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Next-generation sequencing (NGS) has enabled the high-throughput discovery of germline and somatic mutations. However, NGS-based variant detection is still prone to errors, resulting in inaccurate variant calls. Here, we categorized the variants detected by NGS according to total read depth (TD) and SNP quality (SNPQ), and performed Sanger sequencing with 348 selected non-synonymous single nucleotide variants (SNVs) for validation. Using the SAMtools and GATK algorithms, the validation rate was positively correlated with SNPQ but showed no correlation with TD. In addition, common variants called by both programs had a higher validation rate than caller-specific variants. We further examined several parameters to improve the validation rate, and found that strand bias (SB) was a key parameter. SB in NGS data showed a strong difference between the variants passing validation and those that failed validation, showing a validation rate of more than 92% (filtering cutoff value: alternate allele forward [AF] ≥ 20 and AF<80 in SAMtools, SB<-10 in GATK). Moreover, the validation rate increased significantly (up to 97-99%) when the variant was filtered together with the suggested values of mapping quality (MQ), SNPQ and SB. This detailed and systematic study provides comprehensive recommendations for improving validation rates, saving time and lowering cost in NGS analyses.

Incidence of falling among elderly female has been reported to be much higher than that of elderly male. Although the gender differences in the elderly were reported for the static postural sway, there has been no investigation of the gender difference for the dynamic postural sway. This study investigates how age and gender affect the postural sway during dynamic squat and stand-up movement. 124 subjects (62 subjects for each of young and elderly) performed consecutive squat and stand-up movement, 2 times in one session, and 2 sessions per subject. Center of pressure (COP) was measured using force platform during the test. Outcome measures included peak-to-peak sways of the COP (COP sway) in the sagittal plane (anteroposterior) and frontal plane (mediolateral) and also those normalized by body height. Two-way ANOVA and post-hoc comparisons were performed for the outcome measures with the independent factors of age and gender. All outcome measures, excluding mediolateral COP sway, showed significant interaction of age and gender (p<0.05). Post-hoc test revealed that only female showed increase in COP sway with age. When normalized by height, increase in COP sways (both directions) with age significant only in women resulted in greater sways in elderly female than elderly male. This may be related to the greater fall rate of elderly female than that of elderly men while performing dynamic activities.

Objective: Transforming growth factor beta (TGF-β) plays an important role in tumorigenesis and metastasis. It works as a tumor suppressor in the normal colon, but acts as a cancer promoter during the late stages of colorectal carcinogenesis. High expression of TGF-β is known to be associated with advanced stages, tumor recurrence and decreased survival of patients. We investigated the expression of TGF-β and its signaling axis molecules and evaluated their prognostic significance in patients with stage III rectal cancers., Methods: Tissues from 201 cases of stage III rectal cancer were subjected to immunohistochemistry for TGF-β1, type II TGF-β receptor, Smad3, Smad4 and Smad7 proteins. The immunoactivities of these molecules were evaluated and the results were compared with clinicopathological variables including patient survival., Results: Low expression of TGF-β1 protein was correlated with a decreased disease-free survival in univariate Kaplan-Meier (p = 0.003) and multivariate Cox regression (HR 9.188 and 95% CI 1.256-67.198, p = 0.029) analyses. The loss of Smad4 protein expression was associated with a reduction in disease-free survival in the univariate analysis, but this finding was not significant after the multivariate analysis., Conclusion: Low expression of TGF-β1 protein is associated with a poor prognosis for patients with stage III rectal cancers.

Purpose: The epithelial-mesenchymal transition (EMT) is known to be associated with tumor progression, invasion and metastasis in colorectal cancer (CRC)., Materials and Methods: Tissue samples obtained from 409 patients with stage III CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the expression levels of E-cadherin, fibronectin, vimentin and α-smooth muscle actin (SMA)., Results: Among the 409 patients, 402 cases (98.3%) showed positive E-cadherin expression. Positive E-cadherin expression was associated with well or moderately differentiated cell types and a stable microsatellite status. In multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048), positive perineural invasion (p = 0.002) and negative E-cadherin expression (p = 0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors affecting disease-free survival. The declining E-cadherin expression was associated with a poor outcome in terms of overall survival in univariate (p = 0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI = 0.539-7.296). Fibronectin, vimentin and α-SMA were of no prognostic value in this study., Conclusion: The expression pattern of EMT markers in stage III CRC suggests that declining E-cadherin expression is a possible immunohistochemical predictor of patient prognosis., (© 2014 S. Karger AG, Basel.)

Red ginseng (RG) is the top-selling functional food in Korea, but is not recommended for use in hypertensive patients. This study was performed to determine the pharmacokinetic (PK) interaction between RG and amlodipine, an antihypertensive drug. RG (0, 0.5, 1, or 2 g/kg/d) was administered orally for 2 wk, and then amlodipine (10 mg/kg) was given orally, to Sprague-Dawley (SD) rats. Blood was collected at 0.08, 0.25, 1, 1.5, 2, 3, 6, 12, and 24 h after amlodipine administration. In intravenous (iv) study, RG (0, 1, or 2 g/kg/d) was administered orally to SD rats for 2 wk, followed by amlodipine (2 mg/kg) intravenously (iv). Plasma concentrations of amlodipine were analyzed using a high-pressure liquid chromatography-tandem mass system (LC-MS/MS). Oral administration of amlodipine produced an increase of time to maximum plasma concentration (tmax: 2.6, 4.1, 8.3, and 8.9 h at 0, 0.5, 1, and 2 g/kg/d, respectively), and a decrease of maximum plasma concentration (Cmax: 278.5, 212.4, 232.1, and 238.7 ng/ml at 0, 0.5, 1, and 2 g/kg/d, respectively.). However, the area under the concentration-time curve from time 0 to 24 h measurable concentration (AUC0-24 h was 3487.4, 2895.4, 3158.2, and 3495 ng/h/ml at 0, 0.5, 1, and 2 g/kg/d respectively) was not significantly changed among the different dose groups. Administration of amlodipine iv produced no significant changes in the apparent terminal half-life, volume of distribution, and AUC0-24 hr among the different dose groups. These results suggest that RG induced negligible influence on amlodipine pharmacokinetically in rats.

Community compositions in continental islands have been strongly affected by the connection and separation of land via land bridges during the cycle of glacial and interglacial periods. The biota of the Japanese archipelago is a result of colonization from the adjacent mainland of East Asia via land bridges at the north and south that existed during the Pliocene and in glacial periods during the Pleistocene. The carrion beetle Necrophila jakowlewi (Coleoptera: Silphidae) is discontinuously distributed in inland regions of the East Asian mainland, the Korean Peninsula, the central area of Honshu, Japan, and several adjacent islands. This species is thought to have migrated into Japan via the southern land bridge. We conducted phylogenetic and phylogeographic analyses using a partial sequence of the cytochrome oxidase subunit I gene and estimated the divergence times among populations to elucidate the colonization process of N. jakowlewi into Japan. Populations of N. jakowlewi were estimated to have diverged in the Japanese archipelago during the last glacial period, whereas the related species, N.japonica and N. brunnicollis, diverged during the interglacial or the last glacial period. In N. jakowlewi, most haplotypes were unique to separate regions, suggesting that the regional populations have been segregated from one another without gene flow by geographic isolation due to rising sea level after the last glacial period.

Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence., (Copyright © 2013 AlphaMed Press.)

Various materials, both biological and alloplastic, have been used for mastoid obliteration after canal wall-down mastoidectomy in chronic otitis media. The purpose of this study is to investigate the osteoinductive potential of PCL scaffolds in mastoid obliteration, and to test that osteoinductivity can be enhanced by coating PCL with alginate and rhBMP-2. The in vitro biocompatibilities of the scaffolds were examined using osteoblast-like cells (MG63). Cell-morphology and calcium deposition were assessed. Based on scanning electron microscope (SEM) images, the cells grew sporadically on the surfaces of the struts in the PCL scaffold, while the entire struts of the PCL/alginate/BMP-2 scaffold was covered with the cells. Furthermore, the PCL/alginate/BMP-2 scaffold showed significantly higher calcium deposition than the PCL/alginate scaffold. Micro-CT showed osteogenesis in the pores of the 3D PCL scaffold in the experimental group, compared to the control group. Confocal microscopic findings showed that the honeycomb appearance of the PCL structure remained in the control group (pure PCL), but significant amount of bone remodeling in the experimental group (PCL/alginate/BMP-2). Histomorphometric analysis showed that the experimental group demonstrated a significantly higher amount (p=0.014) of new bone formation with 50.2 ± 6.5% (mean ± SD), compared to 10.2 ± 3.5% for the control group. Based on these in vitro and in vivo results, the use of the PCL/alginate/BMP-2 scaffold seemed to be a promising technique for the mastoid obliteration., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Chronic tympanic membrane (TM) perforation is one of the most common otology complications. Current surgical management of TM perforation includes myringoplasty and tympanoplasty. The purpose of this study was to evaluate the efficacy and feasibility of three dimensional (3D) porous collagen scaffolds with topically applied human umbilical cord serum (UCS) for the regeneration of chronic TM perforation in guinea pigs. To achieve this goal, we fabricated porous 3D collagen scaffolds (avg. strut diameter of 236 ± 51 μm, avg. pore size of 382 ± 67 μm, and a porosity of 96%) by using a 3 axis robot dispensing and low temperature plate systems. Guinea pigs were used in a model of chronic TM perforation. In the experimental group (n=10), 3D collagen scaffold was placed on the perforation and topically applied of UCS every other day for a period of 8 days. The control group ears (n=10) were treated with paper discs and phosphate buffered saline (PBS) only using the same regimen. Healing time, acoustic-mechanical properties, and morphological analysis were performed by otoendoscopy, auditory brainstem response (ABR), single-point laser Doppler vibrometer (LDV), optical coherence tomography (OCT), and light microscopic evaluation. The closure of the TM perforation was achieved in 100% of the experimental group vs. 43% of the control group, and this difference was statistically significant (p=0.034). The ABR threshold at all frequencies of the experimental group was significantly recovered to the normal level compared to the control group. TM vibration velocity in the experimental group recovered similar to the normal control level. The difference is very small and they are not statistically significant below 1 kHz (p=0.074). By OCT and light microscopic examination, regenerated TM of the experimental group showed thickened fibrous and mucosal layer. In contrast, the control group showed absence of fibrous layer like a dimeric TM., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: This study evaluated the expression of p300 in colorectal cancer, its relationship with clinicopathological characteristics, and its potential prognostic significance., Methods: The expression of p300 was measured using immunohistochemistry in tumors and surrounding normal mucosa from 199 patients with primary colorectal cancer. The patients were followed for a median period of 83 months., Results: Nuclear p300 expression was significantly associated with histology (P = 0.031) and lymph node involvement (P = 0.019). When the low and high p300 groups were subdivided according to tumor location, the disease-free survival rate differed only for the patients with colon cancer (P = 0.008). In addition, the disease-free survival significantly differed with p300 expression for stage II disease (P = 0.038), but not for stage III disease. Multivariate analysis revealed that lymph node involvement (P = 0.014) and p300 expression (P = 0.032) were independent predictors of overall survival in adenocarcinomas., Conclusion: The overexpression of p300 may be an independent favorable prognostic factor for disease-free survival in patients with colorectal cancer., (© 2013 Wiley Periodicals, Inc.)

Purpose: Microsatellite instability (MSI) and chromosomal instability are main mechanisms underlying colorectal carcinogenesis. We determined the features and prognosis of colorectal cancer based on MSI including mismatch repair genes and expression of p53., Methods: Between 1999 and 2008, a total of 2,649 colorectal cancer patients were analyzed using a prospective database. A mismatch repair defect (MMR-D) was defined as a loss of expression of more than one MMR protein and/or MSI-high. MMR-proficiency (MMR-P) was defined as expression of all MMR proteins and microsatellite stable (MSS)/MSI-low. Groups 1 (G1), 2 (G2), 3 (G3), and 4 (G4) were defined as MMR-D and p53-positive expression, MMR-D and p53-negative expression, MMR-P and p53-positive expression, MMR-P and p53-negative expression, respectively., Results: Eighty-two (3.0%), 181 (6.8%), 1,368 (51.7%), and 1,018 (38.5%) patients were classified into groups 1-4, respectively. Comparison between G1 and G2 showed differences in location (p < 0.001), size (p = 0.030), node metastasis (p = 0.027), distant metastasis (p = 0.009), and stage (p = 0.040). Comparison between G3 and G4 showed differences in location (p < 0.001) and histology (p < 0.001). Comparison between G1 and G3 showed differences in location (p < 0.001) and histology (p < 0.001). Comparison between G2 and G4 showed differences in age (p < 0.001), location (p < 0.001), size (p = 0.006), histology (p < 0.001), node metastasis (p < 0.001), distant metastasis (p < 0.001), and stage (p < 0.001). On multivariate analysis, stage (p = 0.007) and histology (p < 0.001) were associated with improved overall survival, and stage (p < 0.001) was associated with disease-free survival., Conclusions: According to the MSI and p53 subsets, colorectal cancers showed different clinicopathologic features, but these subsets had no prognostic impact on overall and disease-free survival rate.

The I locus is a 27-kb inverted repeat cluster of chalcone synthase genes CHS1-3-4 that mediates siRNA down-regulation of CHS7 and CHS8 target mRNAs during seed development leading to yellow seed coats lacking anthocyanin pigments. Here, we report small RNA sequencing of ten stages of seed development from a few days post fertilization through maturity, revealing the amplification from primary to secondary short interfering RNAs (siRNAs) occurring during development. The young seed populations had a higher proportion of siRNAs representing the CHS1-3-4 gene family members, consistent with this region as the origin of the primary siRNAs. More intriguingly, the very young seed had a higher proportion of 22-nt CHS siRNAs than did the mid-maturation seed. We infer that the primary CHS siRNAs increase during development to levels sufficient to trigger amplification of secondary CHS siRNAs from the CHS7/8 target mRNAs, enabling the total levels of 21-nt CHS siRNAs to rise dramatically. Further, we demonstrate that the soybean system exhibits tissue-specific CHS siRNA production because primary CHS siRNA levels are not sufficient to trigger secondary amplification in tissues other than the seed coat.

Nanocomposites of iridium nanoparticles (Ir NPs), supported on graphene nanosheets, are synthesized and their electrocatalytic acitivities in the oxygen reduction reaction (ORR) are studied depending on their Ir oxidation state. Graphene functionalized with poly(vinyl pyrrolidone) (pRGO) is a suitable support for Ir NPs, producing well-monodispersed Ir NPs anchored strongly on the pRGO surface (Ir NP/pRGO) with a very high density. This was confirmed by scanning electron microscopy and transmission electron microscopy. The ORR activity of the Ir NP/pRGO nanocomposites in 0.5 M H2SO4 solution was observed to be dependent on the oxidation state of the immobilized Ir NPs. In fact, the nanocomposite composed of Ir(0) metal NPs, rather than Ir oxide (IrOx) NPs, exhibits higher ORR activity, such as more positive onset potential, higher and flatter limiting current density, a greater n value, and a sharper curve shape in the rotating disk electrode voltammetry experiments. Higher ORR activity of Ir is ascribed to the stronger adsorption of oxygen on the surface of Ir compared to IrOx. The practical stability of the Ir NP/pRGO composite was also confirmed under O2 saturated/acidic conditions.

This study sought to investigate the growth rate and organic carbon and nutrient removal efficiency of Chlorella sorokiniana under autotrophic, heterotrophic and mixotrophic conditions. Growth rates of the microalgae were 0.24 d(-1), 0.53 d(-1) and 0.44 d(-1) in autotrophic, heterotrophic and mixotrophic conditions, respectively. The growth rate of C. sorokiniana was significantly higher for that grown under heterotrophic conditions. The nitrogen removal rates were 13.1 mg-N/L/day, 23.9 mg-N/L/day and 19.4 mg-N/L/day, respectively. The phosphorus removal rates reached to 3.4 mg-P/L/day, 5.6 mg-P/L/day and 5.1 mg-P/L/day, respectively. Heterotrophic conditions were superior in terms of the microalgae growth and removal of nitrogen and phosphorus compared to autotrophic and mixotrophic conditions, suggesting that microalgae cultured under this condition would be most useful for application in wastewater treatment systems., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Conclusion: Matrix removal by a non-suction technique with intraoperative dexamethasone injection is a safe and effective management modality, regardless of fistula size., Objective: Our goal was to evaluate the outcome of hearing treated by non-suction technique with intraoperative dexamethasone injection., Methods: This was a retrospective chart review of 720 mastoidectomy cases for cholesteatoma, performed at our tertiary otolaryngologic care centers between 2005 and 2012. A total of 17 patients with a unilateral labyrinthine fistula were encountered., Results: There was no recurrent cholesteatoma in any of the patients. In all cases, the matrix was removed by intraoperative dexamethasone injection with a bimanual non-suction technique, regardless of the fistula size. None of the patients showed deteriorated bone conduction (BC). Averaged BC was unchanged (n = 13) or improved (n = 4) in all patients and did not decrease by 10 dB more in any patient. The mean threshold of postoperative BC was significantly improved compared with preoperative mean threshold. Fistulae on the preoperative CT scans ranged from 1.41 to 7.12 mm and averaged 2.89 mm. There was no correlation between the fistula size and the postoperative BC level. Even with a large fistula, postoperative hearing preservation was possible with one-stage matrix removal.

Certain bacterial zinc-containing anti-sigma (ZAS) factors respond sensitively to thiol-induced oxidative stress by undergoing conformational changes, which in turn reduce binding affinities for their cognate sigma factors. This redox sensitivity provides a mechanism for coping with oxidative stress by activating the transcription of antioxidant genes. Not all ZAS proteins are redox-sensitive, but the mechanism of redox sensitivity is not fully understood. Here we propose that alternative zinc-binding sites determine redox sensitivity. To support this proposal, we performed protein modeling and zinc docking on redox-sensitive and redox-insensitive ZAS proteins complexed with their cognate sigma factors. At least one strong alternative zinc-binding pocket was detected for all known redox-sensitive ZAS factors in actinomycetes, while no strong alternative zinc-binding pocket was identified in redox-insensitive ZAS factors, except for one controversial case. This hypothesis of alternative zinc-binding sites can also explain residue-specific contributions to the redox sensitivity of RsrA, a redox-sensing ZAS protein from Streptomyces coelicolor, for which alanine mutagenesis experiments are available. Our results suggest a mechanistic model for redox sensitivity as follows: zinc ion can probabilistically occupy multiple sites in redox-sensitive ZAS proteins, increasing the susceptibility of zinc-coordinating cysteine residues to oxidation. This picture of probabilistic zinc occupation agrees with a previous structure and energy analysis on zinc finger proteins, and thus it may be more widely applicable to other classes of reactive zinc-binding proteins., (Copyright © 2013 Wiley Periodicals, Inc.)

A series of hollow Pd nanoshells are prepared by employing Co nanoparticles as sacrificial templates with different concentrations of a Pd precursor (1, 6, 12, 20, and 40 mM K2PdCl4), denoted hPd-X (X: concentration of K2PdCl4 in mM unit). The synthesized hPd series are tested as a cathodic electrocatalyst for oxygen reduction reaction (ORR) in alkaline solution. The morphology and surface area of the hPd catalysts are characterized using scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), and cyclic voltammetry (CV). Rotating disk electrode (RDE) voltammetric studies show that the hPd-20 (prepared using 20 mM K2PdCl4) has the highest ORR activity among all the hPd series, while being comparable to commercial Pd and Pt catalysts (E-TEK). The more facilitated ORR at hPd-20 is presumably induced by the enhanced Pd surface area and efficiently high porosity of Pd nanoshells.

Purpose: Clinical implementation of online adaptive radiotherapy requires generation of modified fields and a method of dosimetric verification in a short time. We present a method of treatment field modification to account for patient setup error, and an online method of verification using an independent monitoring system., Methods: The fields are modified by translating each multileaf collimator (MLC) defined aperture in the direction of the patient setup error, and magnifying to account for distance variation to the marked isocentre. A modified version of a previously reported online beam monitoring system, the integral quality monitoring (IQM) system, was investigated for validation of adapted fields. The system consists of a large area ion-chamber with a spatial gradient in electrode separation to provide a spatially sensitive signal for each beam segment, mounted below the MLC, and a calculation algorithm to predict the signal. IMRT plans of ten prostate patients have been modified in response to six randomly chosen setup errors in three orthogonal directions., Results: A total of approximately 49 beams for the modified fields were verified by the IQM system, of which 97% of measured IQM signal agree with the predicted value to within 2%., Conclusions: The modified IQM system was found to be suitable for online verification of adapted treatment fields.

Background: Laparoscopic colectomy for malignancy currently is the standard operative technique together with open colectomy. Single-incision laparoscopic surgery (SIL) is a recent advance in minimally invasive surgical techniques. This study aimed to compare SIL right colectomy with conventional laparoscopy (CL) used to treat patients with colon cancer., Methods: This study was a retrospective analysis of data from the authors' prospectively collected colorectal surgery database. Between August 2009 and November 2010, 159 patients who underwent primary laparoscopic right colectomy at the Samsung Medical Center were recruited to participate in this study. Of these, 66 patients underwent SIL colectomy., Results: The SIL and CL right colectomy groups did not differ significantly in terms of general characteristics including age, sex, body mass index (BMI), American society of anesthesiology (ASA) score, previous abdominal operation, and diagnosis. The two groups also did not differ significantly in terms of perioperative complications (9.1 vs. 15.1 %, p = 0.335). Oncologic resection was similar in the two groups. The mean number of harvested lymph nodes was 24 for SIL and 27 for CL right colectomy (p = 0.068). Tumor size, disease stage, adjuvant chemotherapy, and proximal and distal resection margins did not differ significantly between the two groups. The mean follow-up period was 24.5 for the SIL group and 26.4 months for the CL group (p = 0.098), with six recurrences in the SIL group (9.1 %) and three recurrences in the CL group (3.2 %) (p = 0.120). One death occurred in the CL group. Disease-free survival at 24 months did not differ significantly between the two groups (89.7 vs. 96.3 %, p = 0.120)., Conclusion: The findings show that SIL right colectomy for colon cancer is safe and can provide resection and oncologic outcomes equal to those of conventional laparoscopic right colectomy.

Objective: The application of intratympanic latanoprost (PGF2α analog) has been recently used to alleviate vertigo, disequilibrium and to improve hearing in Meniere's disease patients. However, there is no known report on the effect of topically applied latanoprost on hearing and cochlear hemodynamic parameters including cochlear blood flow (CBF) and vascular conductance. Our goal was to assess the influence of topically applied latanoprost on cochlear blood flow (CBF) and hearing., Materials and Methods: Twenty male Sprague-Dawley rats were randomly divided into the group A, 50 μl of latanoprost (1 ml containing 50 μg, n=10) and group B, 100 μl (1 ml containing 50 μg, n=10). Topical application of latanoprost was performed at the right side, and the left side was applied with phosphate buffered saline (PBS) as a negative control. Five rats at each group were used to measure cochlear blood flow (CBF). And the others at each group were used for hearing test by auditory brainstem response (ABR). After physiological examination, bullas were extracted. The changes of cochlear hair cells were observed by performing the field emission-scanning electron microscopy (FE-SEM)., Results: The CBF of both groups was found to be decreased compared to the PBS applied left side. Significant decrement of CBF was observed in group B compared to the group A. Significant elevation of hearing threshold at high frequencies was observed in both groups compared to the PBS applied group. However, inner and outer hair cells were intact., Conclusion: Topically administered latanoprost decreased the CBF and impaired hearing. Based on our findings, additional studies are required to evaluate the side effects of intratympanic latanoprost before its use in clinical practice., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Intermittent pneumatic compression (IPC) devices have been widely used for thrombosis prophylaxis in laparoscopic colorectal surgery. However, periodic compression using an IPC device may inject augmented boluses of cool blood from the lower limbs into the central circulation repetitively, thereby causing a reduction in core temperature. The authors therefore conducted a prospective, randomized, double-blind, controlled study to compare the effects of intraoperative IPC on core temperature in patients undergoing laparoscopic colorectal surgery., Methods: For this study, 56 patients ages 18-60 years and scheduled to undergo laparoscopic resection for colorectal cancer under general anesthesia were randomly assigned to receive either no IPC (control group) or calf-thigh-length IPC in both legs using the SCD Express (IPC group). Anesthetic, thermal, and pneumoperitoneum management were standardized. Esophageal temperature, as an indicator of core temperature, was measured at 15-min intervals for 2 h after induction of anesthesia., Results: A total of 47 subjects (23 control and 24 IPC subjects) were included in the analysis. The core temperature drop in the IPC group was significantly greater than in the control group, starting from 45 min after induction of anesthesia (P < 0.05). As a result, the total temperature drop during the 2-h study period was significantly greater in the IPC group (1.2 ± 0.3 °C) than in the control group (0.9 ± 0.3 °C) (P = 0.004)., Conclusions: Because intraoperative application of IPC carries an increased risk of a core temperature drop, appropriate temperature monitoring and active thermal management are required for surgical patients receiving IPC.

Two different composite scaffolds, solid-freeform-fabricated PCL/β-TCP supplemented with and without collagen nanofibers are fabricated. These scaffolds are evaluated whether a combination of collagen nanofibers with PCL/β-TCP can promote osteogenesis in a mastoid obliteration. To assess the effects of the cellular activities of osteoblast-like-cells (MG63), SEM images and MTT assays are conducted. Experimental mastoid obliteration is performed using guinea pigs that are divided group A (PCL/β-TCP/collagen-nanofiber scaffold) and group B (PCL/β-TCP scaffold). The results reveal that PCL/β-TCP/collagen scaffold provide much broader cell attachment sites than PCL/β-TCP scaffold. The µ-CT and fluorescent microscopy results reveal that the acceleration of early new bone formation within the pores and scaffold itself at week 4 post-operation is more effective in group A. In addition, based on the results of the histological and µ-CT at 12 weeks post-surgery, the effective regeneration of bone in the PCL/β-TCP/collagen scaffold is appeared., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Purpose: To analyze systematic changes in tumor and normal tissue anatomy and dosimetry using serial MR imaging during pulsed dose rate brachytherapy (PDR BT) for cervical cancer., Material and Methods: Forty-three patients with cervical cancer underwent MR-guided PDR BT using an intrauterine applicator alone after external beam radiotherapy. MR imaging was repeated on days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured volumes., Results: The mean uterine volume and mean HR CTV increased during treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day 1 planned dose. There was no change in the mean bladder volume during treatment but the mean rectal volume increased. This correlated with an increase in the mean rectal dose. There were four local recurrences. There was no apparent relationship between either the planned or the delivered HR CTV D90 and local recurrence. There was only one case of late bladder toxicity but nine patients developed late rectal toxicity. The cumulative rectal dose during treatment was a better predictor of late rectal toxicity than the planned dose., Conclusions: Significant changes in tumor and normal tissue anatomy and dosimetry can occur during PDR BT and should be tracked and corrected using serial imaging and plan adaptation, especially when the day 1 tumor or normal tissue doses are close to the planning constraints., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

There are no previous large scale studies which have evaluated the phenotypes and clinical characteristics of Korean Crohn's disease patients who underwent intestinal resection. The purpose of this multicenter retrospective cohort study was to evaluate the clinical characteristics of Korean Crohn's disease patients who underwent intestinal resection during the study period. A total of 686 patients were enrolled in this study. The study period was over a 20-yr period (1990-2009). The patients were divided into the first-10-yr group and the second-10-yr group. The phenotypes and clinical characteristics were compared between the groups. The most common site of the disease was the ileal area (37.8%) and stricturing behavior was observed in 38.3% patients. The most common type of surgery was segmental resection of the small bowel (30.6%). These phenotypes showed a similar pattern in both the first and second study period groups and did not show any significant differences between the groups. The number of registered patients increased continuously. The phenotypes of Korean Crohn's disease patients who underwent intestinal resection are different compared with previously reported clinical characteristics of general Crohn's disease patients.

The cause and pathogenesis of sudden sensorineural hearing loss (SSNHL) remain unknown. IL-1β is one of the most powerful inflammatory cytokines. The aim of this study was to evaluate the relationships between interleukin-1 β (IL-1β) gene polymorphisms (-511 C/T and +3953 C/T) in patients with SSNHL. One hundred two patients affected by SSNHL and 595 controls were genotyped for IL-1β gene polymorphisms. The polymorphisms were analyzed by polymerase chain reaction amplification and DNA fragment separation via electrophoresis. Compared to controls, the IL-1β (+3953) T allele increased the relative risk of SSNHL in subjects with IL-1β (-511) TT genotype (p = 0.022, OR = 9.111, 95% CI = 1.441-57.618). In this study, polymorphisms in the IL-1β -511 and IL-1β +3953 loci were assessed for evidence of association with SSNHL. From this assessment, a significant difference in carriage of both the IL-1β -511 T allele and the IL-1β +3953 T allele was observed between SSNHL and controls. This suggests that the IL-1β -511 and +3953 loci may play an important role in the etiopathogenesis of SSNHL.

Objective: No study to date has assessed the anti-adhesive effect of new middle ear (ME) packing agents in. This study compared the anti-inflammatory and anti-adhesive effect of antibiotic-steroid containing packing agents in abraded mucosa of the ME inflammation., Materials and Methods: Transbullar injection of a saline suspension of Pseudomonas aeruginosa lipopolysaccharide (LPS) induced otitis media. ME mucosa of guinea pigs was abraded using a pick 30 min after LPS inoculation. The animals were divided into four groups of 10 guinea pigs each. In group A, ME cavity was preserved without any packing. In group B, ME cavity was packed with soluble hyaluronic acid-carboxymethyl cellulose (HA-CMC). In group C, the ME cavity was packed with soluble HA-CMC. In group D, the ME cavity was packed with antibiotic-steroid containing soluble HA-CMC. Otoendoscopic examination, auditory brainstem responses (ABRs), and radiographic examination using computerized tomography (CT) were performed at 2 weeks post-surgery. Histopathological evaluation for ME mucosa was performed by light microscopy (LM) and scanning electron microscopy (SEM)., Results: Otoendoscopic findings and CT findings revealed that group D showed the best recovery of aeration in the ME compared to other groups. Recovery of ABRs threshold was significantly attenuated in group D. In LM and SEM findings, group D showed normalized mucosal thickening compared to other groups., Conclusion: ME packing by antibiotic-steroid containing soluble HA-CMC may be useful in the abraded mucosa of the ME inflammation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Image guidance has improved the precision of fractionated radiation treatment delivery on linear accelerators. Precise radiation delivery is particularly critical when high doses are delivered to complex shapes with steep dose gradients near critical structures, as is the case for intracranial radiosurgery. To reduce potential geometric uncertainties, a cone beam computed tomography (CT) image guidance system was developed in-house to generate high-resolution images of the head at the time of treatment, using a dedicated radiosurgery unit. The performance and initial clinical use of this imaging system are described., Methods and Materials: A kilovoltage cone beam CT system was integrated with a Leksell Gamma Knife Perfexion radiosurgery unit. The X-ray tube and flat-panel detector are mounted on a translational arm, which is parked above the treatment unit when not in use. Upon descent, a rotational axis provides 210° of rotation for cone beam CT scans. Mechanical integrity of the system was evaluated over a 6-month period. Subsequent clinical commissioning included end-to-end testing of targeting performance and subjective image quality performance in phantoms. The system has been used to image 2 patients, 1 of whom received single-fraction radiosurgery and 1 who received 3 fractions, using a relocatable head frame., Results: Images of phantoms demonstrated soft tissue contrast visibility and submillimeter spatial resolution. A contrast difference of 35 HU was easily detected at a calibration dose of 1.2 cGy (center of head phantom). The shape of the mechanical flex vs scan angle was highly reproducible and exhibited <0.2 mm peak-to-peak variation. With a 0.5-mm voxel pitch, the maximum targeting error was 0.4 mm. Images of 2 patients were analyzed offline and submillimeter agreement was confirmed with conventional frame., Conclusions: A cone beam CT image guidance system was successfully adapted to a radiosurgery unit. The system is capable of producing high-resolution images of bone and soft tissue. The system is in clinical use and provides excellent image guidance without invasive frames., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The present study was designed to evaluate the safety and potential of adipose tissue-derived stem cells (ASCs) for the treatment of Crohn's fistula. In this dose escalation study, patients were sequentially enrolled into three dosing groups with at least three patients per group. The first three patients (group 1) were given 1 × 10(7) cells/ml. After 4 weeks, this dose was deemed safe, and so an additional four patients (group 2) were given 2 × 10(7) cells/ml. Four weeks later, after which this second dose was deemed safe, a third and final group of three patients were given 4 × 10(7) cells/ml. Each patient was followed for a minimum of 8 weeks. Patients who showed complete healing at week 8 were followed up for an additional 6 months. Efficacy endpoint was complete healing at week 8 after injection, defined as complete closure of the fistula track and internal and external openings without drainage or signs of inflammation. There were no grade 3 or 4 severity adverse events, and there were no adverse events related to the study drug. Two patients in group 2, treated with 2 × 10(7) ASCs/ml, showed complete healing at week 8 after injection. Of the three patients enrolled in group 3, treated with 4 × 10(7) ASCs/ml, one showed complete healing. Outcome in another patient was assessed as partial healing due to incomplete closure of the external opening, although the inside of fistula track was filled considerably and there was no drainage. All three patients with complete healing at week 8 showed a sustained effect without recurrence 8 months after injection. In conclusion, this study demonstrates the tolerability, safety, and potential efficacy of ASCs for the treatment of Crohn's fistula and provides support for further clinical study.

Background and Objective: Many pharmacological agents have shown successful results in experimental crush injury of the peripheral nerve. To date, therapeutic effect of ginkgo biloba extract (GBE) on the peripheral nerve crush injury of rats has been rarely reported, moreover, neuroprotective effect on the facial nerve crush injury has not been reported., Materials and Methods: Prospective functional recovery, using a vibrissae movement and electrophysiological analysis of recovery 4 weeks after the facial nerve crush in adult rats, and comparison with randomized intraperitoneal injection of either GBE or control phosphate buffered saline., Results: Relative to the control group (26 days post operation), administration of GBE significantly accelerated the recovery of vibrissae orientation to 11.7 days post the operation. A significant functional recovery was observed by postoperative 2nd week in the experimental group. The recovery of threshold and conduction velocity, postoperative 4th week in the experimental group, showed statistically significant difference compared to that of the control group., Conclusion: From this result, intraperitoneal injection of GBE has been found effective in promoting the regeneration of the nerve in an experimental facial nerve crush rat model. Further studies, including morphological and molecular analyses, are necessary to clarify the mechanisms of GBE on the facial nerve crush., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Fast and accurate transit portal dosimetry was investigated by developing a density-scaled layer model of electronic portal imaging device (EPID) and applying it to a clinical environment., Methods: The model was developed for fast Monte Carlo dose calculation. The model was validated through comparison with measurements of dose on EPID using first open beams of varying field sizes under a 20-cm-thick flat phantom. After this basic validation, the model was further tested by applying it to transit dosimetry and dose reconstruction that employed our predetermined dose-response-based algorithm developed earlier. The application employed clinical intensity-modulated beams irradiated on a Rando phantom. The clinical beams were obtained through planning on pelvic regions of the Rando phantom simulating prostate and large pelvis intensity modulated radiation therapy. To enhance agreement between calculations and measurements of dose near penumbral regions, convolution conversion of acquired EPID images was alternatively used. In addition, thickness-dependent image-to-dose calibration factors were generated through measurements of image and calculations of dose in EPID through flat phantoms of various thicknesses. The factors were used to convert acquired images in EPID into dose., Results: For open beam measurements, the model showed agreement with measurements in dose difference better than 2% across open fields. For tests with a Rando phantom, the transit dosimetry measurements were compared with forwardly calculated doses in EPID showing gamma pass rates between 90.8% and 98.8% given 4.5 mm distance-to-agreement (DTA) and 3% dose difference (DD) for all individual beams tried in this study. The reconstructed dose in the phantom was compared with forwardly calculated doses showing pass rates between 93.3% and 100% in isocentric perpendicular planes to the beam direction given 3 mm DTA and 3% DD for all beams. On isocentric axial planes, the pass rates varied between 95.8% and 99.9% for all individual beams and they were 98.2% and 99.9% for the composite beams of the small and large pelvis cases, respectively. Three-dimensional gamma pass rates were 99.0% and 96.4% for the small and large pelvis cases, respectively., Conclusions: The layer model of EPID built for Monte Carlo calculations offered fast (less than 1 min) and accurate calculation for transit dosimety and dose reconstruction.

Background and Study Aims: Transanal endoscopic microsurgery (TEM) has been shown to be highly effective for early rectal cancer, and endoscopic submucosal dissection (ESD) has been introduced to treat noninvasive colorectal neoplasia. The aim of this study was to compare the outcomes of ESD and TEM for superficial early rectal cancer., Patients and Methods: We retrospectively analyzed 63 patients with nonpolypoid rectal high grade dysplasia or submucosa-invading cancer who were treated with ESD or TEM, and compared clinical outcomes and safety between the treatment groups., Results: 30 patients underwent ESD and 33 underwent TEM. For ESD compared with TEM, en bloc resection rates were 96.7% vs. 100% (P = 0.476) and R0 resection rates were 96.7 % vs. 97.0 % (P = 1.000). There were no cases of local recurrence or distant metastasis in either group. Antibiotics were required in 11 patients (36.7%) in the ESD group and 33 (100%) in the TEM group (P < 0.001). There was no difference in net procedure time although ESD was associated with shorter total procedure time and hospital stay than TEM, with mean (standard deviation [SD]) 84.0 (51.2) vs. 116.4 (58.5) min (P = 0.0023), and 3.6 (1.2) vs. 6.6 (3.5) days (P < 0.001), respectively. There were no significant differences in complications between the two groups., Conclusions: Both ESD and TEM are effective and oncologically safe for treating nonpolypoid rectal high grade dysplasia and submucosa-invading cancers. ESD has the additional advantages of minimal invasiveness and avoidance of anesthesia. Therefore, ESD could be recommended as a treatment option for superficial early rectal cancers., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: The study was to compare the shaping ability of Reciproc (VDW) and WaveOne (Dentsply Maillefer) instruments compared with ProTaper, Profile and hand instrument during the preparation of simulated root canals., Materials and Methods: Five groups (n = 5) were established. Reciproc, WaveOne, ProTaper, Profile and K file (K-flexo file) were used to prepare the resin simulated canals. A series of preoperative and postoperative images were taken by a microscope and superimposed in 2 different layers. The amount of resin removed from both the inner and the outer sides of the canal was measured to the level of 10 mm from the apical tip, with a 1 mm increment., Results: The mean of resin removal from the inner canal wall was not different from the outer canal wall for Reciproc and WaveOne groups at apical third (1 - 3 mm level). There was no difference in the change of working length and maintenance of canal curvature. NiTi instruments are superior to stainless-steel K file in their shaping ability., Conclusions: Within the limitation of this present study, Reciproc and WaveOne instruments maintained the original canal curvature in curved canals better than ProTaper and Profile, which tend to transport towards the outer canal wall of the curve in the apical part of the canal.

Objectives: Many materials and surface preparations have been developed to resist the formation of biofilm. Ion-bombarded silicone tympanostomy tube was introduced to resist both staphylococcal and pseudomonal biofilm formation. To date, there are no reports that have evaluated the use of ion-bombarded tympanostomy tubes against the ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilm formation. The purpose of this study is to evaluate the ion-bombarded tympanostomy tube for CRPA biofilm resistance., Methods: Commercial ion-bombarded tympanostomy tubes and simple silicone tympanostomy tubes were processed for an evaluation of the CRPA biofilm formation in vitro., Results: The ion-bombarded tubes showed no resistance to CRPA adhesion and biofilm formation. Thick and dense conglomeration was less formed in the ion-bombarded tympanostomy tubes, compared to that of the simple silicone tube., Conclusion: The preventive effect against the CRPA biofilm formation of the ion-bombarded silicone tympanostomy tube was not observed. Our result suggests that only the surface modification by an ion bombardment is not enough to resist CRPA biofilm formation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Adjuvant chemotherapy is currently recommended for Stage IIIA colon cancers. This study aimed to elucidate the oncologic outcomes of Stage IIIA colon cancer according to the chemotherapeutic regimen based on a retrospective review., Methods: From 1995 to 2008, Stage IIIA colon cancer patients were identified from a prospectively maintained database at a single institution. Exclusion criteria were as follows: rectal cancer, another malignancy other than colon cancer, no adjuvant chemotherapy and unknown chemotherapeutic regimen. One hundred thirty-one patients were enrolled in the study, and the clinicopathologic and the oncologic characteristics were analyzed. The number of males was 72, and the number of females was 59; the mean age was 59.5 years (range, 25 to 76 years), and the median follow-up period was 33 months (range, 2 to 127 months)., Results: Of the 131 patients, fluorouracil/leucovorin (FL)/capecitabine chemotherapy was performed in 109 patients, and FOLFOX chemotherapy was performed in 22 patients. When the patients who received FL/capecitabine chemotherapy and the patients who received FOLFOX chemotherapy were compared, there was no significant difference in the clinicopathologic factors between the two groups. The 5-year overall survival and the 5-year disease-free survival were 97.2% and 94.5% in the FL/capecitabine patient group and 95.5% and 90.9% in the FOLFOX patient group, respectively, and no statistically significant differences were noted between the two groups., Conclusion: Stage IIIA colon cancer showed good oncologic outcomes, and the chemotherapeutic regimen did not seem to affect the oncologic outcome.

Ethnopharmacological Relevance: Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects., Materials and Methods: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid β(1-42) (Aβ(1-42)) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Aβ(1-42) protein-induced astrogliosis or cholinergic neuronal loss in the brain., Results: Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Aβ(1-42) protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Aβ(1-42) protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert., Conclusion: These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Aβ(1-42) protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Although anemia is considered to be a contributor to intra-tumoral hypoxia and tumor resistance to ionizing radiation in cancer patients, the impact of pretreatment anemia on local control after neoadjuvant concurrent chemoradiotherapy (NACRT) and surgery for rectal cancer remains unclear., Materials and Methods: We reviewed the records of 247 patients with locally advanced rectal cancer who were treated with NACRT followed by curative-intent surgery., Results: The patients with anemia before NACRT (36.0%, 89/247) achieved less pathologic complete response (pCR) than those without anemia (p = 0.012). The patients with pretreatment anemia had worse 3-year local control than those without pretreatment anemia (86.0% vs. 95.7%, p = 0.005). Multivariate analysis showed that pretreatment anemia (p = 0.035), pathologic tumor and nodal stage (p = 0.020 and 0.032, respectively) were independently significant factors for local control., Conclusion: Pretreatment anemia had negative impacts on pCR and local control among patients who underwent NACRT and surgery for rectal cancer. Strategies maintaining hemoglobin level within normal range could potentially be used to improve local control in rectal cancer patients.

Purpose: We evaluated the risk factors for late complications and functional outcome after total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)., Methods: Pre- and postoperative clinical status and follow-up data were obtained for 55 patients who underwent TPC with IPAA between 1999 and 2010. The median follow-up duration was 4.17 years. Late complications were defined as those that appeared at least one month after surgery. For a functional assessment, telephone interviews were conducted using the Global Assessment of Functioning Scale. Twenty-eight patients completed the interview., Results: Late complications were found in 20 cases (36.3%), comprising pouchitis (n = 8), bowel obstruction (n = 5), ileitis (n = 3), pouch associated fistula (n = 2), and intra-abdominal infection (n = 2). The preoperative serum albumin level for patients with late complications was lower than for patients without (2.4 ± 0.5 vs. 2.9 ± 0.7, P = 0.04). Functional outcomes were not significantly associated with clinical characteristics, follow-up duration, operation indication, or late complications., Conclusion: This study demonstrated that a low preoperative albumin level could be a risk factor for late complications of TPC with IPAA. Preoperative nutritional support, especially albumin, could reduce late complications. Functional outcomes are not related to late complications.

Purpose: Recently, an increase in well-differentiated rectal neuroendocrine tumors (WRNETs) has been noted. We aimed to evaluate transanal endoscopic microsurgery (TEM) for the treatment of WRNETs., Methods: Between December 1995 and August 2009, 109 patients with WRNETs underwent TEM. TEM was performed for patients with tumors sizes of up to 20 mm and without a lymphadenopathy. These patients had been referred from other clinics after having been diagnosed with WRNETs by using a colonoscopic biopsy; they had undergone a failed endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) and exhibited an involved resection margin and remaining tumor after ESD or EMR, regardless of the distance from the anal verge. This study included 38 patients that had more than three years of follow-up., Results: The mean age of the patients was 51.3 ± 11.9 years, the mean tumor size was 8.0 ± 3.9 mm, and no morbidity occurred. Thirty-five patients were asymptomatic. TEM was performed after a colonoscopic resection in 13 cases because of a positive resection margin, a residual tumor or a non-lifting lesion. Complete resections were performed in 37 patients; one patient with a positive margin was considered surgically complete. In one patient, liver metastasis and a recurrent mesorectal node occurred after five and 10 years, respectively., Conclusion: TEM might provide an accessible and effective treatment either as an initial or as an adjunct after a colonoscopic resection for a WRNET.

In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.

The main cause of death for colorectal cancer (CRC) patients is the development of metastatic lesions at sites distant from the primary tumor. Therefore, it is important to find biomarkers that are related to the metastasis and to study the possible mechanisms. Recent data have shown that soluble attractant molecules called chemokines support the metastasis of certain cancers to certain organs. To identify molecular regulators that are differentially expressed in liver metastasis of CRC, PCR array analysis was performed and CC chemokine ligand 7 (CCL7) showed remarkable overexpression in liver metastatic tumor tissues. To validate the results of the PCR array, 30 patients with primary CRC and liver metastases were selected. Immunohistochemistry and real-time PCR analysis showed that CCL7 was expressed in normal colonic epithelium and the expression was higher in liver metastases compared to primary CRC (p<0.001). Real-time PCR showed that the expression of CCR1, CCR2 and CCR3 was also higher in liver metastases compared to primary CRC (p=0.001, p=0.033 and p<0.001, respectively). In conclusion, correlation of CCL7 overexpression and its receptor expression with colon cancer liver metastasis suggests that CCL7 as a novel target in liver metastasis of CRC may be of potential clinical value for the prevention of hepatic recurrences.

Purpose: The purpose of this study was to assess the risk factors for repeated abdominal surgery in Crohn's disease (CD) patients after the first abdominal surgery. Prior studies have tried to identify the risk factors for postoperative recurrence in CD patients, but the results of the studies have been inconsistent. Furthermore, few data on the risk factors for repeated abdominal surgery are available., Methods: Clinical data on CD patients who underwent abdominal surgery from January 2000 to December 2009 were collected from seventeen university hospitals and one colorectal clinic. Data from a total of 708 patients were analyzed to find the risk factors for repeated abdominal surgery in CD patients. The mean follow-up period was 72 months., Results: The risk of repeated abdominal surgery was 3 times higher in young patients (below 16 years old) than in older patients (odds ratio [OR], 3.056; 95% confidence interval [CI], 1.021 to 9.150); P = 0.046). Stricturing behavior at diagnosis was also a risk factor for repeated abdominal surgery (OR, 2.438; 95% CI, 1.144 to 5.196; P = 0.021). Among operative indications, only intra-abdominal abscess was associated with repeated abdominal surgery (OR, 2.393; 95% CI, 1.098 to 5.216; P = 0.028). Concerning type of operation, an ileostomy might be a risk factor for repeated abdominal surgery (OR, 11.437; 95% CI, 1.451 to 90.124; P = 0.021). Emergency surgery (OR, 4.994; 95% CI, 2.123 to 11.745; P < 0.001) and delayed diagnosis after surgery (OR, 2.339; 95% CI, 1.147 to 4.771; P = 0.019) also increased the risk of repeated abdominal surgery., Conclusion: Young age (below 16 years), stricturing behavior, intra-abdominal abscess, emergency surgery, and delayed diagnosis after surgery were identified as possible risk factors for repeated abdominal surgery in CD patients.

Numerous thiol-reactive compounds cause oxidative stress where cells counteract by activation of survival strategies regulated by thiol-based sensors. In Streptomyces coelicolor, a model actinomycete, a sigma/antisigma pair SigR/RsrA controls the response to thiol-oxidative stress. To unravel its full physiological functions, chromatin immuno-precipitation combined with sequence and transcript analyses were employed to identify 108 SigR target genes in S. coelicolor and to predict orthologous regulons across actinomycetes. In addition to reported genes for thiol homeostasis, protein degradation and ribosome modulation, 64 additional operons were identified suggesting new functions of this global regulator. We demonstrate that SigR maintains the level and activity of the housekeeping sigma factor HrdB during thiol-oxidative stress, a novel strategy for stress responses. We also found that SigR defends cells against UV and thiol-reactive damages, in which repair UvrA takes a part. Using a refined SigR-binding sequence model, SigR orthologues and their targets were predicted in 42 actinomycetes. This revealed a conserved core set of SigR targets to function for thiol homeostasis, protein quality control, possible modulation of transcription and translation, flavin-mediated redox reactions, and Fe-S delivery. The composition of the SigR regulon reveals a robust conserved physiological mechanism to deal with thiol-oxidative stress from bacteria to human., (© 2012 Blackwell Publishing Ltd.)

Background: The NiTi endoluminal Compression Anastomotic Clip (CAC™) 30 (NiTi CAC 30) (NiTi Alloys Technologies, Ltd., Netanya, Israel) is a new device with shape-memory characteristics. We aimed to investigate the safety and early surgical outcomes of NiTi CAC 30 for intestinal anastomosis in patients with gastrointestinal malignancy., Subjects and Methods: Fifty patients operated on with NiTi CAC 30 were matched for sex, age, body mass index, operation type (open versus laparoscopy), operation name, and anastomosis type with patients in a control group operated on with a stapling device between November 2009 and May 2010. Early clinical outcomes were investigated., Results: One misfired case of NiTi CAC 30 was excluded. Between the two groups, no significant differences were observed in demographics except for previous abdominal operation history. The results of early clinical outcomes were investigated, including operation time, estimated blood loss, time to first flatus, first defecation, and discharge, and complications. No differences were noted. Postoperatively, migration started in 1 patient between 3 and 5 days, 11 patients between 6 to 7 days, and 37 patients after 8 days. The expulsion of 31 cases occurred between 2 and 3 weeks, postoperatively. The NiTi CAC 30 was expulsed within 1 week in 4 patients and between 1 to 2 weeks in 8 patients. An expulsion occurred in 1 case at over 4 weeks. No problems related to early migration and expulsion were observed, and no anastomotic leakage and bleeding occurred., Conclusions: Intestinal anastomosis with the NiTi CAC 30 was safe and feasible without anastomotic leakage and reoperation compared with the stapling technique.

Neuroinflammation plays a critical role in the etiology of chronic neurodegenerative diseases such as Alzheimer's disease. INM-176 is a standardized ethanolic extract of Angelica gigas, which has been traditionally used as a tonic to treat anemia. In the present study, we investigated whether INM-176 exhibits neuroprotective activities against lipopolysaccharide (LPS)-induced neuronal damage in vitro and in vivo. In primary microglial cells, INM-176 significantly inhibited LPS-induced nitric oxide release and expression of tumor necrosis factor-α and interleukin-1β. The expression levels of inducible nitric oxide synthase and cylcooxygenase-2 in BV2 microglial cells were markedly upregulated by LPS, but this increased expression was counteracted by INM-176. LPS-mediated neuronal damage in an organotypic hippocampal slice culture was also attenuated by the administration of INM-176. In addition, LPS (1 μg/2 μl, i.c.v.)-induced cognitive dysfunction in mice, as determined by passive avoidance and Y-maze tasks, was significantly attenuated by the administration of INM-176. Furthermore, the activation of microglia or astrocytes by LPS in the hippocampal regions of mice was suppressed by INM-176. These results suggest that the neuroprotective and cognition ameliorating effects of INM-176 against LPS-induced damage are mediated, in part, by its anti-inflammatory activities., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Oxytetracycline and ilomastat are inhibitors of matrix metalloproteinases (MMPs). Their efficacy in protecting against cochlear damage induced by the intratympanic instillation of lipopolysaccharide (LPS), as a means of inducing labyrinthitis, was investigated., Materials and Methods: Experiments were performed in 21 young male guinea pigs. Intratympanic instillation of LPS was done in the control group (n=7). Intratympanic instillation of oxytetracycline or ilomastat was done after LPS instillation in the experimental group. Measurements of auditory brainstem response (ABR) and cochlear blood flow (CBF) were performed. The organ of Corti was evaluated by field emission scanning electron microscopy (FE-SEM). The blood-labyrinth barrier (BLB) integrity was evaluated with Evans blue uptake. Gelatin zymography was used to assess the expression of active MMP-2 and MMP-9., Results: Ears treated with MMP inhibitors were significantly protected from hearing loss compared to the LPS group. In LPS group, there was a significant decrease of CBF. However, experimental group displayed a statistically significant recovery of CBF. FE-SEM revealed hair cell damage in the LPS-treated group, but hair cells presented a normal appearance in MMP inhibitors. The LPS group showed a marked increase of Evans blue extravasation in the cochlea. However, MMP inhibitors significantly reduced the BLB opening. Active MMP-9 was expressed in the LPS group. Treatment with MMP inhibitors attenuated active MMP-9 expression., Conclusion: The MMP inhibitors oxytetracycline and ilomastat protect from cochlear lateral wall damage caused by LPS-induced labyrinthitis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Objectives: The 2010 NCCN clinical practice guidelines recommend radiation as a part of the standard adjuvant or neoadjuvant treatment for stage IV rectal cancer patients. This study evaluated the oncologic efficacy of postoperative radiotherapy (RTx) in loco-regional control after complete removal of primary and metastatic lesions in stage IV rectal cancer., Methods: Sixty-eight patients with metastatic rectal cancer were enrolled and analyzed. Twenty-eight of the enrolled patients received concurrent postoperative RTx with chemotherapy (RTx group) and the remaining 40 received only postoperative systemic chemotherapy (CTx) without RTx (non-RTx group). The eligibility criteria were as follows: a primary rectal tumor located in the low or mid-rectum, no postoperative macroscopic and microscopic evidence of residual tumor in primary and metastatic sites, and no history of prior CTx or pelvic RTx., Results: The recurrence rates were 75.0% in the RTx group and 72.5% in the non-RTx group. Local recurrence rates were 7.1% (RTx group) and 22.5% (non-RTx group) (P = 0.108). There were no differences in overall survival (OS), local recurrence-free survival, and disease-free survival between the two groups. The 2-year OS rates were 78.9% (RTx group) and 74.1% (non-RTx group) (P = 0.395)., Conclusions: Survival benefit of postoperative RTx in stage IV rectal cancer after complete removal of tumors was not apparent. RTx could be recommended for selected patients at high risk of local recurrence or for palliation of symptoms., (Copyright © 2011 Wiley Periodicals, Inc.)

Objectives/hypothesis: The study aimed to regenerate pneumatic air cells in guinea pig bulla using three-dimenisonal (3D) biocomposite scaffolds consisting of polycaprolactone/β-tricalcium phosphate (PCL/β-TCP)., Study Design: Prospective controlled study in experimental animals., Methods: PCL/β-TCP composites were implanted into the bulla with mucosa preservation in group A (n = 10). PCL/β-TCP composites coated with collagen were implanted in group B (n = 10). After 12 weeks, the bullae were extracted and evaluated by micro-computed tomography (micro-CT) and were processed for histological analyses., Results: In group A, micro-CT showed a well-maintained honeycomb appearance of micropores without obstruction. Regeneration of the mucosa was noted inside the pores of the 3D scaffold. However, partial obstruction of the micropores with new bone formation was evident in group B., Conclusions: Group A showed more satisfactory mucosal regeneration into the micropores. Our results indicate that the 3D scaffold may be amenable for use during mastoidectomy. Further studies for gas exchange in the regenerated mucosa are necessary., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)