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Posterior neck pain is a common complaint of patients in the pain clinic. The atlas (C1) burst fracture is known to be a cause of posterior neck pain and instability. Although the atlas burst fracture and instability can be discovered by plain X-rays which show lateral mass displacement or widening of the atlantodental interval, assessment of an atlas burst fracture can be difficult if there is no instability in the imaging study. Here we report a case of a 46-year-old female patient who had complained of sustained posterior neck pain for 6 months. Plain X-rays showed only disc space narrowing at C4/5 and C5/6, without any cervical instability. However, an unrecognized C1 lateral mass fracture was detected by CT and MRI. The patient's pain was then successfully treated after atlantoaxial joint injection with a C2 DRG block.

Using a coupled ocean–atmosphere general circulation model, we investigated the impact of Greenland ice sheet melting on North Atlantic climate variability. The positive-degree day (PDD) method was incorporated into the model to control continental ice melting (PDD run). Models with and without the PDD method produce a realistic pattern of North Atlantic sea surface temperature (SST) variability that fluctuates from decadal to multidecadal periods. However, the interdecadal variability in PDD run is significantly dominated in the longer time scale compared to that in the run without PDD method. The main oscillatory feature in these experiments likely resembles the density-driven oscillatory mode. A reduction in the ocean density over the subpolar Atlantic results in suppression of the Atlantic Meridional Overturning Circulation (AMOC), leading to a cold SST due to a weakening of northward heat transport. The decreased surface evaporation associated with the cold SST further reduces the ocean density and thus, simultaneously acts as a positive feedback mechanism. The southward meridional current associated with the suppressed AMOC causes a positive tendency in the ocean density through density advection, which accounts for the phase transition of this oscillatory mode. The Greenland ice melting process reduces the mean meridional current and meridional density gradient because of additional fresh water flux, which suppress the delayed negative feedback due to meridional density advection. As a result, the oscillation period becomes longer and the transition is more delayed.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of prostaglandin E2 (PGE2) to a biologically inactive keto metabolite 15-keto-PGE2. However, the molecular mechanisms underlying regulation of 15-PGDH expression remain largely elusive. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor γ, has been reported to have anti-inflammatory and anti-carcinogenic activities. In the present study, we have found that 15-PGJ2 upregulates expression and catalytic activity of 15-PGDH in human breast cancer (MDA-MB-231) cells. 15d-PGJ2 treatment decreased the CpG methylation in the 15-PGDH promoter in MDA-MB-231 cells as determined by the bisulfite genome sequencing and methyl-specific PCR. 15d-PGJ2 inhibited catalytic activity of methyltransferase 1 (DNMT1) but did not influence DNMT expression. 15d-PGJ2 increased the expression of c-Fos which is a functional subunit of AP-1. Chromatin-immunoprecipitation analysis revealed that 15d-PGJ2 significantly attenuated DNMT1 binding to the site for AP-1 transcription factor present in the 15-PGDH promoter regions, while increasing c-Fos binding. Biotin-tagged 15d-PGJ2 directly bound to DNMT1, and reduced its catalytic activity. A non-electrophilic analogue 9,10-dihydro-15d-PGJ2 failed to suppress the methylation of CpG islands present in 15-PGDH promoter and did not affect both DNMT1 activity and 15-PGDH expression. This findings suggests that the α,β-unsaturated carbonyl group of 15d-PGJ2 is essential for its inactivation of DNMT1 and expression of 15-PGDH. In conclusion, 15d-PGJ2 directly interacts with DNMT1 and consequently suppresses DNMT1-mediated hypermethylation of 15-PGDH promoter, leading to upregulation of 15-PGDH expression. Citation Format: Hye-Ok Jang, Hye-Rim Kim Kim, Ha-Na Lee, Do-Hee Kim, Young-Joon Surh, Hye-Kyung Na. Upregulation of 15-hydroxyprostaglandin dehydrogenase expression by 15-Deoxy-Δ12,14-prostaglandin J2 through inactivation of DNA methyltransferase 1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 273.

New blood vessel formation is essential for tissue regeneration to deliver oxygen and nutrients and to maintain tissue metabolism. In the field of tissue engineering, in vitro fabrication of new artificial vessels has been a longstanding challenge. Here we developed a technique to reconstruct a microvascular system using a polycaprolactone (PCL)/gelatin nanofibrous structure and a co-culture system. Using a simple electrospinning process, we fabricated three-dimensional mesh scaffolds to support the sprouting of human umbilical vein endothelial cells (HUVECs) along the electrospun nanofiber. The co-culture with adipose-derived mesenchymal stem cells (ADSCs) supported greater sprouting of endothelial cells (ECs). In a two-dimensional culture system, angiogenic cell assembly produced more effective direct intercellular interactions and paracrine signaling from ADSCs to assist in the vascular formation of ECs, compared to the influence of growth factor. Although vascular endothelial growth factor and sphingosine-1-phosphate were present during the culture period, the presence of ADSCs was the most important factor for the construction of a cell-assembled structure in the two-dimensional culture system. On the contrary, HUVECs co-cultured on PCL/gelatin nanofiber scaffolds produced mature and functional microvessel and luminal structures with a greater expression of vascular markers, including platelet endothelial cell adhesion molecule-1 and podocalyxin. Furthermore, both angiogenic factors and cellular interactions with ADSCs through direct contact and paracrine molecules contributed to the formation of enhanced engineered blood vessel structures. It is expected that the co-culture system of HUVECs and ADSCs on bioengineered PCL/gelatin nanofibrous scaffolds will promote robust and functional microvessel structures and will be valuable for the regeneration of tissue with restored blood vessels.

Electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) has become an invaluable tool for the selective and sensitive detection of cationic and anionic species, including charged drug molecules and proteins. In addition, neutral molecules can also be detected at the ITIES via enzymatic reactions. This chapter highlights recent developments towards creating a wide spectrum of sensing platforms involving ion transfer across the ITIES. As well as outlining the basic principles needed for performing these sensing applications, the development of ITIES-based detection strategies for inorganic, organic, and biological ions is discussed.

The anticancer properties of MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, in various human cancer cell lines have been previously reported. The aim of the present study was to investigate the activities of MHY-449 on human lung cancer cells in order to elucidate its underlying molecular mechanisms of action. The result showed that MHY-449 treatment inhibited cell growth in a time- and concentration‑dependent manner. Specifically, MHY-449 induced cell cycle arrest at the S phase, and the resulting increased sub-G1 fraction led to the induction of apoptosis, as determined by flow cytometric analysis and DNA fragmentation. In addition, MHY-449 was shown to induce alterations in the ratio of Bax/Bcl-2 protein expression, and contribute to the loss of mitochondrial membrane potential. These cellular events then triggered the caspase cascade and subsequent poly(ADP‑ribose) polymerase cleavage. The apoptotic cell death induced by MHY-449 was inhibited by pretreatment with Z-VAD‑FMK, a pan-caspase inhibitor. Moreover, MHY-449 downregulated the phosphorylation of Akt, and the phosphatidylinositol-3 kinase/Akt inhibitor LY294002 was found to enhance its induction of apoptosis. Taken together, the results suggested that MHY-449 exerts anticancer effects by promoting cell cycle arrest and apoptosis via the downregulation of Akt. Based on these data, MHY-449 serves as a potential candidate in the chemoprevention and/or treatment of lung cancer.

Mammalian cells have cytoplasmic and mitochondrial aminoacyl-tRNA synthetases (ARSs) that catalyze aminoacylation of tRNAs during protein synthesis. Despite their housekeeping functions in protein synthesis, recently, ARSs and ARS-interacting multifunctional proteins (AIMPs) have been shown to play important roles in disease pathogenesis through their interactions with disease-related molecules. However, there are lacks of data resources and analytical tools that can be used to examine disease associations of ARS/AIMPs. Here, we developed an Integrated Database for ARSs (IDA), a resource database including cancer genomic/proteomic and interaction data of ARS/AIMPs. IDA includes mRNA expression, somatic mutation, copy number variation and phosphorylation data of ARS/AIMPs and their interacting proteins in various cancers. IDA further includes an array of analytical tools for exploration of disease association of ARS/AIMPs, identification of disease-associated ARS/AIMP interactors and reconstruction of ARS-dependent disease-perturbed network models. Therefore, IDA provides both comprehensive data resources and analytical tools for understanding potential roles of ARS/AIMPs in cancers. Database URL: http://ida.biocon.re.kr/, http://ars.biocon.re.kr/

Endotracheal tube (ETT) positioning using the cuff ballottement test, which confirms that the inflated cuff is positioned at the suprasternal notch with squeezing or inflating a pilot balloon, has been reported to be a simple and reliable method of preventing endobronchial intubation. However, in patients with a short vocal cord-to-suprasternal notch, ETT placement using the cuff ballottement test can cause vocal cord injury. In the present study, we assessed the distance from a point 15 mm below the vocal cord to the suprasternal notch (VSD-15), the safe position for ETT cuff placement above the suprasternal notch, and investigated variables for predicting VSD-15.We retrospectively examined neck computed tomography in 427 adult patients and measured VSD-15 and the distance from the thyroid notch to the suprasternal notch (TSD). Patient height, weight, sex, and age were also recorded.In total, 47 patients (11.0%) showed a VSD-15 shorter than 45 mm. VSD-15 significantly correlated with TSD (r = 0.778, P

Purpose: The aim of this study was to explore the patients` perspectives on nursing students` clinical practices in the wards, and to investigate their willingness for allowing students to practice on them. Methods: This was a descriptive study. 116 inpatients were recruited from the S University Hospital. A 60-item questionnaire was applied to collect the data. The participants were 19 years and older with sound judgement, and were not in special or intensive care units. Data analysis was done in SPSS/WIN 22.0 using descriptive statistics, Fishers exact test, and the ANOVA test. the participant answered to questionnaire from April 29th 2016 to May 10th. Results: 40 participants (34.5%) stated they would allow students` practice, while 72 (61.2%) said they would allow only under staff supervision. 5 participants (4.3%) stated they would not allow whatsoever. The 3 most allowed were emotional support, oral care, and vital signs measurement while the 3 least allowed were gastric feeding, intravenous catheterization, and urinary catheterization. Conclusion: Patients were more inclined to allow students to practice on them when a member of the medical team was present. A fair number of participants said they would be more inclined to allow students` practice if they felt the student was competent; hence, reinforcing simulation sessions is vital in enhancing students` competency and ultimately practice allowance.

Tyrosinase inhibitors might have potential use in cosmetic and medicinal products for the prevention of pigmentation disorders. However, only a few inhibitors are currently used due to their cytotoxicity, and lack of selectivity and stability. In this study, we synthesized several tyrosinase inhibitors and investigated their activity. To investigate the action of 2-[4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy]-2-methylpropanoic acid (MHY908) specifically in the inhibition of melanogenesis, a mushroom tyrosinase activity assay was performed. We confirmed the inhibitory effect of MHY908 at various melanin concentrations using α-MSH-induced melanoma cells. Our results indicate that MHY908 potently inhibited mushroom tyrosinase activity (IC50 = 8.19 μM) in a dose-dependent manner. Through a docking simulation, we also analyzed its binding mode to inhibit tyrosinase activity. MHY908 also decreased melanin synthesis without inducing cytotoxicity. These results suggest that MHY908 is a good candidate for prevention and treatment of pigmentation disorders.

Insulin resistance is common with aging and is associated with the inflammatory response in both humans and rodents. A number of peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have been tested for their abilities to attenuate insulin resistance and type 2 diabetes. However, there is no study on the effects of PPARα/γ dual agonists on inflammation and insulin resistance during aging. In the present study, we investigated the ability of 2-[4-(5-chlorobenzothiazothiazol-2-yl)phenoxy]-2-methyl-propionic acid (MHY908), a newly synthesized novel PPARα/γ dual agonist, to suppress the inflammatory response and attenuate insulin resistance in aged rats. Twenty-month-old rats were divided into four groups: ad libitum fed, ad libitum fed supplemented with MHY908 (1 mg and 3 mg/kg/day for 4 weeks), and 40% calorie restricted. Six-month-old ad libitum fed rats were used as an age control. The aged rats supplemented with MHY908 showed reduced serum glucose, triglyceride, and insulin levels, as well as reduced liver triglyceride levels. MHY908 brought about a reduction in endoplasmic reticulum stress and activation of the c-Jun N-terminal kinase in the livers of aged rats, which consequently improved insulin signaling. In the kidneys of aged rats, the efficacy of MHY908 as a potent anti-inflammatory agent was shown by its suppression of NF-κB activation through inhibition of the Akt/IκB kinase signaling pathway. Therefore, the major finding of this study is that MHY908 acts as a therapeutic agent against age-related inflammation associated with insulin resistance by activating PPARα and PPARγ, thus attenuating endoplasmic reticulum stress.

Unguarded tricuspid regurgitation (TR) due to a flail tricuspid leaflet is a rare condition of newborn cyanosis. A high perinatal mortality has been associated with this fatal condition. But, there are feasible surgical repairs to improve survival. We report the case of a male full-term neonate with intractable hypoxia. He had profound tricuspid insufficiency and leaflet prolapse caused by a ruptured papillary muscle supporting the anterior leaflet of the tricuspid valve. He presented with severe cyanosis and respiratory distress immediately after birth. Despite medical management, the pulmonary vascular resistance was not decreased and a low cardiac output persisted. Initial stabilization was accomplished with nitric oxide and extracorporeal membrane oxygenation. The tricuspid valve repair surgery was successfully performed subsequently. TR resulting from papillary muscle rupture is a potentially lethal condition. Timely diagnosis and proper surgical treatment can be lifesaving.

Ultraviolet B (UVB; 290~320nm) irradiation-induced lipid peroxidation induces inflammatory responses that lead to skin wrinkle formation and epidermal thickening. Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have the potential to be used as anti-wrinkle agents because they inhibit inflammatory response and lipid peroxidation. In this study, we evaluated the function of 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl) phenol (MHY 966), a novel synthetic PPAR α/γ dual agonist, and investigated its anti-inflammatory and anti-lipid peroxidation effects. The action of MHY 966 as a PPAR α/γ dual agonist was also determined in vitro by reporter gene assay. Additionally, 8-week-old melanin-possessing hairless mice 2 (HRM2) were exposed to 150 mJ/cm(2) UVB every other day for 17 days and MHY 966 was simultaneously pre-treated every day for 17 days to investigate the molecular mechanisms involved. MHY 966 was found to stimulate the transcriptional activities of both PPAR α and γ. In HRM2 mice, we found that the skins of mice exposed to UVB showed significantly increased pro-inflammatory mediator levels (NF-κB, iNOS, and COX-2) and increased lipid peroxidation, whereas MHY 966 co-treatment down-regulated these effects of UVB by activating PPAR α and γ. Thus, the present study shows that MHY 966 exhibits beneficial effects on inflammatory responses and lipid peroxidation by simultaneously activating PPAR α and γ. The major finding of this study is that MHY 966 demonstrates potential as an agent against wrinkle formation associated with chronic UVB exposure.

Although human lysyl-tRNA synthetase (KRS), an enzyme for protein synthesis, is often highly expressed in various cancer cells, its pathophysiological implications have not been understood. Here we found that KRS induces cancer cell migration through interaction with the 67-kDa laminin receptor (67LR) that is converted from ribosomal subunit p40. On laminin signal, KRS was phosphorylated at the T52 residue by p38MAPK and dissociated from the cytosolic multi-tRNA synthetase complex for membrane translocation. The importance of T52 phosphorylation for membrane translocation of KRS was confirmed by site-directed mutagenesis. In the membrane, turnover of 67LR was controlled by Nedd4-mediated ubiquitination, and KRS inhibited ubiquitin-dependent degradation of 67LR, thereby enhancing laminin-induced cell migration. This work thus unveiled a unique function of KRS in the control of cell migration and its pathological implication in metastasis.—Kim, D. G., Choi, J. W., Lee, J. Y., Kim, H., Oh, Y. S., Lee, J. W.,...

Femoral veins are commonly used as a relatively safe alternative route for central venous cannulation. Several maneuvers are used to increase the cross-sectional area of the vein. In this study, we assessed the effect of positive end-expiratory pressure (PEEP) on the cross-sectional area (CSA) of femoral veins, using ultrasound in adult patients under positive pressure ventilation. All patients received a standardized induction of general anesthesia and intravenous fluid administration. Using ultrasound, the cross-sectional areas of both femoral veins were measured in 57 adult patients in the supine position without PEEP (control) and in the supine position with PEEP of 10 cm H(2)O. Mean arterial pressure and heart rate were recorded before and after the application of PEEP at 10 cm H(2)O. The application of 10 cm H(2)O PEEP significantly increased the CSA of the right femoral vein by 47.6 % and the left femoral vein by 48.4 % (each P0.001). Mean arterial pressure decreased by 2.6 mmHg (95 % CI 1.3-3.9; P0.001), whereas no significant change in heart rate was observed (P = 0.861). The CSA of the femoral vein is augmented with the application of 10 cm H(2)O PEEP in adult patients undergoing positive pressure ventilation.

To obtain high resolution imaging of exo-solar planet, a novel design for a space-borne system is developed. It consists of a constellation of 24 light collection units located near the Earth-Sun L2 libration point. Optimal formation strategy is selected as two Golay 12 static arrays by simulating the imaging performance of several strategies. Each light collector is a truss-mounted Bracewell interferometer for starlight nulling, the output of which is recorded by a photodetector. Digitized photodetector data from all light collection units is then transmitted and processed to compute the image using the Intensity Correlation Imaging (ICI) approach. A target of our design is “super-Earths” in the habitable zones of M-class stars. This stellar class is the most abundant and the contrast ratio in mid infrared for habitable zone super-Earth is most favorable. Our goal is to create images having 20 pixels across the diameter of planets within 10 parsecs of Earth. To meet the requirement for unblurred images, the total imaging time need to be less than 1/20 th the planet rotation period.

Mammalian methionyl-tRNA synthetase (MRS) plays an essential role in initiating translation by transferring Met to initiator tRNA (tRNA i Met ). MRS also provides a cytosolic anchoring site for aminoacyl-tRNA synthetase-interacting multifunctional protein-3 (AIMP3)/p18, a potent tumor suppressor that is translocated to the nucleus for DNA repair upon DNA damage. However, the mechanism by which this enzyme mediates these two seemingly unrelated functions is unknown. Here we demonstrate that AIMP3 is released from MRS by UV irradiation-induced stress. Dissociation was induced by phosphorylation of MRS at Ser662 by general control nonrepressed-2 (GCN2) following UV irradiation. Substitution of Ser662 to Asp (S662D) induced a conformational change in MRS and significantly reduced its interaction with AIMP3. This mutant possessed significantly reduced MRS catalytic activity because of loss of tRNA Met binding, resulting in down-regulation of global translation. According to the Met incorporation assay using stable HeLa cells expressing MRS S662A or eukaryotic initiation factor-2 subunit-α (eIF2α) S51A, inactivation of GCN2-induced phosphorylation at eIF2α or MRS augmented the role of the other, suggesting a cross-talk between MRS and eIF2α for efficient translational inhibition. This work reveals a unique mode of regulation of global translation as mediated by aminoacyl-tRNA synthetase, specifically MRS, which we herein identified as a previously unidentified GCN2 substrate. In addition, our research suggests a dual role for MRS: ( i ) as a coregulator with eIF2α for GCN2-mediated translational inhibition; and ( ii ) as a coupler of translational inhibition and DNA repair following DNA damage by releasing bound tumor suppressor AIMP3 for its nuclear translocation.

Conjugation of chitosan with nucleobases is expected to expand its not only antimicrobial activity but also anti-cancer activity. Here, we report the synthesis of a novel chitosan-thymine conjugate by the reaction between chitosan and thymine-1-yl-acetic acid followed by acylation. The synthesized conjugate was characterized by FTIR, XRD, (1)H NMR, TGA and SEM. The microbiological screening results demonstrated the antimicrobial activity of the conjugate against bacteria viz., Escherichia coli, Staphylococcus aureus, and fungi viz., Aspergillus niger. The chitosan-thymine conjugate also inhibited (p

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This paper presents a new analytical model of surge dynamics in turbo heat pumps. Turbo heat pumps use refrigerants as the working fluid and consist of a centrifugal compressor, condenser, expansion valve, and evaporator. Compared to a gas turbine engine, the turbo heat pump system introduces additional complexities. First, the turbo heat pump forms a closed-loop system. Second, the system has two plenums — condenser and evaporator — which are coupled to each other. Third, the heat pump runs on a refrigeration cycle with two phases — vapor and liquid. Fourth, heat transfer effects of evaporation and condensation have to be considered. Fifth, unlike air, a refrigerant has strong real gas effects and thus cannot be modeled as an ideal gas. The new model addresses such additional complexities on the basis of the first principles of conservation of mass, momentum, and energy. When applied to a gas turbine system, the new model’s predictions become identical to those from the Greitzer’s model. Furthermore, comparison with the available experimental data shows that the model can also accurately predict surge behavior in actual turbo heat pumps. Finally, the effects of Greitzer’s B parameter and the ratio of evaporator and condenser volume have been examined. Parameter B influences both surge shape and frequency. Finally, surge frequency is extremely sensitive to the ratio of the two plenum volumes.Copyright © 2010 by ASME

Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target., Author Summary Lung cancer is one of the most common cancers and a leading cause of death resulting from cancer. Despite intensive investigation, effective therapeutic targets and reliable biomarkers are still limited. Here we found that a tumor suppressor, AIMP2 (MSC p38), produces a variant lacking a part of its structure in cancer tissues. We designated it AIMP2-DX2. This smaller version of AIMP2 compromises the normal tumor suppressive activity of AIMP2 and induces tumor formation. We also found that the expression of AIMP2-DX2 was increased according to cancer progression. In addition, the patients with higher expression of AIMP2-DX2 showed lower survival than those with lower levels of this variant. Suppression of AIMP2-DX2 slowed tumor growth, suggesting it as a new therapeutic target. In summary, this work newly identified a tumor-inducing factor, AIMP2-DX2, that can be used as a therapeutic target and biomarker associated with lung cancer.

BACKGROUND Implantation of xenogenic chromaffin cells into the spinal subarachnoid space can produce analgesia in neuropathic pain models. However, transplantation of xenogeneic chromaffin cell has a potential risk of viral or bacterial infections from animals to humans including encephalopathy due to prion transmission. The aim of this study was to investigate the possibility of developing a homogeneic source of therapeutic chromaffin cells. METHODS Anti-allodynic effects of human chromaffin cells (HCCs) were evaluated in a neuropathic pain model in rats induced by chronic constriction injury of the sciatic nerve. HCCs encapsulated with alginate-poly-L-lysine-alginate were intrathecally implanted into rats (n = 10), while empty capsules were intrathecally implanted as a control (n = 8). Levels of norepinephrine from encapsulated HCCs before and after nicotinic stimulation were measured. We then perfomed a behavior test (cold allodynia) with acetone. In addition, to assess the potential contribution to pain reduction of opioid peptides released from the HCCs, all animals were injected with naloxone. RESULTS The concentration of norepinephrine after nicotine stimulation was significantly increased compared to basal levels. Intrathecal implantation of encapsulated HCCs, significantly reduced cold allodynia as compared to rats receiving empty capsules (P < 0.05). Fifteen minutes after the injection of naloxone, cold allodynia significantly decreased in rats with HCCs (P < 0.05), while the degree of cold allodynia in control animals was unaltered. CONCLUSIONS From these results, it appears that HCCs have a possibility as an analgesic source for transplants delivering pain-reducing neuroactive substances.

To investigate the pattern of non-cancer deaths and to determine whether there is excess mortality from non-cancer causes among Korean long-term survivors of adult cancer.We merged national cancer registry data and national death registration data to determine non-cancer death patterns of 243,713 people who were diagnosed with cancer from 1993 to 2000 and who survivedor =5 years. We calculated standardized mortality ratios (SMRs) by an indirect standardization method.Of the patient population, 26,498 (10.9%) had died as of December 2005; the cause of death for 6,364 (24.0%) of those was not cancer. The proportion of non-cancer mortality increased with age at diagnosis and correlated with the 5-year survival rate (r = 0.336 for women, 0.571 for men). Although the risk for non-cancer death was lower among long-term survivors in general (SMR, 0.78; 95% CI, 0.76-0.80), it was higher among younger survivors (SMR, 1.23-2.50, for those who died before 50) than the general population. Survivors had an elevated suicide rate (SMR, 1.28; 95% CI, 1.15-1.42), especially male (SMR, 1.35; 95% CI, 1.19-1.53) and stomach cancer survivors (SMR, 1.38; 95% CI, 1.14-1.66).Appropriate medical attention for long-term adult cancer survivors, especially younger survivors, is warranted to prevent premature deaths from non-cancer causes.

This paper proposes a novel mathematical model and scheduling system for real pharmaceutical industries (PI). To consider general characteristics of the PI, the proposed model employed a strategy to address a mixed integer linear programming (MILP) formulation. Heuristic techniques were then developed to solve complex scheduling problems for PI such as critical and bottleneck operations. These techniques are also helpful to reduce calculation time. The objective function of the proposed model is to minimize the total operation time (makespan) which is subject to the mass balance constraints and process boundary conditions. An illustrative case study is presented to demonstrate the features and capabilities of the proposed scheduling system.

Necrotizing enterocolitis (NEC) is a major gastrointestinal disorder in premature infants associated with high morbidity and mortality rates. When NEC is clinically suspected, radiological and laboratory studies should be performed to confirm the diagnosis and to aid in the management of patients. As the clinical manifestations of NEC are usually nonspecific, diagnoses are often made using abdominal radiographic findings, such as pneumatosis intestinalis. Clinicians typically consider the presence of pneumatosis intestinalis on radiographs as the definite evidence of stage II NEC. Here, we report 3 cases of preterm infants who had radiographic findings of pneumatosis intestinalis but did not have any other associated laboratory and clinical evidence of NEC, except bloody stools. The infants’ systemic manifestations were mild or absent, and all of them completely recovered within 2–3 days, as demonstrated by the resolution of pneumatosis intestinalis on abdominal radiographs. The combination of hematochezia and intestinal pneumatosis in preterm infants strongly suggests the diagnosis of NEC. In our cases, there was no laboratory evidence of inflammation or platelet consumption, and the clinical course was benign without any sings of surgical abdomen. Additionally, our patients had barium-induced colitis or milk protein allergy, which are other possible causes of pneumatosis intestinalis. Because pneumatosis intestinalis can result from causes other than NEC, it is important to consider clinical, laboratory, and radiological findings to confirm the diagnosis of NEC.

In most cases, persistent left superior vena cava (PLSVC) is asymptomatic and discovered accidentally. This case involves a 43-year-old male who underwent an emergency cadaveric liver transplantation. Postoperatively, the left internal jugular vein was cannulated using a sono-guided Seldinger technique in the intensive care unit. But the chest X-ray showed that the catheter followed the left paramediastinal course instead of crossing midline to the right to enter the superior vena cava. In consideration of the patient's status, an intra-arterial or extra-vascular placement could be excluded. For a diagnosis, we performed a bed-side transthoracic echocardiography with an agitated saline micro-bubble test. When agitated saline was injected through the catheter, the coronary sinus was initially opacified, and then the right atrium followed. In conclusion, we were able to make a diagnosis of PLSVC by a bedside test without radiation exposure.

Overproduction of prostaglandin E2 (PGE2) has been reported to be implicated in carcinogenesis. The intracellular level of PGE2 is regulated not only by its biosynthesis, but also by its degradation process. The key enzyme responsible for the biological inactivation of PGE2 is NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). This enzyme catalyzes NAD+-linked oxidation of 15(S)-hydroxyl group of prostaglandins to 15-keto metabolites, thereby inactivating PGE2. In the present study, we have found that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the terminal products of cyclooxygenase-2 (COX-2), upregulates 15-PGDH expression at both protein and mRNA levels in human breast cancer (MDA-MB-231) cells. The catalytic activity of 15-PGDH was also increased by 15d-PGJ2 treatment. By using deletion constructs of 15-PGDH promoter, we found that Ets is the most essential determinant for 15-PGDH induction. Elk-1, one of Ets transcription factor family members, was phosphorylated by 15d-PGJ2 treatment as determined by Western blot and immunocytochemical analyses. siRNA knockdown of Elk-1 suppressed 15-PGDH expression, indicating that Elk-1 plays a key role in 15-PGDH induction. We also observed that a pharmacological inhibition of ERK1/2 with U0126 abrogated the 15-PGJ2-induced activation of Elk1 and expression of 15-PGDH. Like 15d-PGJ2, its non-electrophilic analog 9,10-dihydro-15d-PGJ2 induced 15-PGDH, suggesting that the α,β-unsaturated carbonyl group of 15d-PGJ2 is not essential for its upregulation of 15-PGDH induction. The induction of Elk-1-mediated 15-PGDH expression by 15d-PGJ2 may account, in part, for its anti-inflammatory and anti-carcinogenic properties of this cyclopentenone prostaglandin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1860. doi:10.1158/1538-7445.AM2011-1860

Purpose:This study was to identify the stages of change in smoking cessation behavior and factors associated with the stages of smoking cessation behavior according to the trans-theoretical model. Methods:The subjects were154 industrial workersworkingat H Industryin N City, ChonnamProvince who werecurrentlysmoking and hadsmokedinthe past. Datawereanalyzedbydescriptivestatistics, ANOVA, andDuncan's multiplecomparison test using SAS Version 10.0. Results: The subjects were distributed among the stages of change in smoking cessationbehavior: therewere 28subjects (18.2%) intheprecontemplationstage, 71 (46.1%) in the contempla- tion stage, 21 (13.6%) in thepreparation stage, 8 (5.2%) inthe action stage, and 26 (16.9%) in themaintenance stage. The amount of smoking per day, self-efficacy, andadvantages (pros) of smokingweresignificantly asso- ciated with the stageof change in smoking cessation behavior. Conclusion:This studysuggested that the stage of change insmokingcessation behavior of thesubject shouldbeidentifiedpriortotheapplicationof intervention programs, nursing intervention strategies should be considered to reduce the amount of smoking per day, and the disadvantages of smoking should be perceived.