Because of the limited geographic distribution, there have been insufficient data regarding hepatitis C virus (HCV) genotype 6 in Korea. This study aimed to investigate the clinical characteristics ...and available treatment outcomes of patients with genotype 6 HCV in Korea.
From 2004 to 2014, data were collected from Korean patients infected with genotype 6 HCV in eight hospitals.
Thirty-two patients had genotype 6 HCV. The median age was 44 years, and 6c was the most common subtype. The baseline median alanine transaminase level was 88 (21 to 1,019) IU/mL, and the HCV RNA level was 1,405,000 (96,500 to 28,844,529) IU/mL. Twenty-five patients were treated with peginterferon (PEG-IFN) and ribavirin. Three follow-up losses occurred. Additionally, 13 patients attained a sustained virologic response (SVR), seven patients relapsed, and two patients exhibited a null response. The SVR rates were 40% and 75% for the 24- and more than 48-week treatments, respectively, and five of the six patients who achieved a rapid virologic response (RVR) attained a SVR.
Korean patients infected with genotype 6 HCV are relatively young, and 6c is the most common subtype. When treated with PEG-IFN and ribavirin, the SVR rate was 52%. Similar to other genotypes, a longer duration of treatment and attainment of RVR are important for SVR.
The interaction of FK-506 with K(V)1.3, stably expressed in Chinese hamster ovary cells, was investigated with the whole cell patch-clamp technique. FK-506 inhibited K(V)1.3 in a reversible, ...concentration-dependent manner with an IC(50) of 5.6 microM. Rapamycin, another immunosuppressant, produced effects that were similar to those of FK-506 (IC(50) = 6.7 microM). Other calcineurin inhibitors (cypermethrin or calcineurin autoinhibitory peptide) alone had no effect on the amplitude or kinetics of K(V)1.3. In addition, the inhibitory action of FK-506 continued, even after the inhibition of calcineurin activity. The inhibition produced by FK-506 was voltage dependent, increasing in the voltage range for channel activation. At potentials positive to 0 mV (where maximal conductance is reached), however, no voltage-dependent inhibition was found. FK-506 exhibited a strong use-dependent inhibition of K(V)1.3. FK-506 shifted the steady-state inactivation curves of K(V)1.3 in the hyperpolarizing direction in a concentration-dependent manner. The apparent dissociation constant for FK-506 to inhibit K(V)1.3 in the inactivated state was estimated from the concentration-dependent shift in the steady-state inactivation curve and was calculated to be 0.37 microM. Moreover, the rate of recovery from inactivation of K(V)1.3 was decreased. In inside-out patches, FK-506 not only reduced the current amplitude but also accelerated the rate of inactivation during depolarization. FK-506 also inhibited K(V)1.5 and K(V)4.3 in a concentration-dependent manner with IC(50) of 4.6 and 53.9 microM, respectively. The present results indicate that FK-506 inhibits K(V)1.3 directly and that this effect is not mediated via the inhibition of the phosphatase activity of calcineurin.
In this study, we report the case of a 59-year-old male patient with organophosphate pesticide poisoning. He visited the local emergency medical center after ingesting 250 ml of organophosphate ...pesticide. The patient’s symptoms improved after the initial intravenous infusion of pralidoxime 5 g and atropine 0.5 mg. However, 18 hours after admission, there was a worsening of the symptoms. A high dose of atropine was administered to improve muscarinic symptoms. A total dose of 5091.4 mg of atropine was used for 30 days, and fever and paralytic ileus appeared as side effects of atropine. Anticholinergic symptoms disappeared only after reducing the atropine dose, and the patient was discharged on the 35th day without any neurologic complications.
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3D8 single-chain Fv (scFv) is a catalytic nucleic acid antibody with anti-viral activity against a broad spectrum of viruses. Here we investigated the functional stability of 3D8 scFv ...to provide a basis for engineering a 3D8 scFv derivative and for developing stable formulations with improved stability and potential use as an anti-viral agent. The stability of 3D8 scFv was assessed by measuring its DNA-hydrolyzing activity under different biochemical and physical conditions using a fluorescence resonance energy transfer (FRET)-based method. In addition, the anti-influenza (H9N2) effect of 3D8 scFv was evaluated in A549 cells. 3D8 scFv was stable at 50°C for 6h at pH 7.2, for 3 days at pH 4–10 at 37°C and 30 days at pH 4–8 at 37°C. The stability was not affected by a reducing condition, freeze–thawing for up to 30 cycles, or lyophilization. Evaluation of the anti-virus effect showed that cells treated with 32–128 units of 3D8 scFv showed a 50% decrease in influenza replication compared to untreated cells. Based on its enzymatic stability in various biochemical and physical environments, 3D8 scFv holds good potential for development as an anti-viral therapeutic.
There is no standard consensus on a strategy in the second-line setting for gemcitabine-refractory advanced pancreatic cancer. This study evaluated the activity and tolerability of oxaliplatin, ...irinotecan, 5-fluorouracil and leucovorin (FOLFIRINOX) as a second-line therapy in advanced pancreatic adenocarcinoma pretreated with a gemcitabine-based regimen.
A retrospective survey was carried out on 18 patients with advanced pancreatic cancer who had been on gemcitabine-based chemotherapy and were then treated with FOLFIRINOX as a second-line therapy.
One patient (5.6%) had a confirmed complete response, 4 (22.2%) had confirmed partial responses and 5 (27.8%) had stable disease, resulting in a rate of disease control of 55.6% (95% CI, 33.3-77.8%). The median progression-free survival and median survival were 2.8 months and 8.4 months, respectively. Seven patients (38.9%) experienced grade 3-4 neutropenia. Grade 3 or 4 nonhematologic adverse events included nausea (38.9%) and vomiting (16.7%).
These results suggest the modest clinical activity regarding efficacy and the acceptable toxicity profile with the FOLFIRINOX regimen as a second-line treatment.
Fuel oil consumption (FOC) must be minimized to determine the economic route of a ship; hence, the ship power must be predicted prior to route planning. For this purpose, a numerical method using ...test results of a model has been widely used. However, predicting ship power using this method is challenging owing to the uncertainty of the model test. An onboard test should be conducted to solve this problem; however, it requires considerable resources and time. Therefore, in this study, a deep feed-forward neural network (DFN) is used to predict ship power using deep learning methods that involve data pattern recognition. To use data in the DFN, the input data and a label (output of prediction) should be configured. In this study, the input data are configured using ocean environmental data (wave height, wave period, wave direction, wind speed, wind direction, and sea surface temperature) and the ship's operational data (draft, speed, and heading). The ship power is selected as the label. In addition, various treatments have been used to improve the prediction accuracy. First, ocean environmental data related to wind and waves are preprocessed using values relative to the ship's velocity. Second, the structure of the DFN is changed based on the characteristics of the input data. Third, the prediction accuracy is analyzed using a combination comprising five hyperparameters (number of hidden layers, number of hidden nodes, learning rate, dropout, and gradient optimizer). Finally, k-means clustering is performed to analyze the effect of the sea state and ship operational status by categorizing it into several models. The performances of various prediction models are compared and analyzed using the DFN in this study.
MicroRNAs (miRNAs) function in mammalian cells via translational repression or messenger RNA (mRNA) cleavage of target genes by base-pairing with 3' untranslated regions (UTRs) of target mRNAs. ...Although miRNAs are involved in cell differentiation or organ development, posttranscritptional regulation of miRNA is not well understood. Here, we developed a dual-luciferase reporter system for monitoring in vivo endogenous transcription of primary miRNA (pri-miRNA) and also the mature miRNA activity simultaneously.
miR23P639/Fluc plasmid carrying firefly luciferase (Fluc) under the control of miR-23a promoter was used to monitor the transcriptional level of miR-23a, and a cytomegalovirus (CMV)/Gluc/3xPT_mir23 recombinant containing 3 copies of the target sequence of miR-23a in the 3' UTR of Gaussia luciferase (Gluc) before the poly(A) tail was used to monitor the targeting activity of mature miR-23a. This dual-luciferase reporter system transfected to the same population of cells was used to monitor the increased transcriptional level of the pri-miR-23a reflected in the Fluc activity and the decreased Gluc activity affected by mature miR-23a action. Fluc and Gluc activities were also imaged in vivo using the respective substrates in grafted cells in the same nude mice using an in vivo bioluminescence imager.
In HeLa cells and undifferentiated P19 cells, the increased Fluc activity representing the primary miR-23a transcript level reflected the resultant increase in repression of Gluc activity representing mature miR-23a activity. However, 293 cells showed Gluc activity was not repressed as much as Fluc activity was increased, suggesting a block in the posttranscriptional processing of miR-23a transcript in 293 cells. The miR-23a expression in P19 cells before and after neuronal differentiation with retinoic acid treatment showed an increase in Fluc activity and a concomitant decrease in Gluc activity in vitro. HeLa, 293 cells and undifferentiated P19 cells grafted to the nude mice showed exactly the same pattern of luciferase activities in vivo and in vitro.
We developed a dual-luciferase reporter system to monitor expression and posttranscriptional regulation of a miR-23a in cells in vitro and in vivo. This dual-luciferase reporter system is intended to be used to monitor the expression and regulation of miRNAs noninvasively, especially to understand the differentiation of grafted cells in vivo.
Glucagon-like peptide-1 and its potent agonist exendin-4 induce several immediate early response genes (IEGs) that code for transcription factors implicated in cell proliferation, differentiation, ...and apoptosis. We recently observed that early growth response factor-1 (EGR-1), an IEG product, was required for transcriptional activation of Ccnd1 (cyclin D1) gene by exendin-4. Herein, the regulatory mechanism whereby exendin-4 activates the transcription of EGR-1 gene was investigated in the pancreatic beta-cell line INS-1. Deletion analysis of rat EGR-1 promoter identified a critical region between -73 and -46 for the activation of EGR-1 in response to exendin-4. Mutation of the proximal putative cAMP response element (CRE, 5'-GTACGTCA-3') located at -69 resulted in a significant decrease in the EGR-1 transcription, whereas the mutation of the distal putative CRE at -139 was without such an effect. In immune supershift assays using exendin-4-treated cells, binding of cAMP response element-binding protein (CREB) phosphorylated on Ser(133) to the proximal CRE was increased. Employment of a CREB mutant containing Ala substitution at Ser(133) or a dominant negative CREB mutant that inhibits the binding of endogenous CREB to DNA significantly decreased the exendin-4-induced EGR-1 transcription. In experiments using specific protein kinase inhibitors, the effect of H-89 was more prominent than PD-98059, indicating the predominance of the PKA signaling over the MEK/ERK in induction of EGR-1. Therefore, it appears that the proximal CRE site is critical and the binding with CREB phosphorylated on Ser(133) is necessary for induction of the EGR-1 transcription by exendin-4.
We evaluated treatment outcomes following single-site repetitive transcranial magnetic stimulation (rTMS) in the dorsolateral prefrontal cortex (DLPFC) and dual-site rTMS in the auditory cortex (AC) ...and DLPFC (AC + FC).
This prospective randomized double-blind trial initially included 19 patients with chronic tinnitus and 17 of these patients received rTMS on the left AC and left DLPFC or only the left DLPFC. The subjects were randomly allocated to either the dual-site rTMS (AC + FC) protocol (Group 1, n = 9) or the singlesite rTMS (DLPFC) protocol (Group 2, n = 8). Group 1 received daily treatments with 2,000 pulses applied to the AC and 1,000 pulses applied to the DLPFC for 4 days (total of 12,000 pulses) and Group 2 received daily treatments with 3,000 pulses applied the DLPFC for 4 days (total of 12,000 pulses).
The severity of tinnitus was assessed before rTMS treatment using the Tinnitus Handicap Inventory (THI) and the self-rated Visual Analog Scale. These measures were used to determine the awareness, loudness, annoyance, and effects of tinnitus on daily life at 1, 2, 4, and 12 weeks after treatment.
The improvement in THI score was significantly better in Group 1 than in Group 2, even after controlling for the between-group differences in pretreatment THI score. In terms of psychological factors, Group 1 exhibited significant improvements in scores on the State-Trait Anxiety Inventory (STAI) for both state anxiety (STAI-X1) and trait anxiety (STAI-X2) at 12 weeks posttreatment and scores on the Pittsburgh Sleep Quality Index at 4 weeks posttreatment. Group 2 showed an improvement in only the STAI-X2 score at 12 weeks posttreatment.
The rTMS protocol effectively suppressed tinnitus in the dual-site rTMS (AC+FC) group but not in the single-site rTMS (DLPFC) group. Although recent evidence has shown that non-auditory cortices in the tinnitus network play an important role in the generation of tinnitus, our findings indicate that rTMS on non-auditory cortical sites alone may not be sufficient for treatment. Thus, dual-site rTMS in the AC and DLPFC may be preferable for controlling this condition.
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