympathetic hyperactive group and a sympathetic hypoactive group according to the low frequency/high frequency (LF/HF) ratio and made clinical comparisons between the groups.
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A microfluidic immunomagnetic bead-based system for the rapid detection of influenza infections: from purified virus particles to clinical specimens.
Biomed Microdevices
PUBLISHED: 02-20-2013
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Seasonal and novel influenza infections have the potential to cause worldwide pandemics. In order to properly treat infected patients and to limit its spread, a rapid, accurate and automatic influenza diagnostic tool needs to be developed. This study therefore presents a new integrated microfluidic system for the rapid detection of influenza infections. It integrated a suction-type, pneumatic-driven microfluidic control module, a magnetic bead-based fluorescent immunoassay (FIA) and an end-point optical detection module. This new system can successfully distinguish between influenza A and B using a single chip test within 15 min automatically, which is faster than existing devices. By utilizing the micromixers to thoroughly wash out the sputum-like mucus, this microfluidic system could be used for the diagnosis of clinical specimens and reduced the required sample volume to 40 ?L. Furthermore, the results of diagnostic assays from 86 patient specimens have demonstrated that this system has 84.8 % sensitivity and 75.0 % specificity. This developed system may provide a powerful platform for the fast screening of influenza infections.
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Intratympanic dexamethasone injection for refractory tinnitus: prospective placebo-controlled study.
Laryngoscope
PUBLISHED: 02-19-2013
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The purpose of this study is to investigate the effectiveness of intratympanic dexamethasone injections (ITDI) for refractory tinnitus.
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Nucleic acid amplification using microfluidic systems.
Lab Chip
PUBLISHED: 02-15-2013
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In the post-human-genome-project era, the development of molecular diagnostic techniques has advanced the frontiers of biomedical research. Nucleic-acid-based technology (NAT) plays an especially important role in molecular diagnosis. However, most research and clinical protocols still rely on the manual analysis of individual samples by skilled technicians which is a time-consuming and labor-intensive process. Recently, with advances in microfluidic designs, integrated micro total-analysis-systems have emerged to overcome the limitations of traditional detection assays. These microfluidic systems have the capability to rapidly perform experiments in parallel and with a high-throughput which allows a NAT analysis to be completed in a few hours or even a few minutes. These features have a significant beneficial influence on many aspects of traditional biological or biochemical research and this new technology is promising for improving molecular diagnosis. Thus, in the foreseeable future, microfluidic systems developed for molecular diagnosis using NAT will become an important tool in clinical diagnosis. One of the critical issues for NAT is nucleic acid amplification. In this review article, recent advances in nucleic acid amplification techniques using microfluidic systems will be reviewed. Different approaches for fast amplification of nucleic acids for molecular diagnosis will be highlighted.
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Ketoprofen inhibits expression of inflammatory mediators in human dental pulp cells.
J Endod
PUBLISHED: 02-13-2013
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Conventional root canal treatment is the treatment of choice for the irreversible pulpitis caused by bacterial infection. More recently, vital pulp therapy has been proposed as an alternative for management of inflamed dental pulp. Ketoprofen is an anti-inflammatory agent commonly used as a component of mouth rinse for oral lesions. Here, we examined the effect and mechanisms of action of ketoprofen on the expression of inflammatory mediators induced by the lipopolysaccharide (LPS) in dental pulp cells.
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High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force.
Lab Chip
PUBLISHED: 02-08-2013
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Negative selection-based circulating tumor cell (CTC) isolation is believed valuable to harvest more native, and in particular all possible CTCs without biases relevant to the properties of surface antigens on the CTCs. Under such a cell isolation strategy, however, the CTC purity is normally compromised. To address this issue, this study reports the integration of optically-induced-dielectrophoretic (ODEP) force-based cell manipulation, and a laminar flow regime in a microfluidic platform for the isolation of untreated, and highly pure CTCs after conventional negative selection-based CTC isolation. In the design, six sections of moving light-bar screens were continuously and simultaneously exerted in two parallel laminar flows to concurrently separate the cancer cells from the leukocytes based on their size difference and electric properties. The separated cell populations were further partitioned, delivered, and collected through the two flows. With this approach, the cancer cells can be isolated in a continuous, effective, and efficient manner. In this study, the operating conditions of ODEP for the manipulation of prostate cancer (PC-3) and human oral cancer (OEC-M1) cells, and leukocytes with minor cell aggregation phenomenon were first characterized. Moreover, performances of the proposed method for the isolation of cancer cells were experimentally investigated. The results showed that the presented CTC isolation scheme was able to isolate PC-3 cells or OEC-M1 cells from a leukocyte background with high recovery rate (PC-3 cells: 76-83%, OEC-M1 cells: 61-68%), and high purity (PC-3 cells: 74-82%, OEC-M1 cells: 64-66%) (set flow rate: 0.1 ?l min(-1) and sample volume: 1 ?l). The latter is beyond what is currently possible in the conventional CTC isolations. Moreover, the viability of isolated cancer cells was evaluated to be as high as 94 ± 2%, and 95 ± 3% for the PC-3, and OEC-M1 cells, respectively. Furthermore, the isolated cancer cells were also shown to preserve their proliferative capability. As a whole, this study has presented an ODEP-based microfluidic platform that is capable of isolating CTCs in a continuous, label-free, cell-friendly, and particularly highly pure manner. All these traits are found particularly meaningful for exploiting the harvested CTCs for the subsequent cell-based, or biochemical assays.
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Integrated three-dimensional system-on-chip for direct quantitative detection of mitochondrial DNA mutation in affected cells.
Biosens Bioelectron
PUBLISHED: 02-05-2013
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We report a microfluidic system for automatic mitochondrial mutation diagnostics from sample purification to quantitative analysis. The system achieved direct DNA (mtDNA) mutation quantification in affected cells using a new 3D-microfluidic system, which integrated a mtDNA extraction module and a mutation detection module. Effective direct mtDNA extraction from the cells was realized using magnetic field manipulation. The obtained mtDNAs were subject to a fully automatic processing for quantitative mutation detection using integrated micropumps, micromixer and microtemperature control modules capable of mutation sensing by restriction enzyme digestion and real-time on-chip micro-PCR. Compared with traditional methods, this microfluidic system demonstrates the advantages of faster detection, requirement of fewer amount of specimens and reagents, much compact design and lower cost as well as lower risks for human errors. Thus, such system-on-chip would encourage the future translational development of rapid pathogenic mtDNA defects detection to provide more efficient clinical diagnosis and disease management strategies.
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Biocompatibility of mineral trioxide aggregate mixed with hydration accelerators.
J Endod
PUBLISHED: 01-26-2013
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The aim of this study was to evaluate the biocompatibility of mineral trioxide aggregate mixed with selective hydration accelerators such as calcium chloride (CaCl2), citric acid (CA), and calcium lactate gluconate solution (CLG).
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.