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Age-related hearing loss (AHL) is the most common form of hearing impairment. AHL is thought to be a multifactorial condition resulting from the interaction of numerous causes including aging, genetics, exposure to noise, and exposure to endogenous and exogenous toxins. Cells possess many detoxification enzymes capable of removing thousands of cytotoxic xenobiotics and endogenous toxins such as 4-hydroxynonenal (4-HNE), one of the most abundant cytotoxic end products of lipid peroxidation. The cellular detoxification system involves three phases of enzymatic detoxification. Of these, the glutathione transferase (GST) detoxification system converts a toxic compound into a less toxic form by conjugating the toxic compound to reduced glutathione by GST enzymes. In this review, we describe the current understanding of the cochlear detoxification system and examine the growing link between GST detoxification, oxidative lipid damage, ototoxicity, and cochlear aging with a particular focus on the alpha-class GSTs (GSTAs). We also describe how exposure to ototoxic drugs, exposure to noise, or aging results in increased 4-HNE levels, how 4-HNE damages various cell components under stress conditions, and how GSTAs detoxify 4-HNE in the auditory system.

Vasculogenic mimicry (VM) is a non-classical mechanism recently described in many tumors, whereby cancer cells, rather than endothelial cells, form blood vessels. Transgelin is an actin-binding protein that has been implicated in multiple stages of cancer development. In this study, we investigated the role of transgelin in VM and assessed its effect on the expression of endothelial and angiogenesis-related genes during VM in MDA-MB-231 breast cancer cells. We confirmed the ability of MDA-MB-231 cells to undergo VM through a tube formation assay. Flow cytometry analysis revealed an increase in the expression of the endothelial-related markers VE-cadherin and CD34 in cells that underwent VM, compared with those growing in a monolayer, which was confirmed by immunocytochemistry. We employed siRNA to silence transgelin, and knockdown efficiency was determined by western blot analyses. Downregulation of transgelin suppressed cell proliferation and tube formation, but increased IL-8 levels in Matrigel cultures. RT-PCR analyses revealed that the expression of IL-8, VE-cadherin, and CD34 was unaffected by transgelin knockdown, indicating that increased IL-8 expression was not due to enhanced transcriptional activity. More importantly, the inhibition of IL-8/CXCR2 signaling also resulted in suppression of VM with increased IL-8 levels, confirming that increased IL-8 levels after transgelin knockdown was due to inhibition of IL-8 uptake. Our findings indicate that transgelin regulates VM by enhancing IL uptake. These observations are relevant to the future development of efficient antivascular agents. Impact statement Vasculogenic mimicry (VM) is an angiogenic-independent mechanism of blood vessel formation whereby aggressive tumor cells undergo formation of capillary-like structures. Thus, interventions aimed at angiogenesis might not target the entire tumor vasculature. A more holistic approach is therefore needed in the development of improved antivascular agents. Transgelin, an actin-binding protein, has been associated with multiple stages of cancer development such as proliferation, migration and invasion, but little is known about its role in vasculogenic mimicry. We present here, an additional mechanism by which transgelin promotes malignancy by way of its association with the occurrence of VM. Although transgelin knockdown did not affect the transcript levels of most of the angiogenesis-related genes in this study, it was associated with the inhibition of the uptake of IL-8, accompanied by suppressed VM, indicating that transgelin is required for VM. These observations are relevant to the future development of efficient antivascular agents.

Achieving accurate and efficacious tumor targeting with minimal off-target effects is of paramount importance in designing diagnostic and therapeutic agents for cancer. In this respect, nanocarriers have gained enormous popularity because of their attainable multifunctional features, as well as tumor-targeting potential by extravasation. However, once administered into the bloodstream, nanocarriers face various in vivo obstacles that may significantly impair their performance needed for clinical translation. Herein, we demonstrate a strategy to enhance tumor-targeting efficiency by embedding functionalities in the interior region of partially PEGylated nanocarriers (ca. 10 nm in diameter), intended for active or passive targeting. The cooperative impact of these topologically inner functional groups (IFGs) was marked: enhancements of >100-fold in IC50 in vitro (e.g., a high-avidity ligand with cationic IFGs) and >2-fold in tumor accumulation at 2 h post-injection in vivo (e.g., a high-avidity ligand with anionic IFGs), both against the fully PEGylated counterpart. Analogous to allosteric modulators, properly employed IFGs may substantially improve the process of effectively directing nanocarriers to tumors, which is otherwise solely dependent on avidity or extravasation.

Regular physical exercise reduces the risk for obesity, cardiovascular diseases, and disability and is associated with longer lifespan expectancy (Taylor et al., 2004; Pahor et al., 2014; Anton et al., 2015; Arem et al., 2015). In contrast, decreased physical function is associated with hearing loss among older adults (Li et al., 2013; Chen et al., 2015). Here, we investigated the effects of long-term voluntary wheel running (WR) on age-related hearing loss (AHL) in CBA/CaJ mice, a well established model of AHL (Zheng et al., 1999). WR activity peaked at 6 months of age (12,280 m/d) and gradually decreased over time. At 24 months of age, the average WR distance was 3987 m/d. Twenty-four-month-old runners had less cochlear hair cell and spiral ganglion neuron loss and better auditory brainstem response thresholds at the low and middle frequencies compared with age-matched, non-WR controls. Gene ontology (GO) enrichment analysis of inner ear tissues from 6-month-old controls and runners revealed that WR resulted in a marked enrichment for GO gene sets associated with immune response, inflammatory response, vascular function, and apoptosis. In agreement with these results, there was reduced stria vascularis (SV) atrophy and reduced loss of capillaries in the SV of old runners versus old controls. Given that SV holds numerous capillaries that are essential for transporting oxygen and nutrients into the cochlea, our findings suggest that long-term exercise delays the progression of AHL by reducing age-related loss of strial capillaries associated with inflammation.SIGNIFICANCE STATEMENTNearly two-thirds of adults aged 70 years or older develop significant age-related hearing loss (AHL), a condition that can lead to social isolation and major communication difficulties. AHL is also associated with decreased physical function among older adults. In the current study, we show that regular exercise slowed AHL and cochlear degeneration significantly in a well established murine model. Our data suggest that regular exercise delays the progression of AHL by reducing age-related loss of strial capillaries associated with inflammation.

Sesquiterpenes are an abundant group belonging to the terpenoid family, with a C15 structure comprise of three isoprene units. Many sesquiterpenes are volatile compounds and it act as chemical messenger in plant signalling, particularly in the defense mechanism against biotic and abiotic stresses. Panax ginseng Meyer is important medicinal herbs with various reported pharmacological efficacies in which its triterpenoid saponins, called ginsenosides, were mostly studied. However, there have been few studies on volatile sesquiterpenes compounds regulation on P. ginseng. As slow-growing perennial plant, P. ginseng received many kind of stresses during its cultivation. The pathogen attack is one of the most devastated perturbation for ginseng yield. Thus, we aimed to analyze P. ginseng STS gene (PgSTS) expressions in ginseng organs as well as mono-, sesquiterpenes contents from ginseng seedlings treated with elicitors. qRT-PCR and GC-MS analysis showed that two elicitors- salicylic acid (SA) and methyl jasmonate (MeJA) triggered PgSTS expression at different time points and significantly induced mono-, sesquiterpene yield. Overexpression of PgSTS in Arabidopsis also induced high terpene content and conferred tolerance against Pseudomonas syringae pv. tomato infection. These results suggested that PgSTS transcripts are involved in terpenoid biosynthesis in response to environmental stress mediated by MeJA and SA elicitors; thus, generate tolerance against pathogen attack.

Purpose This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen. Materials and Methods Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m2 intravenously (IV) on D1 (D), docetaxel 60 mg/m2 IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m2 IV D1 plus oral S-1 30 mg/m2 twice a day on D1-14 (DS). Results Seventy-two patients were randomized to the D (n=23), DC (n=24), or DS (n=25) group. The confirmed response rate was 4.3% (95% confidence interval [CI], 0% to 12.6%), 4.3% (95% CI, 0% to 12.6%), and 8.7% (95% CI, 0% to 20.2%) for the D, DC, and DS groups, respectively. Compared to the D arm, the DS arm had a better progression-free survival (2.7 months vs. 1.3 months, p=0.034) without any deterioration in safety or quality of life, whereas the DC arm had a similar progression-free survival (1.8 months vs. 1.3 months, p=0.804) and poorer overall survival (5.6 months vs. 10.0 months, p=0.035). Conclusion A re-challenge with S-1, but not cisplatin, in combination with docetaxel has potential anticancer benefits over docetaxel alone in MGC with progression after prior cisplatin plus S-1 or capecitabine.

Background and Purpose— Dissection is an increasingly recognized cause of ischemic stroke, which occurs spontaneously or after trauma, in relatively young patients. We hypothesized that there might be a predisposing factor weakening the vascular wall and that arterial tortuosity might be higher in patients with dissection. Methods— We consecutively enrolled cervical artery dissection (CerAD) patients who had undergone magnetic resonance angiography. Age- and sex-matched healthy subjects who underwent magnetic resonance angiography in a routine health examination were used as controls. The tortuosity was measured semiautomatically from the carotid artery and vertebral artery (VA) arteries. Tortuosity index was defined as: [(arc/chord)−1×100] in each arteries. Independent risk factors associated with CerAD were investigated using multivariable analysis. Subgroup analysis according to the dissected artery was performed. Results— There were no differences in vascular risk factors between the 75 CerAD patients and the 75 controls. The tortuosity indexes of the contralesional VA (16.3±6.8 versus 12.1±4.5, respectively; P P =0.01) were higher in patients with CerAD compared with those of control subjects. VA tortuosity (odds ratio, 1.175; P =0.001) was independently associated with the presence of CerAD. In subgroup analysis, VA tortuosity was significantly higher in 57 patients with VA dissection than in controls ( P P =0.05). Conclusions— CerAD is associated with tortuous cervical arteries, which may implicate weakened cervical vascular structure in these patients.

Utilization Analysis of Neonatal Red Blood Cell Aliquots and Development of Electronic Issuing System Minjeong Nam, Mi Jung Kim, Soon He Choi, Yun Ji Hong, Hyungsuk Kim, Sang Mee Hwang, Jeong Su Park, Chang Won Choi, Kyoung Un Park, Junghan Song, Kyou Sup Han Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Departments of Laboratory Medicine and Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea

Hearing gradually declines with age in both animals and humans and this condition is known as age-related hearing loss. Here, we investigated the effects of deficiency of Sirt1, a member of the mammalian sirtuin family, on age-related cochlear pathology and associated hearing loss in C57BL/6 mice, a mouse model of early-onset age-related hearing loss. Sirt1 deficiency reduced age-related oxidative damage of cochlear hair cells and spiral ganglion neurons, and delayed the early onset of age-related hearing loss. In cultured mouse inner ear cell lines, Sirt1 knockdown increased cell viability under oxidative stress conditions, induced nuclear translocation of Foxo3a, and increased acetylation status of Foxo3a. This resulted in increased activity of the antioxidant enzyme catalase. In young wild-type mice, both Sirt1 and Foxo3a proteins resided in the cytoplasm of the supporting cells within the organ of Corti of the cochlea. Therefore, our findings suggest that SIRT1 promotes early-onset age-related hearing loss through suppressing FOXO3a-mediated oxidative stress resistance in the cochlea of C57BL/6 mice.

Although endoscopic submucosal dissection has been shown to be safe and effective for colorectal tumors, its clinical outcomes vary.The aim of this study is to assess the outcomes of endoscopic submucosal dissection according to clinical indications.This is a prospective, multicenter, single-arm study.The study was conducted at special hospitals for colorectal diseases and cancers.The study population included consecutive patients aged 20 to 80 years who underwent colorectal endoscopic submucosal dissection for 1) early colorectal cancer, 2) laterally spreading tumors ≥2 cm in diameter, and 3) submucosal tumors.Procedures were performed by experienced colonoscopists.The primary end points were en bloc and curative resection rates. En bloc resection was defined as endoscopic one-piece resection without tumor fragmentation. Curative resection was defined as en bloc resection and no pathologic requirement for additional surgery. Secondary end points included procedure time, complications, and hospital stay.Of 321 patients, 317 (98.8%) underwent en bloc resection and 231 (72.0%) underwent curative resection. The mean procedure time was 46.2 minutes. Mean hospital stay after the procedure was 3.1 days. Perforation occurred in 2 patients (0.6%), and bleeding occurred in 10 (3.1%) patients. All patients with complications were treated by endoscopic clipping or nonoperative management. Fifteen patients (4.7%) underwent additional radical surgery owing to the risks of lymph node metastasis. Although tumor size was smaller and procedure time shorter in the submucosal tumor group than in the laterally spreading tumor or early colorectal cancer group, there were no differences in clinical outcomes including en bloc and curative resection rates. Submucosal fibrosis was the only factor affecting endoscopic submucosal dissection procedure-related complications.Early outcomes in a limited population and the potential for selection bias were limitations of this study.Outcomes of colorectal endoscopic submucosal dissection were acceptable in selected patients, with no difference in outcomes according to clinical indications. Because submucosal fibrosis can increase complications, it should be minimized before endoscopic submucosal dissection.

AIMS The aim of this study was to determine whether human mutL homologue 1 (hMLH1) inactivation precedes the progression of sessile serrated lesion (SSL) into SSL with cytological dysplasia (SSL/D) and to define the histological stage at which promoter methylation and inactivation of hMLH1 occur. METHODS AND RESULTS Using the MassARRAY EpiTYPER assay and immunohistochemistry, we examined methylation levels and the protein expression status of hMLH1 in 33 SSL/Ds with conventional epithelial dysplasia and compared the results with those of control hyperplastic polyps (HPs) and SSLs. The methylation level of hMLH1 was higher in the dysplastic component than in the non-dysplastic component of SSL/Ds (P = 0.005), and differed significantly with regard to the degree of dysplasia (P = 0.002). The methylation levels of hMLH1 in the dysplastic component of SSL/Ds tended to be higher than those of control SSLs and HPs (P = 0.063 and P = 0.017, respectively). The loss of hMLH1 protein expression was identified in only 13 of 33 (39.39%) dysplastic components of SSL/Ds. CONCLUSION Promoter methylation and loss of protein expression of hMLH1 are not parallel processes that occur concurrently. hMLH1 methylation is an early molecular event which occurs even in HP. However, the loss of hMLH1 expression is a much later step, found in approximately 40% of SSL/Ds at various histological stages. Notably, the loss of hMLH1 protein expression does not necessarily precede the development of cytological dysplasia in SSL.

The development of wearable sensors is aimed at enabling continuous real-time health monitoring, which leads to timely and precise diagnosis anytime and anywhere. Unlike conventional wearable sensors that are somewhat bulky, rigid, and planar, research for next-generation wearable sensors has been focused on establishing fully-wearable systems. To attain such excellent wearability while providing accurate and reliable measurements, fabrication strategies should include (1) proper choices of materials and structural designs, (2) constructing efficient wireless power and data transmission systems, and (3) developing highly-integrated sensing systems. Herein, we discuss recent advances in wearable devices for non-invasive sensing, with focuses on materials design, nano/microfabrication, sensors, wireless technologies, and the integration of those.

Purpose The purpose of this study was to develop a measurement tool for a positive nursing organizational culture and to verify its reliability and validity. Methods A conceptual framework and construct factors were extracted through an extensive literature review and indepth interviews with nurses. The final version of the preliminary tool for the main survey was confirmed by experts through a content validity test and a preliminary survey of 40 nurses. Subsequently, the final tool was developed using a validity and reliability test containing 43 preliminary items. The final version of the tool was used with 327 hospital nurses in the testing phase for the main survey to assess validity and reliability. Results From the factor analysis, 4 factors and 26 items were selected. The factors were positive leadership of the nursing unit manager, pursuit of common values, formation of organizational relationships based on trust, and a fair management system. The entire determination coefficient was 67.7%. These factors were verified through convergent, discriminant, and concurrent validity testing. The internal consistency reliability was acceptable (Cronbach's α = .95). Conclusion Both the validity and reliability of the scale were confirmed demonstrating its utility for measuring positive nursing organizational culture. It is expected to be used for education, research, and practical performance policies regarding the nursing organizational culture.

BackgroundFalling is one of the leading causes of injury among elderly populations. As the population over 65 years old increases, medical costs due to falling will also increase. Urban and rural areas have different fall characteristics, and research into these differences is lacking.MethodsA survey was conducted on 2,012 people over 60 years old between September 1, 2015 to October 12, 2015. Guro-gu (Seoul), Yeongdeungpo-gu (Seoul), and Jung-gu (Daegu) were classified as urban areas and included 1,205 of the study participants. Dalseong-gun (Daegu) and Yangpyeong-gun (Gyeonggi-do) were categorized as rural areas and included 807 participants. Several region characteristics, including population density, were considered to distinguish between urban and rural areas. The survey included questions about fall history, cause, season and time of recent falls, and external conditions associated with recent falls, like floor or ground material and shoe types.ResultsRural respondents were older than urban respondents (pConclusionsA fall-prevention program that reflects the characteristics and differences of falls in urban and rural areas should be developed and used to effectively prevent falling among elderly people.

Thioredoxin 2 (TXN2) is a small redox protein found in nearly all organisms. As a mitochondrial member of the thioredoxin antioxidant defense system, TXN2 interacts with peroxiredoxin 3 (PRDX3) to remove hydrogen peroxide. Accordingly, TXN2 is thought to play an important role in maintaining the appropriate mitochondrial redox environment and protecting the mitochondrial components against oxidative stress. In the current study, we investigated the effects of Txn2 haplodeficiency on cochlear antioxidant defenses, auditory function, and cochlear cell loss across the lifespan in wild-type (WT) and Txn2 heterozygous knockout (Txn2+/−) mice backcrossed onto CBA/CaJ mice, a well-established model of age-related hearing loss. Txn2+/− mice displayed a 58% decrease in TXN2 protein levels in the mitochondria of the inner ears compared to WT mice. However, Txn2 haplodeficiency did not affect the thioredoxin or glutathione antioxidant defense in both the mitochondria and cytosol of the inner ears of young mice. There were no differences in the levels of mitochondrial biogenesis markers, mitochondrial DNA content, or oxidative DNA and protein damage markers in the inner ears between young WT and Txn2+/− mice. In a mouse inner ear cell line, knockdown of Txn2 did not affect cell viability under hydrogen peroxide treatment. Consistent with the tissue and cell line results, there were no differences in hair cell loss or spiral ganglion neuron density between WT and Txn2+/− mice at 3–5 or 23–25 months of age. Furthermore, Txn2 haplodeficiency did not affect auditory brainstem response threshold, wave I latency, or wave I amplitude at 3–5, 15–16, or 23–25 months of age. Therefore, Txn2 haplodeficiency does not affect cochlear antioxidant defenses, accelerate degeneration of cochlear cells, or affect auditory function in mice across the lifespan.

Here we report a novel method of microRNA (miRNA) profiling with particle-based multiplex quantitative reverse transcription polymerase chain reaction (RT-qPCR). To achieve target-specific reaction in a particle, the stem-loop RT primer and forward primer for each target miRNA were chemically immobilized to the particle. Target-specific cDNA synthesis proceeds with the stem-loop RT primer and then qPCR subsequently proceeds with the forward primer to rapidly achieve a quantitative result. High-fidelity multiplex assay was also accomplished in a single PCR process by loading multiple particles for each specific miRNA. The method for primer supply in the particles, involving confinement of the target-specific RT and PCR primers in the matrix of particles, led to the reduction of nonspecific reactions and improved the selectivity of the miRNA assay while minimizing labor in a multiple target assay. Specifically, this particle-based assay enabled the differentiation of mature miRNA from precursor with selectivity of 270:1 in terms of amplification speed. This advanced method also showed good discrimination among highly homologous let-7 family members, with cross-reaction rates of less than 5%. We demonstrated a very simple process of five-plex miRNA profiling in total RNA, and the measured changes in expression level were consistent with those from a conventional singleplex method.

Purpose Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial. Patients and Methods We developed a novel deep learning–based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data. Results The mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone. Conclusion Our SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.

Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in a variety of age-related neurodegenerative diseases, including age-related hearing loss (AHL). In the current study, we investigated the roles of mtDNA deletions and point mutations in AHL in mitochondrial mutator mice (Polg(mut/mut)) that were backcrossed onto CBA/CaJ mice, a well-established model of late-onset AHL. mtDNA deletions accumulated significantly with age in the inner ears of Polg(mut/mut) mice, while there were no differences in mtDNA deletion frequencies in the inner ears between 5 and 17 months old Polg(+/+) mice or 5 months old Polg(+/+) and Polg(mut/mut) mice. mtDNA deletions also accumulated significantly in the inner ears of CBA/CaJ mice during normal aging. In contrast, 5 months old Polg(mut/mut) mice displayed a 238-fold increase in mtDNA point mutation frequencies in the inner ears compared to age-matched Polg(+/+) mice, but there were no differences in mtDNA point mutation frequencies in the inner ears between 5 and 17 months old Polg(mut/mut) mice. Seventeen-month-old Polg(mut/mut) mice also displayed early-onset severe hearing loss associated with a significant reduction in neural output of the cochlea, while age-matched Polg(+/+) mice displayed little or no hearing impairment. Consistent with the physiological and mtDNA deletion test result, 17-month-old Polg(mut/mut) mice displayed a profound loss of spiral ganglion neurons in the cochlea. Thus, our data suggest that a higher burden of mtDNA point mutations from a young age and age-related accumulation of mtDNA deletions likely contribute to early-onset AHL in mitochondrial mutator mice.

Background: Advances in the field of interventional and diagnostic radiology have resulted in anesthesiologists becoming involved in angiographic suites. In the present study, we evaluated the characteristics of patients and the anesthetic management in an angiographic suite, to determine what factors influenced the patient outcome. Methods: Data pertaining to patients that were anesthetized at an angiographic suite in a university hospital between 1 January 2007 and 31 December 2007 were evaluated retrospectively. Specifically, we evaluated the patient characteristics and the types of anesthesia administered, to determine which factors were related to patient outcome. Results: Sixty-four percent of the patients enrolled in this study were women. Cases involving coiling for unruptured and ruptured aneurysm, embolization for intracranial arteriovenous malformation and fistula, pediatric diagnostic angiography, embolization for extracranial arteriovenous malformation, and implantable cardioverter-defibrillator (ICD) implantation all required the involvement of anesthesiologists. Major postoperatve complications included pneumonia, atelectasis, and hydrocephalus. In addition, GCS, net fluid balance, and anesthesia time had influence on patient outcome. Conclusions: We evaluated the characteristics of patient groups, procedures, and postoperative complications in an angiographic suite. The results of our analysis revealed that a through understanding of nervous and vascular pathology, as well as knowledge of current interventional radiology, neuroanesthesia and vascular anesthesia techniques is essential for development of safe and effective care. (Korean J Anesthesiol 2009;56:36~46)

The number of elderly patients with end-stage renal disease on maintenance dialysis therapy is gradually increasing. The elderly population has difficulties in making decisions regarding initiation of dialysis treatment because of their high morbidity and frailty. The purpose of this study was to determine the best prognostic tool in predicting short-term mortality in elderly patients undergoing dialysis. This study is a multicenter retrospective study. We enrolled patients, aged ≥ 75 years, who began hemodialysis at three university hospitals in Korea from January 2010 to December 2016. We applied two comorbidity-based score tools (Thamer and Wick, each consisting of seven variables) and the Clinical Frailty Scale (CFS, seven scales), which were validated for mortality prediction in elderly incident patients. Patient’s information was obtained from electronic medical records in the participating center, and mortality data (up to December 2016) were obtained from the Korean National Statistical Office. Models were compared using the area under the receiver operating characteristic curve. Among the 219 patients enrolled in this study, the 3- and 6-month mortality rates were 31 (14.4%) and 48 (22.4%), respectively. Receiver operating characteristic curve analysis revealed that both score systems and the CFS showed similar performance while predicting 3- and 6-month mortality. The scores from these indices correlated with survival time. Predicting short-term mortality and long-term survival time for elderly patients is possible using the Thamer and Wick scores and the CFS.

The purpose of this study is to prospectively compare the image quality of and confidence in the presence of a lesion on CT urography images acquired using filtered back projection (FBP) with 100% and 50% radiation doses with those for images simultaneously acquired using sinogram-affirmed iterative reconstruction with strength 3 (SAFIRE) with 50% and 25% radiation doses for patients with a high risk for urothelial carcinomas.A total of 150 patients randomly underwent CT urography examinations performed using a dual-source single-energy scanner. After the radiation output of each tube was adjusted, datasets at three radiation dose levels were reconstructed using FBP and SAFIRE. Seven radiologists subjectively assessed image quality and confidence in the presence of a lesion for a total of 1200 datasets. Nonparametric methods for cluster data were used to estimate AUC values for variance methods on the basis of a noninferiority margin of 0.05.The mean AUC value for image quality in SAFIRE with a 25% radiation dose was significantly lower than that of FBP with 100% radiation dose (p0.05 for all). The mean AUC values for the presence of a lesion were 0.907 and 0.894 for FBP, respectively, at 100% and 50% radiation doses, respectively, and 0.900 and 0.799 for SAFIRE at 50% and 25% radiation doses, respectively. However, the image quality of images acquired with SAFIRE at a 25% radiation dose was significantly inferior to that of images acquired with FBP at a 100% radiation dose.Regardless of the experience of the radiologist, CT urography images acquired with FBP and SAFIRE with a 50% radiation dose were noninferior to those acquired with FBP with a 100% radiation dose in terms of image quality and confidence in the presence of a lesion, whereas those acquired with SAFIRE with 25% radiation dose were inferior.

Proliferative and migratory abilities of fibroblasts are essential for wound healing at the skin surface. Cytoplasmic linker-associated protein-2 (CLASP2) was originally found to interact with cytoplasmic linker protein (CLIP)-170. CLASP2 plays an important role in microtubule stabilization and the microtubule-stabilizing activity of CLASP2 depends on its interactions with end binding (EB)-1 and CLIP-170. Although the microtubule-stabilizing role of CLASP2 is well established, the effects of CLASP2 on the migration and proliferation of fibroblasts remain unclear in the context of wound healing. Therefore, we tested the utilization of CLASP2 as a directly applied protein drug to improve wound healing by promoting the migration of effector cells, including skin fibroblasts, to the site of repair or injury using an in vivo excisional wound mouse model and in vitro Hs27 skin fibroblast model. Epidermal growth factor, which is a recognized contributor to cell proliferation and migration, was used as positive control. In vitro and in vivo, CLASP2 treatment significantly enhanced cell migration and accelerated wound closure. Furthermore, in vivo, the CLASP2-treated animal group displayed enhanced epidermal repair and collagen deposition. Next, we studied the mechanism of CLASP2 for wound healing. Increasing the abundance of intracellular free CLASP2 in skin fibroblasts by supplying exogenous CLASP2 seemed to stabilize microtubules through an interaction between CLASP2 and CLIP-170, as well as EB1. Exogenous CLASP2 also showed direct binding with IQGAP1, increasing both cyclic adenosine monophosphate activity and phosphorylation of glycogen synthase kinase 3β, which in turn reinstated the binding between free CLASP2 and IQGAP1. In summary, exogenous CLASP2 increased Hs27 skin fibroblast migration by interacting with IQGAP1 and other cytoskeletal linker proteins, such as CLIP-170 and EB1. Our results strongly suggest that CLASP2 can be developed in wound healing drugs for skin repair and/or regenerating cosmetic products.

Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH. In the mitochondria, IDH2 also plays a key role in protecting mitochondrial components from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates age-related hearing loss, the most common form of hearing impairment, in male mice. This was accompanied by increased oxidative DNA damage, increased apoptotic cell death, and profound loss of spiral ganglion neurons and hair cells in the cochlea of 24-month-old Idh2−/− mice. In young male mice, loss of Idh2 resulted in decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the inner ear. In HEI-OC1 mouse inner ear cell lines, knockdown of Idh2 resulted in a decline in cell viability and mitochondrial oxygen consumption. This was accompanied by decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the HEI-OC1 cells. Therefore, IDH2 functions as the principal source of NADPH for the mitochondrial thioredoxin antioxidant defense and plays an essential role in protecting hair cells and neurons against oxidative stress in the cochlea of male mice.

PURPOSE Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

Here we demonstrate fully-integrated, bezel-less transistor arrays using stretchable origami substrates and foldable conducting interconnects. Reversible folding of these arrays is enabled by origami substrates which are composed of rigid support fixtures and foldable elastic joints. In addition, hybrid structures of thin metal films and metallic nanowires worked as foldable interconnects which are located on the elastomeric joints.

Background Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals. Objectives We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD. Methods We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity. Results No difference was seen in the enteric α-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P

Insulin and insulin-like growth factor contribute to normal brain function. Recent experimental and clinical studies showed that type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD) or Alzheimer's disease (AD) share several dysregulated pathways.We aimed to investigate whether genome-wide significant loci of T2DM are associated with the risk of PD and AD as well as the severity of cognitive impairment.Study subjects were 500 PD patients, 400 AD patients, and 500 unrelated controls. We selected 32 genetic variants from 11 genes (CDC123, CDKAL1, CDKN2B, FTO, GLIS3, HHEX, IGF2BP2, KCNJ11, KCNQ1, SLC30A8, and TCF7L2) and intergenic regions based on results of recent genome-wide association studies (GWAS) in T2DM. These variants were reported to be T2DM-susceptibility loci and have been replicated in other independent studies. All association analyses were performed using logistic regression models, adjusting for age and sex.KCNQ1 SNP rs163182 showed the strongest association with AD, but it was not significant after Bonferroni correction (OR = 1.30, 95% CI = 1.07-1.59, Pcorrected = 0.32). In PD patients, CDC123 SNP rs11257655 showed modest association with MMSE score26, and CDKN2B SNPs (rs2383208, rs10965250, and rs10811661) showed modest association with MoCA score26, which were not significant after Bonferroni correction. Other genetic variants had no association with the risk of PD or AD and the severity of cognitive impairment.Our results suggest that genome-wide significant loci of T2DM play no major role in the risk and cognitive impairment of PD and AD.

Buckwheat (Fagopyrum esculentum MOENCH) is a traditional Korean crop that gaining global attention as a health food due to its rich nutrition. Climate change effects such as high temperature, cold weather, flooding, and drought induce plant stress, reduced production yield of upland crops. In general, buckwheat is grown during the fall season in Korea. Flooding is a severe environmental stress factor, and flooding during the early growth stage of buckwheat causes large reductions in yield. Therefore, we established optimum growth parameters to maximize buckwheat yield. The optimum temperature for harvesting of buckwheat was approximately 1,083 ~ 1,515°C. The number of growing degree days (G.D.D.) from flowering to harvest was 509 ~ 673°C. Plant hight, stem diameter, and dry matter weight were reduced as planting date was delayed (p < 0.05). We investigated buckwheat sowing time during fall, and established an optimum cropping system according to the local climate conditions in central Korea. The growth period of buckwheat cultivar ‘Yangjueol’ was approximately 56 ~ 60 days during fall, and yield was higher than that of cultivar ‘Daesan’. The results indicated that buckwheat yield in central Korea was maximized by sowing cultivar on 25th August and cultivar ‘Daesan’ on 15th August. The yield of Yangjeol sown in spring was 119 kg 10a-1, whereas the yield of Daesan sown in summer was 158kg 10a-1. The results of this study established the effects of sowing time on growth and yield in central Korea. We propose an optimum cropping system for improving quality.

Objective To compare the pain-reducing effect of forest bathing alone versus forest bathing in combination with stretching and strengthening exercises in patients with chronic posterior neck pain. Methods Sixty-four subjects with posterior neck pain that had lasted more than 3 months were enrolled. They were randomly divided into a forest bathing alone (FBA) group and a forest bathing with exercise (FBE) group; each group included 32 subjects. All subjects from both groups walked every morning in the forest for about 2 hours for 5 days. In the afternoon, the FBE group did a stretching and strengthening exercise for about 4 hours; the FBA group had free time in the woods. Visual analog scale (VAS) on one day, VAS over the previous week, neck disability index (NDI), EuroQol 5D-3L VAS (EQ VAS) and index (EQ index), McGill pain questionnaire (MPQ), the number of trigger points in the posterior neck region (TRPs), and the range of motion of the cervical spine were evaluated on the first and last day of the program and compared between the two groups. Results The number of TRPs were significantly reduced in the FBE group compared with the FBA group (p=0.013). However, the other scales showed no significant difference between the two groups. Conclusion When patients with chronic posterior neck pain underwent a short-term forest bathing (less than 7 days) program, FBE was more effective in the reduction of the number of TRPs than FBA. However, all other pain measurement scales we evaluated showed no statistically significant difference between the two protocols.

Fading test using the single aliquot additive dose method with pulsed optically stimulated luminescence (SAAD-POSL method) was applied to core–disc samples extracted from heated red brick, tile, roof-tile, and toilet porcelain after X-ray and beta irradiation. From thermoluminescence measurements of each material, the optimal preheat condition of the SAAD-POSL method was first determined as 170 °C for 10 s. Fading characteristics of core–disc samples of heated red brick obtained using the SAAD-POSL method were similar to those of quartz grains (90–250 μm) obtained using the SAR-OSL method, regardless of the differences in the sample and radiation type. Fading evaluations of the core–disc samples of these building materials two weeks after irradiation showed that the equivalent dose (ED) decreased between 5% and 42%. The results indicate that the fading characteristics will be able to contribute to a more accurate estimation of the ED value using the SAAD-POSL method.

Background and Purpose— With the increased investigation of cerebral arteries using magnetic resonance angiography in the general population, the detection of unruptured intracranial aneurysms (UIAs) has increased. Understanding the distribution and factors associated with UIAs might be helpful for understanding the pathomechanism. Methods— Subjects who underwent magnetic resonance angiography with a health examination at the Health Screening and Promotion Center were enrolled. The incidence and risk factors of UIAs (age, sex, hypertension, diabetes mellitus, smoking, alcohol, and coronary artery disease) were investigated by comparing patients with and without UIAs. These risk factors were also investigated by the UIA location, distal internal carotid artery, anterior cerebral artery and middle cerebral artery (MCA), MCA bifurcation, anterior and posterior communicating artery, and posterior circulation. Results— Among 187 166 subjects who received health examination, 18 954 underwent magnetic resonance angiography. Of them, 367 (1.93%) had UIAs. Age (odds ratio [OR], 1.02; P =0.003), women (OR, 2.00; P P P =0.001), and coronary artery disease (OR, 0.23; P Conclusions— The risk factors for UIAs differ by their location, compared with the control. Interestingly, the presence of coronary artery disease was protective against the presence of UIAs.

The aim of the present study was to investigate the ear and kernel characteristics of colored waxy corn hybrids during ripening according to different sowing dates. Heukjinjuchal and Eolrukchal 1 were sown at April 20 (first cropping) and July 20 (second cropping) in 2011~2012. The accumulated temperature from silking to harvesting was about 590~610℃. It takes 23~24 days when Heukjinjuchal and Eolrukchal 1 were sown in April 20, but July 20 sowing takes 32~35 days. Ear weight, ear diameter, 100-kernel weight and starch content of colored waxy corn were increased as ears matured (p

Conventional gait rehabilitation requires at least three therapists in a traditional rehabilitation training program. Several robots have been developed to reduce human burden and increase rehabilitation efficacy. In this study, we present a lower-limb wearable robot (WA-H) for gait rehabilitation of hemiplegia patients, and propose a protocol of 12 weeks gait rehabilitation training program using WA-H. To identify the efficacy of the robot and protocols, we conducted a clinical study with two actual hemiplegia patients and observed a chronological change of ambulation ability through four assessments. We discovered the progression of results by 6 minute walking test, TUGT (Timed Up and Go Test), SPPB (Short Physical Performance Battery), BBS (Berg Balance Test), and Fugl-Meyer score. The torques generated in the normal side and paralyzed side of the patient became similar, indicating rehabilitation. The result also showed the walking of the paralysis patient improved and imbalance motion had considerable improved performance.

Objective To apply tailored rehabilitation education to video display terminal (VDT) workers with musculoskeletal pain and to assess changes in musculoskeletal pain after rehabilitation education. Methods A total of 8,828 VDT workers were screened for musculoskeletal disorders using a self-report questionnaire. Six hundred twenty-six VDT workers selected based on their questionnaires were enrolled in musculoskeletal rehabilitation education, which consisted of education on VDT syndrome and confirmed diseases, exercise therapy including self-stretching and strengthening, and posture correction. One year later, a follow-up screening survey was performed on 316 VDT workers, and the results were compared with the previous data. Results Compared with the initial survey, pain intensity was significantly decreased in the neck area; pain duration and frequency were significantly decreased in the low back area; and pain duration, intensity, and frequency were significantly decreased in the shoulder and wrist after tailored rehabilitation education. In addition, pain duration, intensity, and frequency showed a greater significant decrease after tailored rehabilitation education in the mild pain group than in the severe pain group. Conclusions This study found that work-related musculoskeletal pain was reduced after tailored rehabilitation education, especially in the shoulder, wrist, and low back.

Effective treatment of diabetic neuropathy (DN) remains unsolved. We serendipitously observed dramatic relief of pain in several patients with painful DN receiving granulocyte-colony stimulating factor (G-CSF). The aim of this study was to determine if G-CSF could treat DN in an animal model and to ascertain its mechanism of action. In a rodent model of DN, G-CSF dramatically recovered nerve function, retarded histological nerve changes and increased the expression of neurotrophic factors within nerve. A sex-mismatched bone marrow transplantation (BMT) study revealed that G-CSF treatment increased the abundance of bone marrow (BM)-derived cells in nerves damaged by DN. However, we did not observe evidence of transdifferentiation or cell fusion of BM-derived cells. The beneficial effects of G-CSF were dependent on the integrity of BM. In conclusion, G-CSF produced a therapeutic effect in a rodent model of DN, which was attributed, at least in part, to the actions of BM-derived cells.