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1.  Experience of Advance Directives in a Hospice Center 
Journal of Korean Medical Science  2015;30(2):151-154.
To protect patient autonomy when confronting death, the importance of advance directives (ADs) has recently became an issue and gradually accepted in Korea. However, in real practice, ADs were not completed by patients but their families in most cases. To analyze the current situation of performing ADs, we reviewed medical charts of 214 terminal cancer patients admitted to the hospice center from October 2012 to September 2013. Seventy-six (35.5%) patients completed ADs. All ADs were completed by patients themselves. The most common reason for not completing ADs was poor physical and/or mental condition. As a proxy, the majority of patients preferred their spouses (55.3%). Few patients wanted life sustaining treatment (1.3%), however palliative sedation was accepted in 89.5%. The median timing of ADs after admission was three (0-90) days, and duration of survival since ADs was 22 (1-340) days. In conclusion, approximately one third of terminal cancer patients completed ADs by themselves. Considering that patient's poor condition is the main reason for not completing ADs, earlier discussion regarding ADs is necessary to enhance patients' participation.
Graphical Abstract
doi:10.3346/jkms.2015.30.2.151
PMCID: PMC4310940  PMID: 25653485
Advance Directives; Hospice Care; Neoplasms
2.  Highly Efficient Electronic Sensitization of Non-oxidized Graphene Flakes on Controlled Pore-loaded WO3 Nanofibers for Selective Detection of H2S Molecules 
Scientific Reports  2015;5:8067.
Tailoring of semiconducting metal oxide nanostructures, which possess controlled pore size and concentration, is of great value to accurately detect various volatile organic compounds in exhaled breath, which act as potential biomarkers for many health conditions. In this work, we have developed a very simple and robust route for controlling both the size and distribution of spherical pores in electrospun WO3 nanofibers (NFs) via a sacrificial templating route using polystyrene colloids with different diameters (200 nm and 500 nm). A tentacle-like structure with randomly distributed pores on the surface of electrospun WO3 NFs were achieved, which exhibited improved surface area as well as porosity. Porous WO3 NFs with enhanced surface area exhibited high gas response (Rair/Rgas = 43.1 at 5 ppm) towards small and light H2S molecules. In contrast, porous WO3 NFs with maximized pore diameter showed a high response (Rair/Rgas = 2.8 at 5 ppm) towards large and heavy acetone molecules. Further enhanced sensing performance (Rair/Rgas = 65.6 at 5 ppm H2S) was achieved by functionalizing porous WO3 NFs with 0.1 wt% non-oxidized graphene (NOGR) flakes by forming a Schottky barrier (ΔΦ = 0.11) at the junction between the WO3 NFs (Φ = 4.56 eV) and NOGR flakes (Φ = 4.67 eV), which showed high potential for the diagnosis of halitosis.
doi:10.1038/srep08067
PMCID: PMC4308697  PMID: 25626399
3.  The efficacy of pre-warming on reducing intraprocedural hypothermia in endovascular coiling of cerebral aneurysms 
BMC Anesthesiology  2015;15(1):8.
Background
The anesthetic management of patients undergoing endovascular treatment of cerebral aneurysms in the interventional neuroradiology suite can be challenged by hypothermia because of low ambient temperature for operating and maintaining its equipments. We evaluated the efficacy of skin surface warming prior to induction of anesthesia to prevent the decrease in core temperature and reduce the incidence of hypothermia.
Methods
Seventy-two patients were randomized to pre-warmed and control group. The patients in pre-warmed group were warmed 30 minutes before induction with a forced-air warming blanket set at 38°C. Pre-induction tympanic temperature (Tpre) was measured using an infrared tympanic thermometer and core temperature was measured at the esophagus immediately after intubation (T0) and recorded at 20 minutes intervals (T20, T40, T60, T80, T100, and T120). The number of patients who became hypothermic at each time was recorded.
Results
Tpre in the control and pre-warmed group were 36.4 ± 0.4°C and 36.6 ± 0.3°C, whereas T0 were 36.5 ± 0.4°C and 36.6 ± 0.2°C. Core temperatures in the pre-warmed group were significantly higher than the control group at T20, T40, T60, T80, T100, and T120 (P < 0.001). Compared to T0, core temperatures at each time were significantly lower in both two groups (P = 0.007 at T20 in pre-warmed group, P < 0.001 at the other times in both groups). The incidence of hypothermia was significantly lower in the pre-warmed group than the control group from T20 to T120 (P = 0.002 at T20, P < 0.001 at the other times).
Conclusion
Pre-warming for 30 minutes at 38°C did not modify the trends of the temperature decrease seen in the INR suite. It just slightly elevated the beginning post intubation base temperature. The rate of decrease was similar from T20 to T120. However, pre-warming considerably reduced the risk of intraprocedural hypothermia.
Trial registration
Clinical Research Information Service (CRiS) Identifier: KCT0001320. Registered December 19th, 2014.
doi:10.1186/1471-2253-15-8
PMCID: PMC4322559  PMID: 25670919
Cerebral aneurysm; Hypothermia; Interventional neuroradiology; Pre-warming
4.  Neddylation and deneddylation in cardiac biology 
Neddylation is a post-translational protein modification that conjugates a ubiquitin-like protein NEDD8 to target proteins. Similar to ubiquitination, neddylation is mediated by a cascade of three NEDD8 specific enzymes, an E1 activating enzyme, an E2 conjugating enzyme and one of the several E3 ligases. Neddylation is countered by the action of deneddylases via a process termed deneddylation. By altering the substrate’s conformation, stability, subcellular localization or binding affinity to DNA or proteins, neddylation regulates diverse cellular processes including the ubiquitin-proteasome system-mediated protein degradation, protein transcription, cell signaling etc. Dysregulation of neddylation has been linked to cancer, neurodegenerative disorders, and more recently, cardiac disease. Here we comprehensively overview the biochemistry, the proteome and the biological function of neddylation. We also summarize the recent progress in revealing the physiological and pathological role of neddylation and deneddylation in the heart.
PMCID: PMC4299693  PMID: 25628956
Post-translational modification; NEDD8; neddylation; deneddylation; cardiac disease
5.  Low C24-OH and C22-OH sulfatides in human renal cell carcinoma 
Journal of Mass Spectrometry  2014;49(5):409-416.
Histopathologic diagnosis of renal cell carcinoma (RCC) may sometimes be difficult with small biopsy samples. We applied histology-directed matrix-assisted laser desorption/ionization mass spectrometry to RCC samples to evaluate whether and how lipid profiles are different between RCC and normal tissue. We evaluated 59 RCC samples and 24 adjacent normal tissue samples collected from patients who underwent surgery. Five peaks were significantly differently expressed (p < 10−7) between RCCs and adjacent normal tissue samples. C24-OH sulfatide (ST-OH {18:1/24:0}[M-H]−; m/z 906.7 in the negative ion mode) and C22-OH sulfatide (ST-OH {18:1/22:0}[M-H]−; m/z 878.6 in the negative ion mode) were most significantly underexpressed in RCC samples, compared with adjacent normal tissue samples. With 100 random training-to-test partitions within these samples, the median prediction accuracy (RCC vs. normal) ranged from 96.3% to 100% at p cutoff values for feature selection ranging from 0.001 to 10−7. Two oncocytoma samples were predicted as normal tissue by five lipids that were differentially expressed between RCC and normal tissue at p < 10−7. Clear-cell, papillary, and chromophobe RCCs were different in lipid profiles. Permutation p- values for 0.632+ bootstrap cross-validated misclassification rates were less than 0.05 for all the classifiers. Thus, lipid profiles differentiate RCC from normal tissue and may possibly classify the histology of RCC. © 2014 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.
doi:10.1002/jms.3358
PMCID: PMC4274961  PMID: 24809902
renal cell carcinoma; lipid; MALDI; mass spectrometry; sulfatide
6.  Astrocytes refine cortical connectivity at dendritic spines 
eLife  null;3:e04047.
During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.
DOI: http://dx.doi.org/10.7554/eLife.04047.001
eLife digest
The central nervous system—which is made up of the brain and spinal cord—processes information from all over the body. The information travels through cells called neurons, which connect to each other at junctions called synapses. A single neuron can receive information from many different places because it is covered with protrusions known as dendritic spines that enable it to form synapses with a variety of other neurons.
In recent years, it has become apparent that brain cells other than neurons can influence synapse formation. The most abundant cells in the central nervous system are star-shaped cells known as astrocytes, which secrete molecules that control the timing and extent of synapse formation. Many previous studies on synapses have used a type of neuron found in the eye—called retinal ganglion cells—because these cells can be purified and grown in the laboratory in the absence of astrocytes. Under these conditions, they form very few synapses. However, in the presence of astrocytes the retinal ganglion cells form many more synapses, which is thought to be due to a protein called hevin and several other proteins that are secreted by the astrocytes.
Risher et al. studied a region of the brain called the cerebral cortex in mice that were missing hevin. In the cortex of normal mice, the neurons generally form synapses with other neurons within the cortex, or with neurons from other parts of the brain that send long-distance projections into the cortex. The experiments revealed that fewer of these long-distance synapses formed in the cortex of the mice missing hevin compared to normal mice. When hevin was injected directly into the brains of the mice, more long-distance synapses were formed.
Using a technique called three-dimensional electron microscopy, Risher et al. examined the structure of the synapses. In mice missing hevin, the synapses were much smaller and the dendritic spines were thin and long, indicating that they were not fully grown. The images also show that in normal mice, the dendritic spines often have multiple synapses when the animal is young, but many are lost as the brain matures so that only a single synapse remains in each dendritic spine. However, multiple synapses persist in the dendritic spines of mice lacking hevin, which could lead to competition between short and long distance synapses and may contribute to neurological diseases.
These results indicate that astrocytes are crucial for controlling the formation of synapses in dendritic spines. In humans, defects in hevin have been implicated in autism, schizophrenia and other neurological conditions. Future studies will seek to determine the precise role of astrocytes in these conditions, which may help us to develop new therapies.
DOI: http://dx.doi.org/10.7554/eLife.04047.002
doi:10.7554/eLife.04047
PMCID: PMC4286724  PMID: 25517933
synaptogenesis; thalamocortical; dendritic spines; astrocytes; mouse
7.  Multi-layer electrode with nano-Li4Ti5O12 aggregates sandwiched between carbon nanotube and graphene networks for high power Li-ion batteries 
Scientific Reports  2014;4:7334.
Self-aggregated Li4Ti5O12 particles sandwiched between graphene nanosheets (GNSs) and single-walled carbon nanotubes (SWCNTs) network are reported as new hybrid electrodes for high power Li-ion batteries. The multi-layer electrodes are fabricated by sequential process comprising air-spray coating of GNSs layer and the following electrostatic spray (E-spray) coating of well-dispersed colloidal Li4Ti5O12 nanoparticles, and subsequent air-spray coating of SWCNTs layer once again. In multi-stacked electrodes of GNSs/nanoporous Li4Ti5O12 aggregates/SWCNTs networks, GNSs and SWCNTs serve as conducting bridges, effectively interweaving the nanoporous Li4Ti5O12 aggregates, and help achieve superior rate capability as well as improved mechanical stability of the composite electrode by holding Li4Ti5O12 tightly without a binder. The multi-stacked electrodes deliver a specific capacity that maintains an impressively high capacity of 100 mA h g−1 at a high rate of 100C even after 1000 cycles.
doi:10.1038/srep07334
PMCID: PMC4256711  PMID: 25476980
8.  Aralia cordata Inhibits Triacylglycerol Biosynthesis in HepG2 Cells 
Journal of Medicinal Food  2013;16(12):1108-1114.
Abstract
Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first committed step in triacylglycerol (TAG) and phospholipid biosynthesis, and has been considered as one of the drug targets for treating hepatic steatosis, insulin resistance, and other metabolic disorders. The aim of this study was to investigate the GPAT inhibitors from natural products and to evaluate their effects. The methanol extract of Aralia cordata roots showed a strong inhibitory effect on the human GPAT1 activity. A further bioactivity-guided approach led to the isolation of ent-pimara-8(14),15-dien-19-oic acid, (PA), one of the major compounds of A. cordata, which suppressed the GPAT1 activity with IC50 value of 60.5 μM. PA markedly reduced de novo lysophosphatidic acid synthesis through inhibition of GPAT activity and therefore significantly decreased synthesis of TAG in the HepG2 cells. These results suggest that PA as well as A. cordata root extract could be beneficial in controlling lipid metabolism.
doi:10.1089/jmf.2012.2636
PMCID: PMC3868379  PMID: 24283275
Aralia cordata; ent-pimara-8(14),15-dien-19-oic acid; glycerol-3-phosphate acyltransferase; lysophophatidic acid; triacylglycerol
9.  Minimally Invasive Surgery for Axillary Osmidrosis Using a Combination of Subcutaneous Tissue Removal and a 1,444-nm Nd:YAG Laser 
Annals of Dermatology  2014;26(6):755-757.
Many treatment modalities have been developed for axillary osmidrosis. It is well known that the surgical treatment has the best results. However, there is a high possibility of side effects. The 1,444-nm lipolysis laser has been recently introduced to remove the apocrine glands. So far, subdermal coagulation treatment with a 1,444-nm Nd:YAG laser may be the least invasive and most effective therapy for axillary osmidrosis. However, according to our previous experience, the recurrence rate was 20%~30%. This emphasizes the need for combination of surgical method and non-surgical method and we combined subcutaneous tissue removal and photothermocoagulation with a 1,444-nm Nd:YAG laser. Three patients for bilateral axillary osmidrosis were enrolled. After an incision of about one-third the length of the widest transverse diameter, the apocrine glands were separated from the skin. And then apocrine glands within the marked area were destroyed by irradiation with a 1,444-nm Nd:YAG laser thereafter. All patients exhibited no relapse of axillary osmidrosis and were satisfied with the treatment results. A combination of subcutaneous tissue removal and Interstitial laser photothermocoagulation with a 1,444-nm Nd:YAG laser could be an effective treatment for mild to moderate axillary osmidrosis.
doi:10.5021/ad.2014.26.6.755
PMCID: PMC4252676  PMID: 25473231
1,444-nm Nd:YAG laser; Axillary osmidrosis
10.  A Case of Spontaneous Bacterial Peritonitis with Bacteremia Caused by Shewanella algae 
Infection & Chemotherapy  2014;46(4):264-268.
Human infection caused by Shewanella algae is rare, which usually occurred after direct contact with seawater or ingestion of raw seafood in the immunocompromised host. There have been anecdotal reports about Shewanella infections in human, but their pathogenic role and microbiologic data are limited. Here, we report a fatal case of spontaneous bacterial peritonitis with bacteremia due to S. algae in a 57-year-old male with liver cirrhosis who had no history of exposure to seawater or raw seafood. Polymicrobial infection with Streptococcus mitis and Escherichia coli was combined and the patient died in spite of early appropriate antimicrobial therapy and early goal-directed therapy for sepsis.
doi:10.3947/ic.2014.46.4.264
PMCID: PMC4285008  PMID: 25566408
Bacteremia; Liver Cirrhosis; Peritonitis; Polymicrobial infection; Shewanella algae
11.  Anatomic Feasibility of Posterior Cervical Pedicle Screw Placement in Children: Computerized Tomographic Analysis of Children Under 10 Years Old 
Objective
To evaluate the anatomical feasibility of 3.5 mm screw into the cervical spine in the pediatric population and to establish useful guidelines for their placement.
Methods
A total of 37 cervical spine computerized tomography scans (24 boys and 13 girls) were included in this study. All patients were younger than 10 years of age at the time of evaluation for the period of 2007-2011.
Results
For the C1 screw placement, entry point height (EPH) was the most restrictive factor (47.3% patients were larger than 3.5 mm). All C2 lamina had a height larger than 3.5 mm and 68.8% (51/74) of C2 lamina had a width thicker than 3.5 mm. For C2 pedicle width, 55.4% (41/74) of cases were larger than 3.5 mm, while 58.1% (43/74) of pedicle heights were larger than 3.5 mm. For pedicle width of subaxial spine, 75.7% (C3), 73% (C4), 82.4% (C5), 89.2% (C6), and 98.1% (C7, 1/54) were greater than 3.5 mm. Mean lamina width of subaxial cervical spine was 3.1 (C3), 2.7 (C4), 2.9 (C5), 3.8 (C6), and 4.0 mm (C7), respectively. Only 34.6% (127/370) of subaxial (C3-7) lamina thickness were greater than 3.5 mm. Mean length of lateral mass for the lateral mass screw placement was 9.28 (C3), 9.08 (C4), 8.81 (C5), 8.98 (C6), and 10.38 mm (C7).
Conclusion
C1 lateral mass fixation could be limited by the morphometrics of lateral mass height. C2 trans-lamina approach is preferable to C2 pedicle screw fixation. In subaxial spines, pedicle screw placement was preferable to trans-lamina screw placement, except at C7.
doi:10.3340/jkns.2014.56.6.475
PMCID: PMC4303722  PMID: 25628806
Anatomical morphometrics; Cervical spine; Pediatric population; Screw placement
12.  CK2α, over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells 
Background
The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation.
Methods
Protein and mRNA levels of CK2α and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay.
Results
In this study, we show that CK2α is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2α and Gli1 were broadly elevated and correlated (n = 52, r = 0.401, P < 0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2α and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2α and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n = 82, r = 0.554, P < 0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2α was silenced in two mesothelioma cell lines (H28 and H2052). CK2α siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2α inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2α resulted in an increase in Gli1 transcriptional activity in H28 cells.
Conclusions
Thus, we report for the first time that over-expressed CK2α positively regulate Hh/Gli1 signaling in human mesothelioma.
Electronic supplementary material
The online version of this article (doi:10.1186/s13046-014-0093-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s13046-014-0093-6
PMCID: PMC4254219  PMID: 25422081
CK2α; Hedgehog; Gli1; IHC; Mesothelioma
13.  Prognosis Prediction of Measurable Enhancing Lesion after Completion of Standard Concomitant Chemoradiotherapy and Adjuvant Temozolomide in Glioblastoma Patients: Application of Dynamic Susceptibility Contrast Perfusion and Diffusion-Weighted Imaging 
PLoS ONE  2014;9(11):e113587.
Purpose
To assess the prognosis predictability of a measurable enhancing lesion using histogram parameters produced by the normalized cerebral blood volume (nCBV) and normalized apparent diffusion coefficient (nADC) after completion of standard concomitant chemoradiotherapy (CCRT) and adjuvant temozolomide (TMZ) medication in glioblastoma multiforme (GBM) patients.
Materials and Methods
This study was approved by the institutional review board (IRB), and the requirement for informed consent was waived. A total of 59 patients with newly diagnosed GBM who received standard CCRT with TMZ and adjuvant TMZ for six cycles underwent perfusion-weighted and diffusion-weighted imaging. Twenty-seven patients had a measurable enhancing lesion and 32 patients lacked a measurable enhancing lesion based on the Response Assessment in Neuro-Oncology (RANO) criteria in the follow-up MRI, which was performed within 3 months after adjuvant TMZ therapy was completed. We measured the nCBV and nADC histogram parameters based on the measurable enhancing lesion. The progression free survival (PFS) was analyzed by the Kaplan-Meier method with the use of the log-rank test.
Results
The median PFS of patients lacking measurable enhancing lesion was longer than for those with measurable enhancing lesions (17.6 vs 3.3 months, P<.0001). There was a significant, positive correlation between the 99th percentile nCBV value of a measurable enhancing lesion and the PFS (P = .044, R2 = .152). In addition, the median PFS was longer in patients with a 99th percentile nCBV value ≧4.5 than it was in those with a value <4.5 (4.4 vs 3.1 months, P = .036).
Conclusion
We found that the nCBV value can be used for the prognosis prediction of a measurable enhancing lesion after the completion of standard treatment for GBM, wherein a high 99th percentile nCBV value (≧4.5) suggests a better PFS for GBM patients.
doi:10.1371/journal.pone.0113587
PMCID: PMC4242641  PMID: 25419975
14.  Thymosin Beta 4 Protects Mice from Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy 
PLoS ONE  2014;9(11):e110598.
Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.
doi:10.1371/journal.pone.0110598
PMCID: PMC4239012  PMID: 25412097
15.  Effect of Packaging Method and Storage Time on Physicochemical Characteristics of Dry-Cured Pork Neck Products at 10°C 
Dry-cured pork neck samples were stored at 10°C for 90 days under vacuum packaging (VP) or modified atmosphere packaging (MAP; 25% CO2+75% N2) conditions. The pH, moisture, water activity, total aerobic bacteria, and Enterobacteriaceae counts of dry-cured pork neck products with MAP were significantly lower than those with VP (p<0.05) after 90 days of storage. However, CIE b* and 2-thiobarbituric acid reacted substance (TBARS) values of the pork product with MAP were significantly higher (p<0.05) than those with VP. Total aerobic bacterial counts and Enterobacteriaceae counts of samples with MAP were lower than those with VP after 30 days of storage. Sensory results indicated that aroma, flavor and tenderness scores of the samples with both VP and MAP decreased during storage and the scores after >60 days of storage were lower than those at Day 1. In conclusion, despite presenting higher lipid oxidation, the samples stored in packages containing 25% CO2 for 90 days at 10°C have lower bacterial counts than vacuum-packed samples. Therefore, further studies should be performed on the packaging of dry-cured meat at adjusted concentrations of CO2.
doi:10.5713/ajas.2013.13728
PMCID: PMC4213708  PMID: 25358323
Color; Dry-Cured Pork Neck; Modified Atmosphere Packaging; Sensory Analysis; Thiobarbituric Acid Reacted Substance
16.  Infrared Fluorescent Protein 1.4 Genetic Labeling Tracks Engrafted Cardiac Progenitor Cells in Mouse Ischemic Hearts 
PLoS ONE  2014;9(10):e107841.
Stem cell therapy has a potential for regenerating damaged myocardium. However, a key obstacle to cell therapy’s success is the loss of engrafted cells due to apoptosis or necrosis in the ischemic myocardium. While many strategies have been developed to improve engrafted cell survival, tools to evaluate cell efficacy within the body are limited. Traditional genetic labeling tools, such as GFP-like fluorescent proteins (eGFP, DsRed, mCherry), have limited penetration depths in vivo due to tissue scattering and absorption. To circumvent these limitations, a near-infrared fluorescent mutant of the DrBphP bacteriophytochrome from Deinococcus radiodurans, IFP1.4, was developed for in vivo imaging, but it has yet to be used for in vivo stem/progenitor cell tracking. In this study, we incorporated IFP1.4 into mouse cardiac progenitor cells (CPCs) by a lentiviral vector. Live IFP1.4-labeled CPCs were imaged by their near-infrared fluorescence (NIRF) using an Odyssey scanner following overnight incubation with biliverdin. A significant linear correlation was observed between the amount of cells and NIRF signal intensity in in vitro studies. Lentiviral mediated IFP1.4 gene labeling is stable, and does not impact the apoptosis and cardiac differentiation of CPC. To assess efficacy of our model for engrafted cells in vivo, IFP1.4-labeled CPCs were intramyocardially injected into infarcted hearts. NIRF signals were collected at 1-day, 7-days, and 14-days post-injection using the Kodak in vivo multispectral imaging system. Strong NIRF signals from engrafted cells were imaged 1 day after injection. At 1 week after injection, 70% of the NIRF signal was lost when compared to the intensity of the day 1 signal. The data collected 2 weeks following transplantation showed an 88% decrease when compared to day 1. Our studies have shown that IFP1.4 gene labeling can be used to track the viability of transplanted cells in vivo.
doi:10.1371/journal.pone.0107841
PMCID: PMC4214633  PMID: 25357000
17.  Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth 
Oncogene  2013;33(16):2087-2097.
Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anti-cancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study we identified an interaction between Gli proteins and a transcription co-activator TAF9, and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and down-regulate Gli/TAF9 dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, a key control point of multiple oncogenic pathways, may be an effective anti-cancer strategy.
doi:10.1038/onc.2013.164
PMCID: PMC3947751  PMID: 23686308
Cancer; Targeted therapy; Gli; TAF9; Hedgehog pathway
18.  Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals 
Nutrition & Metabolism  2014;11(1):49.
Context
Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population. Objective: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m2) individuals.
Methods
We utilized a dual tracer technique (i.e., [6,6-2H2] glucose primed constant infusion and 1-[13C] glucose oral ingestion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios.
Results
Post-absorptive plasma glucose and insulin concentrations were not different between the three trials. Similarly, the response of glucose and insulin concentrations during the oral glucose tolerance tests (OGTT) was similar in the three trials. The results of the Matsuda index (ISI/M) were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2 ± 0.1, 1.1 ± 0.1, 1.3 ± 0.1 mg•kg-1•min-1), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2 ± 0.1, 4.3 ± 0.2, and 4.5 ± 0.4 mg•kg-1•min-1), respectively.
Conclusions
Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. However, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.
Electronic supplementary material
The online version of this article (doi:10.1186/1743-7075-11-49) contains supplementary material, which is available to authorized users.
doi:10.1186/1743-7075-11-49
PMCID: PMC4198625  PMID: 25324894
Insulin resistance; Liver; Muscle
19.  Keloids and Hypertrophic Scars: Characteristic Vascular Structures Visualized by Using Dermoscopy 
Annals of Dermatology  2014;26(5):603-609.
Background
Keloids and hypertrophic scars represent excessive scarring. They require different therapeutic approaches, which can be hampered because of an apparent lack of morphologic difference between the two diseases.
Objective
This study investigated the clinical and dermoscopic features of keloids and hypertrophic scars in order to help dermatologists distinguish these lesions better.
Methods
A total of 41 keloids and hypertrophic scars in 41 patients were examined clinically and by performing dermoscopy with a digital imaging system. Lesions were evaluated for vascular structures.
Results
Dermoscopy revealed vascular structures in most keloid lesions (90%) but in only 27% of hypertrophic scar lesions. The most common dermoscopic vascular structures in keloids were arborizing (52%), followed by linear irregular (33%) and commashaped (15%); these features were present but less evident in hypertrophic scars (9% for all types). The distribution frequency of the vascular structures differed significantly between diseases (p<0.001).
Conclusion
A strong association of vascular structures with keloids was observed on dermoscopic examination. The results suggest dermoscopic examination of vascular structures is a clinically useful diagnostic tool for differentiating between keloids and hypertrophic scars.
doi:10.5021/ad.2014.26.5.603
PMCID: PMC4198588  PMID: 25324653
Blood vessels; Dermoscopy; Hypertrophic scar (hypertrophic cicatrix); Keloid
20.  Epidermotropic Metastatic Melanoma Clinically Resembling Agminated Spitz Nevi 
Annals of Dermatology  2014;26(5):628-631.
Herein, we report a 36-year-old Asian male patient who presented with grouped multiple erythematous waxy papules and nodules on his right medial thigh. He had undergone amputation of the right second toe because of a stage IIa malignant melanoma, 3 years previously. At the time of surgery for the primary tumor, right inguinal lymph node dissection revealed no nodal involvement. Three years after the diagnosis of the primary tumor, crops of multiple erythematous papules and nodules developed. Initial histopathologic evaluation of the papules showed nests of small epithelioid cells similar to compound nevi. However, cytologic features, including high mitotic figures, lack of maturation, and some hyperchromatic nuclei suggested metastatic melanoma. In addition to the pathologic findings, the tumors were on the right thigh, which was the same side as the primary malignant melanoma. The patient underwent wide excision of the tumor and split-thickness skin grafting.
doi:10.5021/ad.2014.26.5.628
PMCID: PMC4198593  PMID: 25324658
Epidermotropic metastatic malignant melanoma
21.  Pancreatic adenocarcinosarcoma of monoclonal origin: A case report 
World Journal of Gastroenterology : WJG  2014;20(35):12682-12686.
Adenocarcinosarcoma, a neoplasm containing both carcinomatous and sarcomatous components, is a rare form of a cancer and the pathophysiology is currently poorly understood. Moreover, definitive treatment guidelines for this disease have not yet been established. Pancreatic adenocarcinosarcoma is even more rare and the prognosis is fatal. Here, we report a case of a 77-year-old male with pancreatic adenocarcinosarcoma and metastasis to the liver. The patient presented at our hospital with uncontrolled glucose levels and diabetes mellitus. The patient’s laboratory findings were unremarkable with the exception of elevated carbohydrate antigen 19-9 levels. Biopsies of the tumors in the pancreas and the liver revealed two types of tumors: pancreatic adenocarcinoma and a poorly differentiated sarcoma. To determine if KRAS mutations were present, we performed a peptide nucleic acid (PNA) clamp PCR-based assay. DNA sequencing by PNA clamp PCR identified a point mutation in codon 12 of exon 2 within KRAS from both tumor types. Because the KRAS mutation is observed in both tumor components, our findings support a monoclonal tumor origin followed by subsequent divergent differentiation into the sarcomatous and carcinomatous tumor populations. After we considered the patient’s status and the late stage of tumor detection, gemcitabine chemotherapy was administered.
doi:10.3748/wjg.v20.i35.12682
PMCID: PMC4168109  PMID: 25253976
Pancreas; Adenocarcinosarcoma; Metastasis; KRAS; DNA sequencing
22.  Real-Time Discrimination between Proliferation and Neuronal and Astroglial Differentiation of Human Neural Stem Cells 
Scientific Reports  2014;4:6319.
Neural stem cells (NSCs) are characterized by a capacity for self-renewal, differentiation into multiple neural lineages, all of which are considered to be promising components for neural regeneration. However, for cell-replacement therapies, it is essential to monitor the process of in vitro NSC differentiation and identify differentiated cell phenotypes. We report a real-time and label-free method that uses a capacitance sensor array to monitor the differentiation of human fetal brain-derived NSCs (hNSCs) and to identify the fates of differentiated cells. When hNSCs were placed under proliferation or differentiation conditions in five media, proliferating and differentiating hNSCs exhibited different frequency and time dependences of capacitance, indicating that the proliferation and differentiation status of hNSCs may be discriminated in real-time using our capacitance sensor. In addition, comparison between real-time capacitance and time-lapse optical images revealed that neuronal and astroglial differentiation of hNSCs may be identified in real-time without cell labeling.
doi:10.1038/srep06319
PMCID: PMC4159634  PMID: 25204726
23.  Dosimetric comparison of 4 MeV and 6 MeV electron beams for total skin irradiation 
Background
In this study, dosimetric aspects of TSEI consisting of a 4 MeV beam with no spoiler were investigated in comparison to a nominal 6 MeV beam with spoiler, and the potential for clinical applications was evaluated.
Methods
The TSEI technique is based on the Stanford technique, which utilizes a beam configuration of six-dual fields. MOSFETs were used to measure the optimal gantry angle, profile uniformity, and absolute dose at the calibration point. The depth dose curve of the central axis was measured in the treatment plane using EBT2 film. Photon contamination was measured as the dose at 5 cm depth in a solid water phantom relative to the maximum dose using a parallel plate ion chamber. A MOSFET dosimeter placed on the surface of a humanoid phantom, and EBT2 films inserted into a humanoid phantom were used to verify the TSEI commissioning.
Results
Dosimetric aspects of the 4 MeV TSEI beam, such as profile uniformity (±10%) and relative photon contamination (<0.001%), were comparable to those of a 6 MeV TSEI beam. The relative depth dose of the 4 MeV electrons was 81.4% at the surface and 100% at 0.4 cm. For the 6 MeV electrons, the relative depth dose was 93.4% at the surface and 100% from 0.2 cm to 0.4 cm. The calculated B-factor of the 4 MeV TSEI beam was 1.55, and 1.53 for the 6 MeV TSEI. 80% of the prescribed dose was obtained at 0.22 cm depth for the 4 MeV TSEI beam and 0.53 cm for the 6 MeV TSEI beam in the humanoid phantom measurement.
Conclusions
The suggested 4 MeV beam for TSEI could be applied to shallow depth skin diseases and to electron boost as second treatment course.
doi:10.1186/1748-717X-9-197
PMCID: PMC4261910  PMID: 25194217
Total skin electron irradiation (TSEI); Electron energy; Stanford Technique; Mycosis fungoides
24.  Epitaxial Relationships between Calcium Carbonate and Inorganic Substrates 
The polymorph-selective crystallization of calcium carbonate has been studied in terms of epitaxial relationship between the inorganic substrates and the aragonite/calcite polymorphs with implication in bioinspired mineralization. EpiCalc software was employed to assess the previously published experimental results on two different groups of inorganic substrates: aragonitic carbonate crystals (SrCO3, PbCO3, and BaCO3) and a hexagonal crystal family (α-Al2O3, α-SiO2, and LiNbO3). The maximum size of the overlayer (aragonite or calcite) was calculated for each substrate based on a threshold value of the dimensionless potential to estimate the relative nucleation preference of the polymorphs of calcium carbonate. The results were in good agreement with previous experimental observations, although stereochemical effects between the overlayer and substrate should be separately considered when existed. In assessing the polymorph-selective nucleation, the current method appeared to provide a better tool than the oversimplified mismatch parameters without invoking time-consuming molecular simulation\.
doi:10.3390/ijms150916320
PMCID: PMC4200811  PMID: 25226539
biomineralization; polymorphism; calcium carbonate; heterogeneous nucleation; epitaxy
25.  Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy 
PLoS ONE  2014;9(8):e104092.
Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed.
doi:10.1371/journal.pone.0104092
PMCID: PMC4126719  PMID: 25105891

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