bluuebunny/crossref_metadata_2025 huggingface dataset:
Nigella sativaand Its Protective Role in Oxidative Stress and Hypertension
Authors: Leong Xin-Fang , Rais Mustafa Mohd , Jaarin Kamsiah
Published: March 2013

Hypertension increases the risk for a variety of cardiovascular diseases, including stroke, coronary artery disease, heart failure, and peripheral vascular disease. The increase in oxidative stress has been associated with the pathogenesis of hypertension. Increase of blood pressure is due to an imbalance between antioxidants defence mechanisms and free radical productions. Excessive production of reactive oxygen species reduces nitric oxide bioavailability leading to an endothelial dysfunction and a subsequent increase in total peripheral resistance. Hypertension can cause few symptoms until it reaches the advanced stage and poses serious health problems with lifelong consequences. Hypertensive patients are required to take drugs for life to control the hypertension and prevent complications. Some of these drugs are expensive and may have adverse reactions. Hence, it is timely to examine scientifically, complimentary therapies that are more effective and with minimal undesirable effects.Nigella sativa(NS) and its active constituents have been documented to exhibit antioxidant, hypotensive, calcium channel blockade and diuretic properties which may contribute to reduce blood pressure. This suggests a potential role of NS in the management of hypertension, and thus more studies should be conducted to evaluate its effectiveness.
A Cross-Layer Security Scheme of Web-Services-Based Communications for IEEE 1451 Sensor and Actuator Networks
Authors: Wu Jun , Zhan Ming , Duan Bin , Liu Jiang
Published: March 2013

IEEE 1451 standard has been proposed to provide a common communication interface and transducer electric data sheet format for wired and wireless distributed applications in smart transducers (sensors and actuators). Currently, a unified Web service for IEEE 1451 smart transducers is a must. However, ensuring the security of web-services-based communications for IEEE 1451 smart transducers is an unsolved problem. In this paper, we proposed a cross-layer security mechanism that deals with the requirements of authentication, integrity, confidentiality, and availability across the communication process in IEEE 1451 smart transducers. The scheme contains three cross-layer components logically, including XML Encryption and Signature, SOAP Security Extension, and Web Services Description Language (WSDL) Security Checking. The former two components satisfy the requirements of confidentiality, availability, integrity, authentication, nonrepudiation, and freshness. The third component satisfies the requirement of availability, which can protect the system against denial-of-service (DoS) attack. The three cross-layer security components are integrated seamlessly in our scheme. To evaluate the overhead, we perform tests to evaluate the effect of message size on the performance of the access inquiry web service. The result supports the usefulness and feasibility of our scheme.
Analysis of DC Electrical Conductivity Models of Carbon Nanotube-Polymer Composites with Potential Application to Nanometric Electronic Devices
Authors: Vargas-Bernal Rafael , Herrera-Pérez Gabriel , Calixto-Olalde Ma. Elena , Tecpoyotl-Torres Margarita
Published: March 2013

The design of nanometric electronic devices requires novel materials for improving their electrical performance from stages of design until their fabrication. Until now, several DC electrical conductivity models for composite materials have been proposed. However, these models must be valued to identify main design parameters that more efficiently control the electrical properties of the materials to be developed. In this paper, four different models used for modeling DC electrical conductivity of carbon nanotube-polymer composites are studied with the aim of obtaining a complete list of design parameters that allow guarantying to the designer an increase in electrical properties of the composite by means of carbon nanotubes.
Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy
Authors: Taylor Allan W. , Mosimaneotsile Barudi , Mathebula Unami , Mathoma Anikie , Moathlodi Ritah , Theebetsile Irene , Samandari Taraz
Published: March 2013

Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not established in human-immunodeficiency-virus-(HIV-) infected women who experience pregnancy during the course of therapy.Design.Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review.Results. Among 196 pregnant women, 103 (52.6%) were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095) of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.).Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.
Numerical Simulation and Stability Study of Natural Convection in an Inclined Rectangular Cavity
Authors: Dou Hua-Shu , Jiang Gang , Lei Chengwang
Published: March 2013

This paper examines the process of instability of natural convection in an inclined cavity based on numerical simulations. The energy gradient method is employed to analyze the physics of the flow instability in natural convection. It is found that the maximum value of the energy gradient function in the flow field correlates well with the location where flow instability occurs. Meanwhile, the effects of the flow time, the plate length, and the inclination angle on the instability have also been discussed. It is observed that the locations of instabilities migrate right as the flow time increased. With the increase of plate length, the onset time of the instability on the top wall of the cavity decreases gradually and the locations of instabilities move to the right side. Furthermore, the locations of instability move left with the increase of the inclination angle in a certain range. However, these positions move right as the accumulation of the heat flux is restrained in the lower left corner of the cavity once the inclination angle exceeds a certain range.
Propolis Induces Chondroitin/Dermatan Sulphate and Hyaluronic Acid Accumulation in the Skin of Burned Wound
Authors: Olczyk Pawel , Komosinska-Vassev Katarzyna , Winsz-Szczotka Katarzyna , Stojko Jerzy , Klimek Katarzyna , Kozma Ewa M.
Published: March 2013

Changes in extracellular matrix glycosaminoglycans during the wound repair allowed us to apply the burn model in which therapeutic efficacy of propolis and silver sulfadiazine was compared. Burns were inflicted on four pigs. Glycosaminoglycans isolated from healthy and burned skin were quantified using a hexuronic acid assay, electrophoretic fractionation, and densitometric analyses. Using the reverse-phase HPLC the profile of sulfated disaccharides released by chondroitinase ABC from chondroitin/dermatan sulfates was estimated. Chondroitin/dermatan sulfates and hyaluronic acid were found in all samples. Propolis stimulated significant changes in the content of particular glycosaminoglycan types during burn healing. Glycosaminoglycans alterations after silver sulfadiazine application were less expressed. Propolis maintained high contribution of 4-O-sulfated disaccharides to chondroitin/dermatan sulfates structure and low level of 6-O-sulfated ones throughout the observed period of healing. Propolis led to preservation of significant contribution of disulfated disaccharides especially 2,4-O-disulfated ones to chondroitin sulfates/dermatan sulfates structure throughout the observed period of healing. Our findings demonstrate that propolis accelerates the burned tissue repair by stimulation of the wound bed glycosaminoglycan accumulation needed for granulation, tissue growth, and wound closure. Moreover, propolis accelerates chondroitin/dermatan sulfates structure modification responsible for binding growth factors playing the crucial role in the tissue repair.
A Reappraisal of Chemotherapy-Induced Liver Injury in Colorectal Liver Metastases before the Era of Antiangiogenics
Authors: Nguyen-Khac Eric , Lobry Céline , Chatelain Denis , Fuks David , Joly Jean Paul , Brevet Marie , Tramier Blaise , Mouly Charlotte , Hautefeuille Vincent , Chauffert Bruno , Regimbeau Jean Marc
Published: March 2013

Background and Aims.Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab.Methods.Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics.Results.Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, ), especially LV5FU2 (). SD was associated with oxaliplatin (54.5% versus 23.5%, ) and low body mass index (). NRH was associated with oxaliplatin () and extensive resection (). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF (), longer hospitalization in case of surgical hepatitis (), and greater blood loss in case of portal fibrosis ().Conclusions.Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality.
On the Expected Discounted Penalty Function for a Markov Regime-Switching Insurance Risk Model with Stochastic Premium Income
Authors: Yu Wenguang
Published: March 2013

We consider a Markovian regime-switching risk model (also called the Markov-modulated risk model) with stochastic premium income, in which the premium income and the claim occurrence are driven by the Markovian regime-switching process. The purpose of this paper is to study the integral equations satisfied by the expected discounted penalty function. In particular, the discount interest force process is also regulated by the Markovian regime-switching process. Applications of the integral equations are given to be the Laplace transform of the time of ruin, the deficit at ruin, and the surplus immediately before ruin occurs. For exponential distribution, the explicit expressions for these quantities are obtained. Finally, a numerical example is also given to illustrate the effect of the related parameters on these quantities.
Bonding, Structure, and Stability of [(Na) n(Phe) m] n+ Clusters: Some Surprising Results from an Experimental and Theoretical Investigation in Gas Phase
Authors: Caetano Melissa S. , Ramalho Teodorico C. , Vieira Tales G. , Gonçalves Arlan da Silva , Mancini Daiana T. , da Cunha Elaine F. F.
Published: March 2013

Structure and stability of clusters in the ground state were analyzed at the theoretical and experimental levels. Our experimental and theoretical findings showed that the clusters in gas phase tend to form mainly planar rings of four members. The symmetry and the small dipole moment in these specific configurations suggested that their stability could be associated with an alignment of the water molecules, maximizing attractive electrostatic interactions caused by changes in the charge distribution of the clusters.
Removal of Methylene Blue from Wastewater by Adsorption onto ZnCl2 Activated Corn Husk Carbon Equilibrium Studies
Authors: Khodaie Maryam , Ghasemi Nahid , Moradi Babak , Rahimi Mohsen
Published: March 2013

The removal of methylene blue by activated carbon of corn husk by ZnCl2 activation (CHACZ) was investigated in the present study. Adsorption studies were performed by batch experiments. The effect of pH, initial dye concentration, adsorbent dose, the particle size of CHACZ, agitation speed, temperature, and contact time was explored. The equilibrium adsorption data were analyzed using two widely applied isotherms: Langmuir, Freundlich. Best fits were found to be Freundlich isotherm. Langmuir adsorption capacity (Qm) in 298, 308, and 318 K is 462.96, 546.45, and 662.25 mgg−1. The amount of RL indicates that CHACZ has a favorable adsorption. Maximum MB removal was observed at pH 4.0. The results indicate that CHACZ is an efficient adsorbent for removing dye from wastewater.
Changes in Plasma Ghrelin and Serum Leptin Levels after Cisplatin-Based Transcatheter Arterial Infusion Chemotherapy for Hepatocellular Carcinoma
Authors: Matsumura Tomoaki , Arai Makoto , Yoshikawa Masaharu , Sudo Kentaro , Nakamura Kazuyoshi , Katsuno Tatsuro , Kanai Fumihiko , Yamaguchi Taketo , Yokosuka Osamu
Published: March 2013

Background and Objective. Cisplatin-based chemotherapy is widely recognized to cause severe gastrointestinal disorders like nausea, vomiting, and appetite loss. The aim of this study was to assess whether cisplatin-based transcatheter arterial infusion (TAI) chemotherapy reduces plasma ghrelin levels and food intake in hepatocellular carcinoma (HCC) patients. Methods. Seventeen patients with HCC who underwent cisplatin-based TAI chemotherapy (80–100 mg/body) were enrolled in this study. Changes in peptide hormones, including ghrelin and leptin, as well as cytokines, were measured before and after chemotherapy. Appetite was evaluated by visual analog scale (VAS) and food intake was scored by eleven stages (0–10). Results. Appetite and food intake were significantly decreased after chemotherapy (P<0.05). Plasma acylated ghrelin levels before therapy and at day 1, day 7, and day 14 after chemotherapy were 10.4 ± 7.2, 4.7 ± 4.7, 11.7 ± 8.9, and 9.3 ± 6.6 fmol/mL, respectively. The level on day 1 was decreased significantly (P<0.05). In contrast, the levels of leptin, granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) on day 1 were increased significantly (P<0.05). Conclusions. TAI for HCC reduced plasma acylated ghrelin levels, appetite, and food intake significantly. In addition, it increased serum leptin levels.
Synthesis of Polypyrrole Inverse Opal in [bmim]PF6- Containing Acetonitrile and the Application of the Inverse Opal in Cell Prototype
Authors: Yan Wei , Dong Qi-Qi , Sun Li-Ning , Deng Wei , Wu Shaoping
Published: March 2013

Most primary cells use Zn or Li as the anode, a metallic oxide as the cathode, and an acidic or alkaline solution or moist past as the electrolytic solution. In this paper, highly ordered polypyrrole (PPy) inverse opals have been successfully synthesized in the acetonitrile solution containing [bmim]PF6. PPy films were prepared under the same experimental conditions. Cyclic voltammograms of the PPy film and the PPy inverse opal in neutral phosphate buffer solution (PBS) were recorded. X‐ray photoelectron spectroscopy technique was used to investigate the structural surface of the PPy films and the PPy inverse opals. It is found that the anions kept dedoping from the PPy films during the potential scanning process, resulting in the electrochemical inactivity. Although anions also kept dedoping from the PPy inverse opals, the anions from PBS could dope into the inverse opal, explaining why the PPy inverse opals kept their electrochemical activity. An environmental friendly cell prototype was constructed, using the PPy inverse opal as the anode. The electrolytes in both the cathodic and anodic half‐cells were neutral PBSs. The open‐circuit potential of the cell prototype reached 0.487 V and showed a stable output over several hundred hours.
A Hybrid Cellular Automata Model of Multicellular Tumour Spheroid Growth in Hypoxic Microenvironment
Authors: Cai Yan , Wu Jie , Xu Shixiong , Li Zhiyong
Published: March 2013

A three-dimensional hybrid cellular automata (CA) model is developed to study the dynamic process of multicellular tumour spheroid (MTS) growth by introducing hypoxia as an important microenvironment factor which influences cell migration and cell phenotype expression. The model enables us to examine the effects of different hypoxic environments on the growth history of the MTS and to study the dynamic interactions between MTS growth and chemical environments. The results include the spatial distribution of different phenotypes of tumour cells and associated oxygen concentration distributions under hypoxic conditions. The discussion of the model system responses to the varied hypoxic conditions reveals that the improvement of the resistance of tumour cells to a hypoxic environment may be important in the tumour normalization therapy.
Investment and Economy Analysis of Water-Source Heat Pump System in Chongqing, China
Authors: Ding Yong , Huang Xin , Wu Xiaobo , Li Baizhan
Published: March 2013

In China, the application of renewable energy witnesses rapid development. In the near future, a lot of demonstration projects will be built and thus it is urgent to know the economics of renewable energy building application technologies. Based on the renewable energy demonstration projects in Chongqing city, the author discussed the economy issue of water-source heat pump system (WSHPs) in order to provide suggestions for the application projects. According to the design information of demonstration projects, the average incremental investment, allowance, and payback period are calculated in this paper. Comparing WSHPs with traditional heating, ventilation, and air conditioning (HVAC) system, the saved energy of WSHPs is estimated in the current paper. The author calculated the amount of saved energy in unit applied area and unit intake water. Besides, the economy and efficiency of WSHPs project is analyzed at the end of this paper.
Nuclear Control of the Inflammatory Response in Mammals by Peroxisome Proliferator-Activated Receptors
Authors: Mandard Stéphane , Patsouris David
Published: March 2013

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play pivotal roles in the regulation of a very large number of biological processes including inflammation. Using specific examples, this paper focuses on the interplay between PPARs and innate immunity/inflammation and, when possible, compares it among species. We focus on recent discoveries establishing how inflammation and PPARs interact in the context of obesity-induced inflammation and type 2 diabetes, mostly in mouse and humans. We illustrate that PPARγability to alleviate obesity-associated inflammation raises an interesting pharmacologic potential. In the light of recent findings, the protective role of PPARαand PPARβ/δagainst the hepatic inflammatory response is also addressed. While PPARs agonists are well-established agents that can treat numerous inflammatory issues in rodents and humans, surprisingly very little has been described in other species. We therefore also review the implication of PPARs in inflammatory bowel disease; acute-phase response; and central, cardiac, and endothelial inflammation and compare it along different species (mainly mouse, rat, human, and pig). In the light of the data available in the literature, there is no doubt that more studies concerning the impact of PPAR ligands in livestock should be undertaken because it may finally raise unconsidered health and sanitary benefits.
Cosmological Dynamics of a Hybrid Chameleon Scenario
Authors: Nozari Kourosh , Rashidi Narges
Published: March 2013

We consider a hybrid scalar field which is nonminimally coupled to the matter and models a chameleon cosmology. By introducing an effective potential, we study the dependence of the effective potential's minimum and hybrid chameleon field's masses on the local matter density. In a dynamical system technique, we analyze the phase space of this two-field chameleon model, find its fixed points and study their stability. We show that the hybrid chameleon domination solution is a stable attractor and the universe in this setup experiences a phantom divide crossing.
Late Recurrence of Benign Multicystic Peritoneal Mesothelioma Complicated with an Incisional Hernia
Authors: Canbay Emel , Ishibashi Haruaki , Sako Shouzou , Kitai Toshiyuki , Nishino Eisei , Yonemura Yutaka
Published: March 2013

Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease arising from the peritoneal mesothelium. Here, we report a 57-year-old woman admitted to our unit with an incisional hernia fifteen years later following her first operation due to BMPM. Computerized tomography demonstrated a cystic appearing mass with intraabdominal extension in hernia sac. The patient underwent en bloc resection of the mass and hernia repair. An immunohistochemical analysis of the mass confirmed the recurrence of BMPM. Our case supports that BMPM has slowly progressive nature and can recur with complicated incisional hernia long time after primary resection. Diagnosis and long-term followup are crucial for clarifying the characteristics of this disease.
MDCT in the Differentiation of Adrenal Masses: Comparison between Different Scan Delays for the Evaluation of Intralesional Washout
Authors: Angelelli Giuseppe , Mancini Maria Elisabetta , Moschetta Marco , Pedote Pasquale , Pignataro Pasquale , Scardapane Arnaldo
Published: March 2013

Purpose. To evaluate the accuracy of the washout in the differential diagnosis between adenomas and nonadenomas and to compare the obtained results in delayed CT scans at 5, 10 and 15 minutes. Methods. Fifty patients with adrenal masses were prospectively evaluated. CT scans were performed by using a 320‐row MDCT device, before and after injection of contrast material. In 25 cases, delayed scans were performed at 5′ and 10′ (group 1), while in the remaining 25, at 5′ and 15′ (group 2). Absolute and relative wash‐out percentage values (APW and RPW) were calculated. Results. Differential diagnosis between adenomas and nonadenomas was obtained in 48/50 (96%) cases, with sensitivity, specificity, and accuracy values of 96%, 95%, and 96%, respectively. In group 1, APW and RPW values were, respectively, 69.8% and 67.2% at 5′ and 75.9% and 73.5% at 10′ for adenomas and 25.1% and 15.8% at 5′ and 33.5% and 20.5% at 10′ for nonadenomas. In group 2, APW and RPW values were 63% and 54.6% at 5′ and 73.8% and 65.5% at 15′ for adenomas and 22% and 12.5% at 5′ and 35.5% and 19.9% at 15′ for nonadenomas. Conclusions. The evaluation of the wash‐out values in CT scans performed at 5′, 10′, and 15′ provides comparable diagnostic results. CT scans performed at 5′ are, therefore, to be preferred, since they reduce the examination time and patient discomfort.
Dormant Cancer Cells Contribute to Residual Disease in a Model of Reversible Pancreatic Cancer
Authors: Lin Wan-chi , Rajbhandari Nirakar , Liu Chengbao , Sakamoto Kazuhito , Zhang Qian , Triplett Aleata A. , Batra Surinder K. , Opavsky Rene , Felsher Dean W. , DiMaio Dominick J. , Hollingsworth Michael A. , Morris John P. , Hebrok Matthias , Witkiewicz Agnieszka K. , Brody Jonathan R. , Rui Hallgeir , Wagner Kay-Uwe
Published: March 2013

The initiation and progression of pancreatic ductal adenocarcinoma (PDAC) is governed by a series of genetic and epigenetic changes, but it is still unknown whether these alterations are required for the maintenance of primary and metastatic PDAC. We show here that the c-Myc oncogene is upregulated throughout the entire process of neoplastic progression in human PDAC and in genetically engineered mice that express mutant Kras. To experimentally address whether c-Myc is essential for the growth and survival of cancer cells, we developed a novel mouse model that allows a temporally and spatially controlled expression of this oncogene in pancreatic progenitors and derived lineages of the exocrine pancreas. Unlike previous reports, upregulation of c-Myc was sufficient to induce the formation of adenocarcinomas after a short latency without additional genetic manipulation of cell survival pathways. Deficiency in Cdkn2a increased the rate of metastasis but had no effect on tumor latency or c-Myc–mediated cancer maintenance. Despite a macroscopically complete regression of primary, metastatic, and transplantable tumors following the ablation of c-Myc, some cancer cells remained dormant. A significant number of these residual neoplastic cells expressed cancer stem cell markers, and re-expression of exogenous c-Myc in these cells led to rapid cancer recurrence. Collectively, the results of this study suggest that c-Myc plays a significant role in the progression and maintenance of PDAC, but besides targeting this oncogene or its downstream effectors, additional therapeutic strategies are necessary to eradicate residual cancer cells to prevent disease recurrence. Cancer Res; 73(6); 1821–30. ©2012 AACR.
Mammographic Breast Density Response to Aromatase Inhibition
Authors: Vachon Celine M. , Suman Vera J. , Brandt Kathleen R. , Kosel Matthew L. , Buzdar Aman U. , Olson Janet E. , Wu Fang-Fang , Flickinger Lynn M. , Ursin Giske , Elliott Catherine R. , Shepherd Lois , Weinshilboum Richard M. , Goss Paul E. , Ingle James N.
Published: March 2013

Purpose: Mammographic breast density (MBD) is decreased by tamoxifen, but the effect of aromatase inhibitors is less clear.

Experimental Design: We enrolled early-stage postmenopausal patients with breast cancer initiating adjuvant aromatase inhibitor therapy and ascertained mammograms before and at an average 10 months of aromatase inhibitor therapy. We matched cases to healthy postmenopausal women (controls) from a large mammography screening cohort on age, baseline body mass index, baseline MBD, and interval between mammograms. We estimated change in MBD using a computer-assisted thresholding program (Cumulus) and compared differences between cases and matched controls.

Results: In predominantly White women (96%), we found 14% of the 387 eligible cases had a MBD reduction of at least 5% after an average of 10 months of aromatase inhibitor therapy. MBD reductions were associated with higher baseline MBD, aromatase inhibitor use for more than 12 months, and prior postmenopausal hormone use. Comparing each case with her matched control, there was no evidence of an association of change in MBD with aromatase inhibitor therapy [median case–control difference among 369 pairs was −0.1% (10th and 90th percentile: −5.9%, 5.2%) P = 0.51]. Case–control differences were similar by type of aromatase inhibitor (P's 0.41 and 0.56); prior use of postmenopausal hormones (P = 0.85); baseline MBD (P = 0.55); and length of aromatase inhibitor therapy (P = 0.08).

Conclusions: In postmenopausal women treated with aromatase inhibitors, 14% of cases had a MBD reduction of more than 5%, but these decreases did not differ from matched controls. These data suggest that MBD is not a clinically useful biomarker for predicting the value of aromatase inhibitor therapy in White postmenopausal women. Clin Cancer Res; 19(8); 2144–53. ©2013 AACR.
Combining Hedgehog Signaling Inhibition with Focal Irradiation on Reduction of Pancreatic Cancer Metastasis
Authors: Gu Dongsheng , Liu Hailan , Su Gloria H. , Zhang Xiaoli , Chin-Sinex Helen , Hanenberg Helmut , Mendonca Marc S. , Shannon Harlan E. , Chiorean E. Gabriela , Xie Jingwu
Published: March 2013

Pancreatic cancer often presents in advanced stages and is unresponsive to conventional treatments. Thus, the need to develop novel treatment strategies for pancreatic cancer has never been greater. Here, we report that combination of focal irradiation with hedgehog (Hh) signaling inhibition exerts better than additive effects on reducing metastases. In an orthotopic model, we found that focal irradiation alone effectively reduced primary tumor growth but did not significantly affect metastasis. We hypothesized that cancer stem cells (CSC) of pancreatic cancer are responsible for the residual tumors following irradiation, which may be regulated by Hh signaling. To test our hypothesis, we showed that tumor metastasis in our model was accompanied by increased expression of CSC cell surface markers as well as Hh target genes. We generated tumor spheres from orthotopic pancreatic and metastatic tumors, which have elevated levels of CSC markers relative to the parental cells and elevated expression of Hh target genes. Irradiation of tumor spheres further elevated CSC cell surface markers and increased Hh target gene expression. Combination of Hh signaling inhibition with radiation had more than additive effects on tumor sphere regeneration in vitro. This phenotype was observed in two independent cell lines. In our orthotopic animal model, focal radiation plus Hh inhibition had more than additive effects on reducing lymph node metastasis. We identified several potential molecules in mediating Hh signaling effects. Taken together, our data provide a rationale for combined use of Hh inhibition with irradiation for clinical treatment of patients with pancreatic cancer. Mol Cancer Ther; 12(6); 1038–48. ©2013 AACR.
Curcumin-Targeting Pericellular Serine Protease Matriptase Role in Suppression of Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis
Authors: Cheng Tai-Shan , Chen Wen-Chi , Lin Ya-Yun , Tsai Chin-Hsien , Liao Chia-I , Shyu Hsin-Yi , Ko Chun-Jung , Tzeng Sheue-Fen , Huang Chun-Yin , Yang Pan-Chyr , Hsiao Pei-Wen , Lee Ming-Shyue
Published: March 2013

Curcumin has been shown to possess potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism involved in curcumin's ability to suppress prostate cancer cell invasion, tumor growth, and metastasis is not yet well understood. In this study, we have shown that curcumin can suppress epidermal growth factor (EGF)- stimulated and heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment significantly resulted in reduced matrix metalloproteinase 9 activity and downregulation of cellular matriptase, a membrane-anchored serine protease with oncogenic roles in tumor formation and invasion. Our data further show that curcumin is able to inhibit the induction effects of androgens and EGF on matriptase activation, as well as to reduce the activated levels of matriptase after its overexpression, thus suggesting that curcumin may interrupt diverse signal pathways to block the protease. Furthermore, the reduction of activated matriptase in cells by curcumin was also partly due to curcumin's effect on promoting the shedding of matriptase into an extracellular environment, but not via altering matriptase gene expression. In addition, curcumin significantly suppressed the invasive ability of prostate cancer cells induced by matriptase overexpression. In xenograft model, curcumin not only inhibits prostate cancer tumor growth and metastasis but also downregulates matriptase activity in vivo. Overall, the data indicate that curcumin exhibits a suppressive effect on prostate cancer cell invasion, tumor growth, and metastasis, at least in part via downregulating matriptase function. Cancer Prev Res; 6(5); 495–505. ©2013 AACR.
New Perspectives of Curcumin in Cancer Prevention
Authors: Park Wungki , Amin A.R.M. Ruhul , Chen Zhuo Georgia , Shin Dong M.
Published: March 2013

Numerous natural compounds have been extensively investigated for their potential for cancer prevention over the decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nonetheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here, we review the potential of curcumin in cancer prevention, its molecular targets, and mechanisms of action. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. Cancer Prev Res; 6(5); 387–400. ©2013 AACR.
Pure Mucinous Breast Carcinoma: A Favorable Subtype
Authors: Yang Meng , Li Xin , Pang Chun-Hong , Huang Lin-Ping
Published: March 2013

Background: Pure mucinous breast carcinoma is a relatively rare subtype of breast malignancy. This study is to investigate the clinical and pathologic features of pure mucinous breast carcinoma. Patients andMethods: A retrospective review of our database of patients who presented with breast cancer was performed. The medical records of 1,060 patients with invasive breast cancer who underwent surgery were reviewed. Results: 28 patients with pure mucinous breast cancer were identified. The mean age was 55.28 ± 15.73 years. 17 patients underwent modified radical mastectomy; 11 underwent breast-conserving therapy. The tumor size was T1 in 19 patients, T2 in 8 patients, and T3 in 1 patient. None of the patients had lymph node metastasis. There was no distant metastasis. 18 were stage I, and 10 were stage II. Estrogen receptor, progesterone receptor, HER-2, and P53 were positive in 96, 93, 0, and 28%, respectively. Median follow-up was 42 months (range 1-84 months). 1 patient had local recurrence. The overall survival rate was 100%. Conclusion: Pure mucinous breast carcinoma has a favorable prognosis. Less invasive treatment might be optional. Larger data samples with longer follow-up would be necessary to gain a better understanding of this disease.
HLA-A, B (Class I) and HLA-DR, DQ (Class II) Antigens in Turkish Patients with Recurrent Aphthous Ulceration and Behçet's Disease
Authors: Pekiner Filiz Namdar , Aytugar Emre , Demirel Gülderen Yanikkaya , Borahan M. Oğuz
Published: March 2013

Objective: The aims of the present study were to typify the human leukocyte antigen system (HLA)-A, B (class I) and HLA-DR, DQ (class II) antigens and to assess the frequency of the presence of these antigens in the Turkish population with recurrent aphthous ulceration (RAU) and Behçet's disease (BD) compared to healthy subjects. Subjects and Methods: Thirty patients with RAU, 30 with BD, and 15 healthy subjects were included in the study. HLA typing was performed by serology with commercial kits for HLA class I and II (One Lambda, Canoga Park, Calif., USA). Results: The HLA-A23 frequency was 26.7% in the RAU patients, which was significantly higher than the 3.3% frequency in the patients with BD (p < 0.05). The HLA-A24 frequency was 33.3% in the RAU patient group, which was significantly higher (p < 0.05) than the frequency in the healthy subjects (6.7%). Significantly higher frequencies (46.7%) of HLA-A30 were found in the healthy subjects compared to the BD (13.3%) and RAU (3.3%) patients (p < 0.05 and p < 0.01, respectively). A higher frequency of HLA-B13 was observed in the RAU (23.3%) patients compared to the BD (0%) patients (p < 0.01). A decrease was observed in HLA-DR10 and HLA-DR17 in the RAU patients (p < 0.05), while a higher frequency of HLA-DR10 was observed in the BD patients compared to the RAU patients (p < 0.01). Conclusions: These results showed that RAU and BD were not in the same spectrum and the involvement of other genetic and/or environmental factors might be responsible for the development of these diseases and/or disease progression.
Differences in Drug Therapy between Dementia Disorders in the Swedish Dementia Registry: A Nationwide Study of over 7,000 Patients
Authors: Johnell Kristina , Religa Dorota , Eriksdotter Maria
Published: March 2013

Background/Aims: We aimed to study whether there are differences between dementia disorders and the use of anti-dementia drugs and antipsychotics (neuroleptics) in a large population of dementia patients. Methods: Information about dementia disorders was obtained from the national Swedish Dementia Registry (SveDem) 2007-2010 (n = 7,570). Multivariate logistic regression analysis was performed to investigate the association between dementia disorders and the use of anti-dementia drugs and antipsychotics, after adjustment for age, sex, residential setting, living alone, MMSE score and number of other drugs (a proxy for overall co-morbidity). Results: More than 80% of the Alzheimer's disease (AD) and 86% of dementia with Lewy bodies (DLB) patients used anti-dementia drugs. Women were more likely than men to be treated with cholinesterase inhibitors. A higher MMSE score was positively associated with the use of cholinesterase inhibitors, but negatively associated with NMDA receptor antagonists and antipsychotics. Use of antipsychotics was 6% overall; however, it was 16% in DLB patients with an adjusted odds ratio of 4.2 compared to AD patients. Conclusion: Use of anti-dementia drugs in AD was in agreement with Swedish guidelines. However, use of antipsychotics in DLB patients was high, which might be worrying given the susceptibility of DLB patients to antipsychotics.
Complete Pathological Remission of Locally Advanced, Unresectable Pancreatic Cancer (LAPC) after Intensified Neoadjuvant Chemotherapy
Authors: Hartlapp Ingo , Müller Justus , Kenn Werner , Steger Ulrich , Isbert Christoph , Scheurlen Michael , Germer Christoph-Thomas , Einsele Hermann , Kunzmann Volker
Published: March 2013

Background: Unresectable locally advanced pancreatic cancer (LAPC) has an extremely poor prognosis. Results of neoadjuvant (radio-)chemotherapy approaches aiming at achieving resectability are currently not satisfactory. Case Report: We report the case of a 67-year-old woman with histologically confirmed pancreas carcinoma that was not resectable on first surgical exploration who achieved a well-documented complete pathological remission (pCR). The carcinoma became resectable after consecutive neoadjuvant treatment with nanoparticle albumin-bound (nab)-paclitaxel/gemcitabine and FOLFIRINOX chemotherapy regimens. Conclusion: This is the first reported LAPC case in which neoadjuvant chemotherapy alone has been shown to lead to demonstrated pCR. CA19-9 levels, but not imaging criteria, were useful for response prediction and timing of the Whipple's procedure. The findings in this case suggest possible conceptual changes in the treatment approach for LAPC, and indicate that the new effective chemotherapy regimens should be integrated into clinical trials for LAPC.
The Impact of Computed Tomography on Early Glottic Cancer Outcomes
Authors: Mourad Waleed F. , Hu Kenneth S. , Shourbaji Rania A. , Ishihara Dan , Lin Wilson , Kumar Mahesh , Blakaj Dukagjin M. , Harrison Louis B.
Published: March 2013

Purpose: Aim of this study was to evaluate the impact of computed tomography (CT)-based simulation and planning on early glottic cancer outcomes and toxicity. Methods: This is a single-institution retrospective study of 253 patients with T1-2 glottic cancer who underwent radiation therapy (RT) from January 1998-2010. Group A (80%) underwent 2-dimensional RT (2DRT) and group B (20%) 3-dimensional RT (3DRT). 76% of patients in group A and 84% in group B had T1 cancer. The median dose and fraction size were 63 Gy and 2.25 Gy, respectively. Results: With a median follow-up of 83, 93, and 30 months for the whole cohort, group A and B, respectively, the loco-regional control (LRC) was 97.6%. The rate of LRC for T1 disease was 99.5% and for T2 disease 91%. According to the RT modality, rates of LRC were 99.4 and 100% in groups A and B for T1, and 89.8 and 100% for T2. Long-term toxicity was negligible in both groups. Kaplan-Meier Curve showed the 5-year cause-specific survival to be 100%. Chi-square and multivariate analysis tests showed a significant relationship between CT simulation (3DRT) and LRC (p < 0.0001). Conclusion: CT-based simulation and planning provided better LRC and less acute side effects compared to 2DRT.
Safety Evaluation of High-Intensity Focused Ultrasound in Patients with Pancreatic Cancer
Authors: Wang Kun , Zhu Huili , Meng Zhiqiang , Chen Zhen , Lin Junhua , Shen Yehua , Gao Huifeng
Published: March 2013

Introduction: This study was performed to analyze the safety of high-intensity focused ultrasound (HIFU) for treating pancreatic cancer. Methods: 224 cases with advanced pancreatic cancer were enrolled into this study. Real-time sonographic images were taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were monitored and recorded before, during, and after HIFU. Computed tomography or magnetic resonance imaging (MRI) was also performed before and after HIFU. Results: Serum amylase level increased in 16 cases (7.1%) 1 day after HIFU treatment, and 9 of these cases also had abnormal urinary amylase levels. Gastrointestinal (GI) dysfunction such as abdominal distension and anorexia with slight nausea was observed in 10 cases (4.5%) after HIFU treatment. 1 case with pancreatic head cancer developed obstructive jaundice 2 weeks after HIFU treatment. Vertebral injury, identified by MRI, occurred in 2 cases, although no symptoms were seen. No severe complications such as skin burns, lesion bleeding, GI tract bleeding or GI perforation were observed in any of the cases. Conclusion: For specific patients, HIFU treatment is a safe, non-invasive treatment for pancreatic cancer but requires careful preoperative preparation and exact operative performance.
Acute-Onset Endophthalmitis Caused by Alloiococcus otitidis following a Dexamethasone Intravitreal Implant
Authors: Marchino Tizana , Vela José I. , Bassaganyas Francisca , Sánchez Saskia , Buil José A.
Published: March 2013

Purpose: To report the first case of acute endophthalmitis caused by Alloiococcus otitidis after a dexamethasone intravitreal implant. Methods: A 74-year-old female was treated with intravitreal Ozurdex® in her left eye for central retinal vein occlusion (CRVO). Best-corrected visual acuity (BCVA) in the eye was 4/20. Intravitreal injection was uneventful. At 48 h after injection, she developed ocular pain and visual acuity had dropped to light perception. Endophthalmitis associated with intravitreal injection was suspected. Results: The patient did not show a favorable clinical response following systemic, intravitreal, and topical fortified antibiotics. We then performed a vitreous biopsy and removed the Ozurdex implant by pars plana vitrectomy. A vitreous culture was positive for A. otitidis. At the 2-month follow up, no inflammation was observed, but due to CRVO and probably aggravated by endophthalmitis, the fundus showed macular fibrosis. The final BCVA was finger counting at 30 cm in her left eye. Conclusions: In cases of an intravitreal implant associated with endophthalmitis, we recommend removal of the device because it may act as a permanent reservoir of organisms if it remains in the vitreous cavity.
The association of smoking with venous thrombosis in women
Authors: Wiggins Kerri L. , McKnight Barbara , Psaty Bruce M. , Rice Kenneth M. , Heckbert Susan R. , Smith Nicholas L. , Blondon Marc
Published: March 2013

The evidence for an association between smoking and venous thrombosis (VT) is inconsistent, and its mediation pathways remain to be fully elucidated. A population-based, case-control study was conducted in a large, integrated healthcare system in Washington State, USA. Cases were women aged 18–90 years who experienced a validated incident deep-vein thrombosis or pulmonary embolism between January 1, 1995, and December 31, 2009. Controls were randomly selected from members of the healthcare system. Smoking status (current, former, never) was assessed from medical records review and, for a subset, also by telephone interview. Multivariable logistic regression was used to estimate odds ratios (OR) associated with smoking status. We identified 2,278 cases and 5,927 controls. Subjects comprised mostly postmenopausal white women with a mean age of 66 years and a current smoking prevalence of 10%. Compared to never-smokers, current and former smokers were at higher risk of VT (adjusted OR 1.21, 95% confidence interval [CI] 1.02–1.44 and OR 1.15, 95%CI 1.03–1.29, respectively). These associations were attenuated with further adjustment for potential mediators (cardiovascular disease, congestive heart failure, cancer, recent hospitalisations and physical activity): OR 1.02 (95%CI 0.83–1.25) and 0.95 (95%CI 0.83–1.08), respectively. In conclusion, the modestly increased risk of VT in women who are current or former smokers might be explained by the occurrence of smoking-related diseases and decreased physical activity. Our results do not support a direct biological effect of smoking on the risk of VT that is clinically relevant.

Note: Part of this work has been presented as a poster at the 58th annual meeting of the Scientific & Standardization Committee of the ISTH in June 2012.
Antimicrobial activity of fibrinogen and fibrinogen-derived peptides – a novel link between coagulation and innate immunity
Authors: Mörgelin Matthias , Kasetty Gopinath , Olin Anders I. , Schmidtchen Artur , Herwald Heiko , Påhlman Lisa I.
Published: March 2013

Fibrinogen is a key player in the blood coagulation system, and is upon activation with thrombin converted into fibrin that subsequently forms a fibrin clot. In the present study, we investigated the role of fibrinogen in the early innate immune response. Here we show that the viability of fibrinogen-binding bacteria is affected in human plasma activated with thrombin. Moreover, we found that the peptide fragment GHR28 released from the p-chain of fibrinogen has antimicrobial activity against bacteria that bind fibrinogen to their surface, whereas non-binding strains are unaffected. Notably, bacterial killing was detected in Group A Streptococcus bacteria entrapped in a fibrin clot, suggesting that fibrinogen and coagulation is involved in the early innate immune system to quickly wall off and neutralise invading pathogens.