Restricted VAR Hedging with the Presence of Multiple Breaks

Distinct from the existing literatures that most of them focussed on the case of a single change on issues related to structural change. This study addresses the practical advantage of hedging ratio when time varying structural breakings are considered. Data used in this study include daily observations of spot prices of WTI (Cushing, Oklahoma FOB), U.S. crude oil production, and futures closing prices of NYMEX over the period of 2002/1/2 ~ 2005/7/26. We compare on out-of-sample hedging effectiveness of this structural break with restricted VAR hedging model against standard VAR hedge model. It has been found that there are four structural breaks. And the improvement in hedging performance is clearly presented. Smaller hedging of a futures position can therefore reduce the investors cost extensively

Percutaneous transhepatic techniques for retrieving fractured and intrahepatically dislodged percutaneous transhepatic biliary drainage catheters

Dislodged intrabiliary drainage devices, including catheters, endoprostheses, and stents, may further impair drainage and cause various local reactions, vascular and gastrointestinal tract complications. Endoscopic approaches for management of plastic biliary endoprostheses have been extensively discussed. However, in rare cases of fracture of percutaneous transhepatic biliary drainage (PTBD) catheters, only a percutaneous transhepatic technique for retrieving should be applied to avoid further damage by its rigid fragment. We present the adjusted techniques using either a goose neck snare, over-the-wire balloon catheter, or biopsy forceps with image demonstration and reviews. We encountered two patients with PTBD tube fracture and intrahepatic dislodgment. In both patients, percutaneous approaches were used for successfully retrieving and removing the fractured catheter through transhepatic tract: one with the use of a biopsy forceps, another with an inflatable balloon catheter

Progesterone Increases Apoptosis and Inversely Decreases Autophagy in Human Hepatoma HA22T/VGH Cells Treated with Epirubicin

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. Epirubicin can induce intracellular reactive oxygen species and is widely used to treat unresectable HCC. Progesterone has been found to inhibit the proliferation of hepatoma cells. This study was designed to test the combined effects of epirubicin and progesterone on human hepatoma cell line, HA22T/VGH. These cells were treated with different concentrations of epirubicin with or without the coaddition of 30 μM progesterone and then analyzed for apoptosis, autophagy, and expressions of apoptotic-related proteins and multidrug-resistant gene. Epirubicin treatment dose-dependently inhibited the growth of HA22T/VGH cells. Addition of 30 μM progesterone, which was inactive alone, augmented the effect of epirubicin on the inhibition of growth of HA22T/VGH cells. Cotreatment with progesterone enhanced epirubicin-induced apoptosis, as evidenced by greater increase in caspase-3 activity and in the ratio of the apoptosis-regulating protein, Bax/Bcl-XL. The combination also caused a decrease in autophagy and in the expression of multidrug resistance-related protein 1 mRNA compared to epirubicin alone. This study shows the epirubicin/progesterone combination was more effective in increasing apoptosis and inversely decreasing autophagy on HA22T/VGH cells treated with epirubicin alone, suggesting that this combination can potentially be used to treat HCC

Isolation, Culture and Characterization of Hirsutella sinensis Mycelium from Caterpillar Fungus Fruiting Body

The caterpillar fungus Ophiocordyceps sinensis (previously called Cordyceps sinensis) has been used for centuries in Asia as a tonic to improve health and longevity. Recent studies show that O. sinensis produces a wide range of biological effects on cells, laboratory animals and humans, including anti-fatigue, anti-infection, anti-inflammatory, antioxidant, and anti-tumor activities. In view of the rarity of O. sinensis fruiting bodies in nature, cultivation of its anamorph mycelium represents a useful alternative for large-scale production. However, O. sinensis fruiting bodies harvested in nature harbor several fungal contaminants, a phenomenon that led to the isolation and characterization of a large number of incorrect mycelium strains. We report here the isolation of a mycelium from a fruiting body of O. sinensis and we identify the isolate as O. sinensis’ anamorph (also called Hirsutella sinensis) based on multi-locus sequence typing of several fungal genes (ITS, nrSSU, nrLSU, RPB1, RPB2, MCM7, β-tubulin, TEF-1α, and ATP6). The main characteristics of the isolated mycelium, including its optimal growth at low temperature (16°C) and its biochemical composition, are similar to that of O. sinensis fruiting bodies, indicating that the mycelium strain characterized here may be used as a substitute for the rare and expensive O. sinensis fruiting bodies found in nature

Risk factors for poor outcomes of children with acute acalculous cholecystitis

BACKGROUND: Acute acalculous cholecystitis (AAC) is generally considered to be a mild disease in children; however, if left untreated or treated without caution, AAC can lead to severe outcomes, such as death. The objectives of this study were to present the clinical features and identify the predictors of mortality in pediatric AAC. METHODS: Patients diagnosed with AAC between 2005 and 2012 were enrolled. AAC was defined by the presence of fever and an echo-proven thickened gallbladder wall exceeding 4 mm. A poor health outcome was defined as death. Further information related to the demographics, clinical manifestations, laboratory results, ultrasound findings, and pathogens present in the AAC patients was also collected. Predictors of mortality were identified by association analyses and confirmed by multivariate logistic regression. RESULTS: A total of 147 pediatric AAC patients (male/female = 1.01, mean age = 5.2 years) were included in this retrospective study. The most common clinical presentation was an elevated C-reactive protein level (84%) followed by hepatomegaly (80%) and anorexia (78%). AAC in children was associated with various diseases, including infectious diseases (70%), systemic diseases (13%), and malignancy (11%). Fourteen of the 147 (9.25%) patients died during the study period. The presences of thrombocytopenia, anemia, gallbladder sludge, hepatitis, and/or sepsis plus hepatitis were found to be the important predictors of AAC mortality. CONCLUSIONS: The factors associated with AAC mortality were anemia, thrombocytopenia, gallbladder sludge, hepatitis, and sepsis plus hepatitis. These predictors are likely to help clinicians identify patients who are at a high risk of poor prognoses and make appropriate clinical decisions

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

<p>Abstract</p> <p>Background</p> <p>The crude extract of the fruit bearing plant, <it>Physalis peruviana </it>(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p> <p>Methods</p> <p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p> <p>Results</p> <p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<it>p </it>< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<it>p </it>< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC₅₀) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G₁accumulation and slight arrest at the G₂/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G₂/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p> <p>Conclusions</p> <p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p

Brain computerized tomography reading in suspected acute ischemic stroke patients: what are essentials for medical students?

Background Few systematic methods prioritize the image education in medical students (MS). We hope to develop a checklist of brain computerized tomography (CT) reading in patients with suspected acute ischemic stroke (AIS) for MS and primary care (PC) physicians. Methods Our pilot group generated the items indicating specific structures or signs for the checklist of brain CT reading in suspected AIS patients for MS and PC physicians. These items were used in a modified web-based Delphi process using the online software “SurveyMonkey”. In total 15 panelists including neurologists, neurosurgeons, neuroradiologists, and emergency department physicians participated in the modified Delphi process. Each panelist was encouraged to express feedback, agreement or disagreement on the inclusion of each item using a 9-point Likert scale. Items with median scores of 7–9 were included in our final checklist. Results Fifty-two items were initially provided for the first round of the Delphi process. Of these, 35 achieved general agreement of being an essential item for the MS and PC physicians. The other 17 of the 52 items in this round and another two added items suggested by the panelists were further rated in the next round. Finally, 38 items were included in the essential checklist items of brain CT reading in suspected AIS patients for MS and PC physicians. Conclusions We established a reference regarding the essential items of brain CT reading in suspected AIS patients. We hope this helps to minimize malpractice and a delayed diagnosis, and to improve competency-based medical education for MS and PC physicians

Differentiation of Schizophrenia Patients from Healthy Subjects by Mismatch Negativity and Neuropsychological Tests

BACKGROUND: Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN) deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects. METHODOLOGY/PRINCIPAL FINDINGS: 120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ) were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%). CONCLUSIONS/SIGNIFICANCE: MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility

The Molecular Mechanisms and Therapeutic Effects of Potential Agents in Melanoma and Psoriasis

黑色素細胞癌是所有皮膚癌中最惡性、最容易轉移，且致死率最高的皮膚癌類型。全球高度轉移性黑色素細胞癌的發生率越來越高，治療策略如那些聚集於高侵略性黑色素癌細胞下游β-catenin / MITF訊號傳遞路徑軸線的治療策略是迫切需要的。治療標的針對內質網壓力 (ER stress) 已知可以促進癌細胞死亡並抑制轉移性腫瘤的上皮細胞間質轉化（EMT）。本研究目的在於確認厚朴酚是否可以促進內質網壓力有關的細胞凋亡及調節轉移性黑色素細胞癌。使用高轉移性黑色素細胞癌異種移植小鼠之腹膜轉移模型及電腦斷層掃描影像來評估厚朴酚的治療效果。內質網壓力標記物Calpain-10，是一種新的蛋白水解切割酶。利用基因靜默(gene silencing) 技術抑制CHOP / GADD153所調節的細胞凋亡作用以確定β-catenin / MITF訊號傳遞路徑軸線在黑素癌細胞中所扮演的角色。研究結果發現厚朴酚經由活化內質網壓力及抑制上皮細胞間質轉化可有效地降低黑色素細胞癌腹膜腔轉移和器官轉移。利用基因減弱技術抑制Calpain-10基因或CHOP / GADD153基因的表現可抑制由厚朴酚誘發之訊號傳遞路徑軸線β-catenin / MITF蛋白分解並抑制ERSE (ER stress response element) 或TCF / LEF (T cell-specific transcription factor/Lymphoid enhancer-binding factor) 螢光素酶活性和β-catenin蛋白激酶活性之相關生物效應。這些研究發現顯示了厚朴酚可以經由調節Calpain-10和CHOP / GADD153而抑制β-catenin / MITF訊號傳遞路徑軸線，進而顯著地阻止高度轉移性黑色素細胞癌的進展。 乾癬是一種自體免疫慢性發炎的皮膚疾病，影響約2％-3% 的人口。對於患者造成重大的心理負擔以及影響其生活品質的程度，不亞於其他重大慢性疾病，如關節炎、糖尿病、高血壓等。不少患者從青壯年時就得開始面對乾癬，在無治癒的希望下，許多患者合併有憂鬱、焦慮、酒精濫用的現象，甚至有些患者有自殺念頭。最近研究發現aryl hydrocarbon receptor (AhR) 在乾癬的致病機轉中扮演很重要的角色，然而是否AhR agonists對乾癬有治療效果仍然是未知的，所以我們將已知的AhR agonists: Omeprazole (OMP)及Leflunomide (LEU)用於由Imiquimod (IMQ)所誘導類似乾癬皮膚發炎之小鼠模式來評估AhR agonists是否有療效，動物實驗結果顯示OMP 及LEU 可藉由減少表皮免疫細胞的浸潤及白细胞介素-17的表現，進而減少由IMQ所誘導類似乾癬之皮膚發炎。此外，OMP及LEU可以增強表皮細胞間的細胞緊密連接 (cell tight junction) 及細胞粘著（cell-cell adhesion），進而增強皮膚屏障(skin barrier) 之功能。此外，高光譜影像 (Hyperspectral imaging) 已經被廣泛的應用於各種民生與軍事的用途，包括農藥殘留檢驗、食品安全檢驗、翡翠寶石鑑定、藝術品鑑定、地表的監測、生態環境的變遷、地理資訊的蒐集等應用，最近已有硏究將高光譜影像應用於醫學領域，包括評估腫瘤的良性與惡性及評估缺血性組織的血液灌注狀況。所以我們將高光譜影像應用於評估乾癬的嚴重度，動物實驗結果顯示高光譜影像之水及膠原蛋白的訊號在IMQ所誘導類似乾癬發炎之老鼠皮膚會明顯減少，而在正常老鼠的皮膚則沒有變化。我們的硏究結果顯示高光譜影像是快速、準確且可信任的技術，可應用於臨床評估乾癬的嚴重度。目前治療乾癬傳統用藥包括acitretin、methotrexate及cyclosporine，然而這些藥物有肝毒性、腎毒性或骨髓抑制等副作用。目前已有生物製劑用於治療中、重度乾癬，雖然生物製劑的副作用比傳統乾癬用藥少，但是生物製劑價格比起傳統用藥昂貴許多，我們的硏究顯示OMP及LEU確實可明顯減少由IMQ所誘導類似乾癬之皮膚發炎，而OMP及LEU的價格低且無明顯副作用。我們深信該研究將打開更多的視野，暸解AhR agonists減緩由IMQ誘導類似乾癬皮膚發炎之機轉 ，進而可將Omeprazole及Leflunomide應用於臨床治療乾癬。There is increasing global incidence of highly metastatic melanoma and therapeutic strategies like those focusing on the downstream beta-catenin/MITF axis of invading melanoma cells are urgently needed. Targeting endoplasmic reticulum (ER) stress can promote cancer cell death and inhibit epithelial mesenchymal transition (EMT) in metastatic tumors. However, whether Honokiol could promote ER stress-dependent apoptosis and regulate metastatic melanoma is still unkown. We therefore used the highly metastatic melanoma xenograft mouse model and computed tomography imaging to assess the therapeutic efficacy of Honokiol for peritoneal metastasis. The ER stress marker, Calpain-10, delineated a novel proteolytic cleavage enzyme, while CHOP/GADD153-regulated apoptosis was used for gene silencing to determine the role of the β-catenin/MITF axis in melanoma cells. Our results showed that Honokiol effectively decreased peritoneal dissemination and organ metastasis via ER stress activation and EMT marker inhibition. Knockdown Calpain-10 or CHOP/GADD153 blocked all of the biological effects in Honokiol-induced β-catenin/MITF cleavage, ERSE or TCF/LEF luciferase activity, and β-catenin kinase activity. These experimental outcomes suggest that Honokiol can significantly thwart the progression of highly metastatic melanoma using the β-catenin/MITF axis via prompt Calpain-10 and CHOP/GADD153 regulated cascades. We also explored the molecular mechanisms and therapeutic effects of potential agents in psoriasis. Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by and influx of inflammatory cell that is associated with multiple coexisting conditions. The aryl hydrocarbon receptor (AhR) has become increasingly recognized for its role in the differentiation and activity of immune cell subsets; however, its role in regulating the activity of immune cells by pharmacological effect of a receptor agonist has not been described. Here we first establish and present of short-wave infrared (SWIR, defined here as ∼1000 to 2000 nm) spectroscopy and imaging techniques for biological tissue optical property characterization. We conducted and identify a novel spectroscopic instrument (GAIA) application of AhR-mediated signaling in imiquimod (IMQ)-induced psoriatic inflammation, a mouse model that shares feature with the human disease. We found that GAIA precisely evaluated psoriatic inflammation and consistent with pathological histology, which specially survey the water and collagen signals of tissue constituents but not lipids. Simultaneously, we also show that deficiency of AhR expression by knockout (AhRKO) mice is induced and aggravated in spectroscopic image, immune cells and cytokine IL-17. In contrast, activation of AhR with an AhR agonists, Leflunomide (LEU) and Omeprazole (OMP) efficiently attenuates immune activity and IL-17 of production. In vitro study, primary goldfish keratocytes (PFK) demonstrated that AhR is essential for keratinocyte barrier function by trans epithelial electrical resistance (TEER) measurement. Our studies introduce AhR as another regulator of immune cell activity in vivo, regulation of inflammatory responses and skin barrier function. We open the possibility for novel therapeutic strategies in chronic inflammatory disorders and identify AhR agonist may be a potential therapeutic target for psoriasis.摘要 i Abstract iii Table of Contents v List of Tables viii Lists of Figures ix List of Abbreviations xi Chapter 1. Exploiting Honokiol-induced ER stress CHOP activation inhibits the growth and metastasis of melanoma by suppressing the MITF and β-catenin pathway 1 1.1 Introduction 3 1.2 Materials and Methods 6 1.2.1 Melanoma cells and Cell culture 6 1.2.2 Mouse xenograft model of animal peritoneal dissemination 6 1.2.3 Positron emission tomography/computed tomography (PET/CT) 7 1.2.4 Western blot analysis and immuno-precipitation 8 1.2.5 Calpain activity 8 1.2.6 TOP/FOP luciferase reporter assay 8 1.2.7 Immuno-fluorescence confocal laser scanning microscopy 9 1.2.8 In vitro kinase activity 9 1.2.9 Colony-forming assay 9 1.2.10 Cell migration assay 10 1.2.11 Web-based correlation 10 1.2.12 Statistical analyses 10 1.3 Results 12 1.3.1 Honokiol blocked highly metastatic melanoma in vivo 12 1.3.2 Honokiol prompted ER stress and Calpain-10 activity and delayed EMT markers 12 1.3.3 Honokiol enhanced Calpain10 and MITF-m interaction and caused MITF-m cleavage 13 1.3.4 Honokiol-induced CHOP/GADD153 regulated β-catenin activation 14 1.3.5 Honokiol induced ER stress and reduced MITF, β-catenin, and CDK2 expressions in animal melanoma tissues 14 1.3.6 High expressions of MITF, β-catenin, and CDK2 decreased the overall survival probability 15 1.4 Discussion 16 Chapter 2. Amelioration of psoriasis skin inflammation by aryl hydrocarbon receptor activation 23 Abstract 24 2.1 Introduction 25 2.2 Materials and Methods 30 2.2.1 Mice and treatments 30 2.2.2 Fish keratinocyte primary 30 2.2.3 Reagents 30 2.2.4 Hyperspectral imaging (HSI) system 31 2.2.5 Immunohistochemistry 31 2.2.6 Immunofluorescence 32 2.2.7 Hydroxyproline assay 32 2.2.8 ATP/ADP Measurements 32 2.2.9 Measurement of trans epithelial electrical resistance (TEER) 33 2.2.10 Statistical Analyses 33 2.3 Results 34 2.3.1 IMQ-induced psoriasis-like skin inflammation with decreased hyperspectral imaging signals of water, collagen, and water combined with collagen, but not lipid 34 2.3.2 Exacerbated psoriasis-like skin inflammation in AhR-deficient mice 35 2.3.3 Pathogenic cytokine IL-17 and immune cells are significantly increased in the IMQ-induced psoriasis-like skin of AhR deficient mice. 37 2.3.4 AhR activation by LEU and OMP obviously attenuate IMQ-induced psoriasis-like skin inflammation 38 2.3.5 AhR activation by LEU and OMP efficiently decrease the immune activity and production of IL-17. 41 2.3.6 AhR activation by LEU and OMP enhances cell tight junction. 42 2.3.7 AhR activation by LEU and OMP enhances cell-cell adhesion. 43 2.4 Discussion 45 2.5 Future direction 53 Tables 54 Figures 58 Reference 8