bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects ofBanha-sasim-tangon Dyspeptic Symptoms and Gastric Motility in Cases of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled, and Two-Center Trial
Authors: Park Jae-Woo , Ko Seok-Jae , Han Gajin , Yeo Inkwon , Ryu Bongha , Kim Jinsung
Published: June 2013

Introduction. Functional dyspepsia (FD) is highly prevalent, and no standard treatments exist for this condition. Herbal prescriptions are widely used to treat FD. In traditional Korean medicine,Banha-sasim-tang(BST) is a famous herbal prescription for dyspepsia. This study aimed to evaluate the efficacy of BST and to examine the relationship between gastric slow waves and dyspeptic symptoms.Materials and Methods. In total, 100 FD patients were recruited; BST or placebo was administered for 6 weeks. The gastrointestinal symptom scale, FD-related quality of life scale, and frequency or power variables regarding gastric slow waves were measured at 0, 6, and 14 weeks.Results. There were no significant differences in the overall dyspeptic symptoms or quality of life between the BST and placebo groups. However, early satiety was significantly improved in the BST group (P=0.009, at 6 weeks by intention-to-treat analysis). Abnormal gastric dysrhythmias and power ratios were also significantly improved by BST.Conclusion. BST had no significant effects on FD. However, early satiety appeared to improve after BST administration. Electrogastrography may be a useful technique for assessing changes in gastric motility dysfunction after interventions for FD. Further investigation focused on specific symptoms or subtypes of FD is required.
Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability
Authors: Narala Arjun , Veerabrahma Kishan
Published: June 2013

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism.
Lyme Disease and Oncothermia
Authors: Zais Ortwin
Published: June 2013

Lyme disease is a tick-borne disease with multiple organ failures, and systemic disorders. Dramatic change becomes apparent in the chronic phase of the disease. Chronic fatigue syndrome, lapse of concentration, depression, joint pain, and muscle pain are a few, but major clinical symptoms characterizing the disease. The human immune system is defenseless. Borrelia uses various mechanisms to escape from immunoattacks or antibiotic therapies. This “stealth phenomenon” needs new therapeutic principles to be interrupted. Our objective in this paper is to study the effect of oncothermia, which is a well-established oncological therapy, on Lyme disease. First, in our present work, we definitely concentrate on the quality of life of the patients.
Control over Drug Acquisition, Preparation, and Injection: Implications for HIV and HCV Risk among Young Female Injection Drug Users
Authors: Wagner Karla D. , Jackson Bloom Jennifer , Hathazi Susan Dodi , Sanders Bill , Lankenau Stephen E.
Published: June 2013

Young female injection drug users (IDUs) are at risk for HIV/HCV, and initiating the use of a new drug may confer additional and unexpected risks. While gender differences in the social context of injection drug use have been identified, it is unknown whether those differences persist during the initiation of a new drug. This mixed-methods study examined the accounts of 30 young female IDUs in Los Angeles, CA, USA from 2004 to 2006, who described the social context of initiating injection drug use and initiating ketamine injection. The analysis aimed to understand how the social context of young women’s injection events contributes to HIV/HCV risk. Women’s initiation into ketamine injection occurred approximately 2 years after their first injection of any drug. Over that time, women experienced changes in some aspects of the social context of drug injection, including the size and composition of the using group. A significant proportion of women described injection events characterized by a lack of control over the acquisition, preparation, and injection of drugs, as well as reliance on friends and sexual partners. Findings suggest that lack of control over drug acquisition, preparation, and injection may elevate women’s risk; these phenomena should be considered as a behavioral risk factor when designing interventions.
Adults with Greater Weight Satisfaction Report More Positive Health Behaviors and Have Better Health Status Regardless of BMI
Authors: Blake Christine E. , Hébert James R. , Lee Duck-chul , Adams Swann A. , Steck Susan E. , Sui Xuemei , Kuk Jennifer L. , Baruth Meghan , Blair Steven N.
Published: June 2013

Background.Prior studies suggest that weight satisfaction may preclude changes in behavior that lead to healthier weight among individuals who are overweight or obese.Objective.To gain a better understanding of complex relationships between weight satisfaction, weight-related health behaviors, and health outcomes.Design.Cross-sectional analysis of data from the Aerobics Center Longitudinal Study (ACLS).Participants.Large mixed-gender cohort of primarily white, middle-to-upper socioeconomic status (SES) adults with baseline examination between 1987 and 2002 (n=19,003).Main Outcome Variables.Weight satisfaction, weight-related health behaviors, chronic health conditions, and clinical health indicators.Statistical Analyses Performed.Chi-square test,t-tests, and linear and multivariate logistic regression.Results.Compared to men, women were more likely to be dieting (32% women; 18% men) and had higher weight dissatisfaction. Men and women with greater weight dissatisfaction reported more dieting, yo-yo dieting, and snacking and consuming fewer meals, being less active, and having to eat either more or less than desired to maintain weight regardless of weight status. Those who were overweight or obese and dissatisfied with their weight had the poorest health.Conclusion.Greater satisfaction with one’s weight was associated with positive health behaviors and health outcomes in both men and women and across weight status groups.
Relation of Visceral and Subcutaneous Adipose Tissue to Bone Mineral Density in Chinese Women
Authors: Wang Ling , Wang Wei , Xu Li , Cheng Xiaoguang , Ma Yimin , Liu Dan , Guo Zhe , Su Yongbin , Wang Qianqian
Published: June 2013

The relationship between adipose and bone tissues is still being debated. The purpose of our study was to evaluate whether the distribution and volume of abdomen adipose tissue are correlated to trabecular bone mineral density in the lumbar spine. In this cross-sectional study, 320 Chinese women, being divided into two groups according to age ≥55 years and <55 years, were evaluated with quantitative computed tomography (QCT) of the spine to simultaneously evaluate the average trabecular BMD of L2–L4, VAT, and SAT. Possible covariates of height, weight, age, and comorbidities were considered. In the <55-year-old sample, multiple linear regression analyses indicated that VAT volume was negatively correlated to trabecular BMD (Pvalue = 0.0003) and SAT volume had no correlation to trabecular BMD. In contrast, there was no significant correlation between VAT or SAT and BMD in the ≥55-year-old sample. Our results indicate that high VAT volume is associated with low BMD in Chinese women aged <55 years and SAT has no relation with BMD.
RET-MAC: A New Fair MAC Protocol for Underwater Acoustic Sensor Network
Authors: Xiong Shuming , Yuan Cheng , Tian Lixin , Zhan Yongzhao
Published: June 2013

In underwater acoustic sensor networks (UASNs), the propagation delay of acoustic signals is much longer than Radio Frequency (RF). There is spatial unfairness problem caused by space-time uncertainty. Hence, the design of Medium Access Control (MAC) is a challenging issue. In underwater, it not only considers transmission time but also takes location into account. In this paper, we propose Response to the Earliest Transmitter of RTS MAC (RET-MAC) protocol to solve the problem. RET-MAC adopts adaptive RTS Contention Phase (RTS CP) to determine the earliest transmitter of RTS. And CTS Delay Phase (CTS DP) is added to postpone sending CTS in order to avoid collision. In addition, we propose CTS back-off mechanism to adjust the length of CTS DP as needed. Contention back-off mechanism is used to reduce network congestion and increase fairness further. The simulation results show that our scheme can achieve higher fairness and throughput; at the same time it also guarantees lower energy consumption and delay.
Multiple Nonlinear Oscillations in a𝔻3×𝔻3-Symmetrical Coupled System of Identical Cells with Delays
Authors: Hu Haijun , Liu Li , Mao Jie
Published: June 2013

A coupled system of nine identical cells with delays and𝔻3×𝔻3-symmetry is considered. The individual cells are modelled by a scalar delay differential equation which includes linear decay and nonlinear delayed feedback. By analyzing the corresponding characteristic equations, the linear stability of the equilibrium is given. We also investigate the simultaneous occurrence of multiple periodic solutions and spatiotemporal patterns of the bifurcating periodic oscillations by using the equivariant bifurcation theory of delay differential equations combined with representation theory of Lie groups. Numerical simulations are carried out to illustrate our theoretical results.
Laser Acupuncture: Two Acupoints (Baihui, Neiguan) and Two Modalities of Laser (658 nm, 405 nm) Induce Different Effects in Neurovegetative Parameters
Authors: Litscher Gerhard , Wang Lu , Wang Xiaoyu , Gaischek Ingrid
Published: June 2013

There are only few scientific publications dealing with the basic investigation of the effects of only one or two acupoints or comparing one single point with another single point, using different stimulation methods in the same persons. The aim of this needle-controlled, randomized crossover study was to investigate the neurovegetative parameters heart rate (HR) and heart rate variability (HRV) using two different acupoints, Baihui (GV20) and Neiguan (PC6), in separate sessions. We investigated 11 healthy volunteers (3 m, 8 f) with a mean age ± SD of22.9±2.8years. The two acupoints were stimulated for 10 minutes each with manual needle acupuncture, red laser acupuncture (658 nm), and violet laser acupuncture (405 nm), in randomized order. Needle and red laser stimulation of the Baihui acupoint decreased HR significantly. Only violet laser stimulation at the Neiguan acupoint induced a significant increase of total HRV. Further studies using other neurovegetative parameters and more volunteers are necessary to confirm the preliminary results.
Analysis of the Processes in Spent Fuel Pools in Case of Loss of Heat Removal due to Water Leakage
Authors: Kaliatka Algirdas , Ognerubov Viktor , Vileiniškis Virginijus , Ušpuras Eugenijus
Published: June 2013

The safe storage of spent fuel assemblies in the spent fuel pools is very important. These facilities are not covered by leaktight containment; thus, the consequences of overheating and melting of fuel in the spent fuel pools can be very severe. On the other hand, due to low decay heat of fuel assemblies, the processes in pools are slow in comparison with processes in reactor core during LOCA accident. Thus, the accident management measures play a very important role in case of some accidents in spent fuel pools. This paper presents the analysis of possible consequences of fuel overheating due to leakage of water from spent fuel pool. Also, the accident mitigation measure, the late injection of water was evaluated. The analysis was performed for the Ignalina NPP Unit 2 spent fuel pool, using system thermal hydraulic code for severe accident analysis ATHLET-CD. The phenomena, taking place during such accident, are discussed. Also, benchmarking of results of the same accident calculation using ASTEC and RELAP/SCDAPSIM codes is presented here.
Protein Profiling and Histone Deacetylation Activities in Somaclonal Variants of Oil Palm (Elaeis guineensis Jacq.)
Authors: Yaacob Jamilah Syafawati , Loh Hwei-San , Mat Taha Rosna
Published: June 2013

Mantled fruits as a result of somaclonal variation are often observed from the oil palm plantlets regenerated via tissue culture. The mantling of fruits with finger‐like and thick outer coating phenotypes significantly reduces the seed size and oil content, posing a threat to oil palm planters, and may jeopardize the economic growth of countries that depend particularly on oil palm plantation. The molecular aspects of the occurrence of somaclonal variations are yet to be known, possibly due to gene repression such as DNA methylation, histone methylation and histone deacetylation. Histone deacetylases (HDACs), involved in eukaryotic gene regulation by catalyzing the acetyl groups are removal from lysine residues on histone, hence transcriptionally repress gene expression. This paper described the total protein polymorphism profiles of somaclonal variants of oil palm and the effects of histone deacetylation on this phenomenon. Parallel to the different phenotypes, the protein polymorphism profiles of the mantled samples (leaves, fruits, and florets) and the phenotypically normal samples were proven to be different. Higher HDAC activity was found in mantled leaf samples than in the phenotypically normal leaf samples, leading to a preliminary conclusion that histone deacetylation suppressed gene expression and contributed to the development of somaclonal variants.
Toxic Epidermal Necrolysis and Graft-versus-Host Reaction: Revisiting a Puzzling Similarity
Authors: Piérard G. E. , Hermanns-Lê T. , Paquet P. , Rousseau A. F. , Delvenne P. , Piérard-Franchimont C.
Published: June 2013

Drug-induced toxic epidermal necrolysis (TEN) and acute cutaneous graft-versus-host reaction (GVHR) under immunopreventive therapy share some histopathological resemblance. So far, there are no serum biomarkers and no immunohistochemical criteria distinguishing with confidence and specificity the skin lesions of TEN and GVHR. Both diseases present as an inflammatory cell-poor necrotic reaction of the epidermis. This report compares three sets of 15 immunostaining patterns found in TEN, GVHR, and partial thickness thermal burns (PTTB), respectively. Three series of 17 skin biopsies were scrutinized. Irrespective of the distinct causal pathobiology of TEN and GVHR, similar secondary effector cells were recruited in lesional skin. Burns were less enriched in cells of the monocyte-macrophage disease. These cells likely exert deleterious effects in TEN and GVHR and cannot be simply regarded as passive bystanders. These life-threatening conditions are probably nursed, at least in part, by macrophages.
Evaluation of Circle Diameter by Distributed Tactile Information in Active Tracing
Authors: Nakamoto Hiroyuki , Kobayashi Futoshi , Kojima Fumio
Published: June 2013

Active touch with voluntary movement on the surface of an object is important for human to obtain the local and detailed features on it. In addition, the active touch is considered to enhance the human spatial resolution. In order to improve dexterity performance of multifinger robotic hands, it is necessary to study an active touch method for robotic hands. In this paper, first, we define four requirements of a tactile sensor for active touch and design a distributed tactile sensor model, which can measure a distribution of compressive deformation. Second, we suggest a measurement process with the sensor model, a synthesis method of distributed deformations. In the experiments, a five-finger robotic hand with tactile sensors traces on the surface of cylindrical objects and evaluates the diameters. We confirm that the hand can obtain more information of the diameters by tracing the finger.
The Effect of Different Strategies and the Structure on Opinion Formation
Authors: Ju Cheng , Cao Yang , Zhou Pengcheng
Published: June 2013

This paper defines two different ways of the process of the opinion formation and focuses on the effect of the proportion of the two strategies of process and the structure of the network. A multiopinion model is proposed in this paper, which includes two strategies of opinion formation. At the first part, the change of the structured network and the change of the single node are used as two strategies of the process of the opinion formation. We focus on how the proportion of the two strategies can affect the outcome of the process. At the second part, as the proportion of the two strategies is fixed, the edges are dense in the community and sparse outside. Thus we can construct a bifurcation diagram to be verified through experimental study. The phase transition is studied in the network which contains more than four opinions and two strategies of process. Our results show that the size of the group and the dense of edges are the two important features for the process of opinion formation.
Optimal Portfolio of Corporate Investment and Consumption Problem under Market Closure: Inflation Case
Authors: Huang Zongyuan , Zhang Detao
Published: June 2013

We present the model of corporate optimal investment with consideration of the influence of inflation and the difference between the market opening and market closure. In our model, the investor has three market activities of his or her choice: investment in project A, investment in project B, and consumption. The optimal strategy for the investor is obtained using the Hamilton-Jacobi-Bellman equation which is derived using the dynamic programming principle. Further along, a specific case, the Hyperbolic Absolute Risk Aversion case, is discussed in detail, where the explicit optimal strategy can be obtained using a very simple and direct method. At the very end, we present some simulation results along with a brief analysis of the relationship between the optimal strategy and other factors.
Synthesis and Characterization of Polyurethane-Nanoclay Composites
Authors: Nayani Manasa , Gunashekar Subhashini , Abu-Zahra Nidal
Published: June 2013

In this study polyurethane (PUR)-nanoclay composites were synthesized using methylene diphenyl diisocyanate, polyol, and hectorite clay. The weight percentage of hectorite clay was varied at three different levels to study its effect on the properties of the thermoplastic polyurethane nanocomposite. The nanocomposite polyurethane foam was synthesized in a 2-step reaction process. The first step involved the addition and dispersion of nanoclay into the isocyanate. The mixture was then mixed with the polyol, and the foam was cast in a preheated closed mold. The PUR-nanocomposite foams were analyzed for cell structure, physical, mechanical, and thermal properties. The composite foam showed significant increase in tensile and flexural strengths, abrasion resistance, and thermal properties.
Neuroprotective Effect of Tea Polyphenols on Oxyhemoglobin Induced Subarachnoid Hemorrhage in Mice
Authors: Mo Haizhen , Chen Ying , Huang Liyong , Zhang Hao , Li Juxiang , Zhou Wenke
Published: June 2013

Tea polyphenols are of great benefit to the treatment of several neurodegenerative diseases. In order to explore the neuroprotective effects of tea polyphenols and their potential mechanisms, an establishedin vivosubarachnoid hemorrhage (SAH) model was used and alterations of mitochondrial function, ATP content, and cytochromec(cytc) in cerebral cortex were detected. This study showed that the alteration of mitochondrial membrane potential was an early event in SAH progression. The trend of ATP production was similar to that of mitochondrial membrane potential, indicating that the lower the mitochondrial membrane potential, lesser the ATP produced. Due to mitochondrial dysfunction, more cytcwas released in the SAH group. Interestingly, the preadministration of tea polyphenols significantly rescued the mitochondrial membrane potential to basal level, as well as the ATP content and the cytclevel in the brain cortex 12 h after SAH. After pretreatment with tea polyphenols, the neurological outcome was also improved. The results provide strong evidence that tea polyphenols enhance neuroprotective effects by inhibiting polarization of mitochondrial membrane potential, increasing ATP content, and blocking cytcrelease.
New Insights into the Role of the Immune Microenvironment in Breast Carcinoma
Authors: de la Cruz-Merino Luis , Barco-Sánchez Antonio , Henao Carrasco Fernando , Nogales Fernández Esteban , Vallejo Benítez Ana , Brugal Molina Javier , Martínez Peinado Antonio , Grueso López Ana , Ruiz Borrego Manuel , Codes Manuel de Villena Manuel , Sánchez-Margalet Víctor , Nieto-García Adoración , Alba Conejo Emilio , Casares Lagar Noelia , Ibáñez Martínez José
Published: June 2013

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.
Klippel-Trenaunay Syndrome Causing Life-Threatening GI Bleeding: A Case Report and Review of the Literature
Authors: Samo Salih , Sherid Muhammed , Husein Husein , Sulaiman Samian , Yungbluth Margaret , Vainder John A.
Published: June 2013

Klippel-Trenaunay syndrome (KTS) is a rare congenital syndrome of vascular malformations and soft tissue and bone hypertrophy. Vascular malformations can affect multiple organ systems. Involvement of the gastrointestinal (GI) tract is uncommon in KTS, but it can be a source of life-threatening bleeding. We report a case of a 32-year-old male with a known diagnosis of KTS who presented with a life-threatening rectal bleeding and was treated with proctosigmoidectomy and massive blood products transfusion. He expired after a long hospitalization. We then review the literature on KTS and management of some of its complications.
Some Common Fixed Point Results for Rational Type Contraction Mappings in Complex Valued Metric Spaces
Authors: Chandok Sumit , Kumar Deepak
Published: June 2013

We prove some common fixed point theorems for two pairs of weakly compatible mappings satisfying a rational type contractive condition in the framework of complex valued metric spaces. The proved results generalize and extend some of the known results in the literature.
Uniqueness, Born Approximation, and Numerical Methods for Diffuse Optical Tomography
Authors: Kwon Kiwoon
Published: June 2013

Diffuse optical tomogrpahy (DOT) is to find optical coefficients of tissue using near infrared light. DOT as an inverse problem is described and the studies about unique determination of optical coefficients are summarized. If a priori information of the optical coefficient is known, DOT is reformulated to find a perturbation of the optical coefficients inverting the Born expansion which is an infinite series expansion with respect to the perturbation and the a priori information. Numerical methods for DOT are explained as methods inverting first- or second-order Born approximation or the Born expansion itself.
Land Use Change from Biofuels Derived from Forest Residue: A Case of Washington State
Authors: Brent Daniel , Rabotyagov Sergey
Published: June 2013

Biofuel policy in the United States is transitioning away from corn towards second-generation biofuels in part because of the debate over environmental damages from indirect land use change. We combine a spatially explicit parcel level model for land use change in Washington State with simulations for biofuel policy aimed at utilizing forest residue as feedstock. Using a spatially explicit model provides greater precision in measuring net returns to forestland and development and indicates which areas will be most impacted by biofuel policy. The effect of policy is simulated via scenarios of increasing net returns to forestry and of siting feedstock-processing plants. Our results suggest that forestland will increase from such a policy, leading to a net reduction in atmospheric carbon from indirect land use change. This is in contrast to the experience of corn ethanol where the change in carbon emissions is potentially positive and large in magnitude.
Diagnostically Relevant Molecular Markers in Head and Neck Neoplasms
Authors: Varghese Soma Susan , Mathew Philips , Jose Jithin
Published: June 2013

Tumor markers are grouped into diagnostic and prognostic markers. Specific diagnostic markers appear extensively in cells of a particular neoplasm and not in other tumors. These markers can be used to assess the cellular lineage and histogenic origin of various neoplasms. Thus, diagnostic markers can be used for the confirmatory diagnosis of various tumors. This paper reviews the literature on various diagnostic markers and aims to group them based on the cellular lineage of neoplasms.
Dissection of Mechanisms of a Chinese Medicinal Formula: Danhong Injection Therapy for Myocardial Ischemia/Reperfusion InjuryIn VivoandIn Vitro
Authors: Guan Yue , Yin Ying , Zhu Yan-Rong , Guo Chao , Wei Guo , Duan Jia-Lin , Wang Yan-Hua , Zhou Dan , Quan Wei , Weng Yan , Xi Miao-Miao , Wen Ai-Dong
Published: June 2013

Traditional Chinese medicine uses a systemic treatment approach, targeting multiple etiological factors simultaneously. Danhong injection (DHI), a very popular Chinese medicine injection, is reported to be effective for many cardiovascular conditions. The primary active ingredients of DHI, and their systemic and interrelated mechanism have not been evaluated in an established myocardial ischemia/reperfusion (MI/R) model. We identified the main active constituents in DHI, including hydroxysafflor yellow A (A), salvianolic acid B (B), and danshensu (C), by HPLC fingerprint analysis and assessed their effect on MI/R rats and cardiomyocytes. These 3 compounds and DHI all decreased the levels of IL-1, TNF-α, and MDA, increased those of IL-10 and SOD activityin vivoandin vitro, and had antiapoptotic effects, as shown by flow cytometric analysis and TUNEL assay. Moreover, these compounds increased phosphorylation of Akt and ERK1/2 in cardiomyocytes. Interestingly, we found compound A exerted a more prominent anti-inflammatory effect than B and C, by decreasing NF-κB levels; compound B had more powerful antioxidative capacity than A and C, by increasing Nrf2 expression; compound C had stronger antiapoptotic ability than A and B, by lowering caspase-3 activity. Our results elucidate the mechanisms by which DHI protects against MI/R induced injury.
Amplification of the MET Receptor Drives Resistance to Anti-EGFR Therapies in Colorectal Cancer
Authors: Bardelli Alberto , Corso Simona , Bertotti Andrea , Hobor Sebastijan , Valtorta Emanuele , Siravegna Giulia , Sartore-Bianchi Andrea , Scala Elisa , Cassingena Andrea , Zecchin Davide , Apicella Maria , Migliardi Giorgia , Galimi Francesco , Lauricella Calogero , Zanon Carlo , Perera Timothy , Veronese Silvio , Corti Giorgio , Amatu Alessio , Gambacorta Marcello , Diaz Luis A. , Sausen Mark , Velculescu Victor E. , Comoglio Paolo , Trusolino Livio , Di Nicolantonio Federica , Giordano Silvia , Siena Salvatore
Published: June 2013

EGF receptor (EGFR)-targeted monoclonal antibodies are effective in a subset of metastatic colorectal cancers. Inevitably, all patients develop resistance, which occurs through emergence of KRAS mutations in approximately 50% of the cases. We show that amplification of the MET proto-oncogene is associated with acquired resistance in tumors that do not develop KRAS mutations during anti-EGFR therapy. Amplification of the MET locus was present in circulating tumor DNA before relapse was clinically evident. Functional studies show that MET activation confers resistance to anti-EGFR therapy both in vitro and in vivo. Notably, in patient-derived colorectal cancer xenografts, MET amplification correlated with resistance to EGFR blockade, which could be overcome by MET kinase inhibitors. These results highlight the role of MET in mediating primary and secondary resistance to anti-EGFR therapies in colorectal cancer and encourage the use of MET inhibitors in patients displaying resistance as a result of MET amplification.

Significance: Amplification of the MET proto-oncogene is responsible for de novo and acquired resistance to anti-EGFR therapy in a subset of colorectal cancers. As multiple anti-MET therapeutic strategies are available, these findings offer immediate novel opportunities to design clinical studies. Cancer Discov; 3(6); 658–73. ©2013 AACR.

This article is highlighted in the In This Issue feature, p. 591
Total Lipid Management and Cardiovascular Disease in the Dyslipidemia International Study
Authors: Ferrières Jean , Amber Vian , Crisan Oliviu , Chazelle François , Jünger Claus , Wood David
Published: June 2013

Objectives: Despite statin use, many patients with cardiovascular disease (CVD) are not achieving treatment goals. An international observational study was performed to estimate the prevalence of residual lipid abnormalities in statin-treated patients with CVD to assess whether lipid management requires improvement. Methods: Fasting plasma concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were recorded in 11,104 patients with atherosclerotic CVD and ≥3 months of statin therapy. Results: LDL-C and total cholesterol were not at goal levels in 41 and 46% of all patients, respectively; for patients with peripheral artery disease (PAD) only, 59 and 65%, respectively, were not at goal, and in those with coronary heart disease only, 38 and 42%, respectively, were not at goal. Patients with cerebrovascular disease only were least frequently observed to have low HDL-C (24%) and elevated triglycerides (36%). Overall, elevated LDL-C was the most frequent lipid anomaly observed, and preexisting heart failure was strongly and positively associated with dyslipidemia. Conclusions: Approximately two fifths of statin-treated patients with CVD are not reaching lipid goals or have abnormal lipid levels, while patients with PAD could particularly benefit from improved lipid management. In addition to targeting LDL-C, new evidence-based approaches are needed to target low HDL-C and elevated triglycerides.
Uric Acid Levels and All-Cause Mortality in Peritoneal Dialysis Patients
Authors: Feng Sheng , Jiang Linseng , Shi Yongbing , Shen Huaying , Shi Xiaosong , Jin Donghua , Zeng Ying , Wang Zhi
Published: June 2013

Background: Epidemiological studies have shown that hyperuricemia is associated with all-cause and cardiovascular mortality in chronic kidney disease (CKD) and hemodialysis patients. Our study investigated the influence of serum uric acid (UA) levels on survival in peritoneal dialysis (PD) patients. Methods: This was a retrospective study involving 156 subjects who had undergone PD. The patient demographics, etiology of ESRD, comorbid conditions and other laboratory parameters were collected. The subjects were divided into three groups according to their serum UA concentrations (group 1, the lowest quartile; group 2, the middle quartiles; group 3, the highest quartile). The risk of death was calculated using a multivariate Cox regression model. Results: There were 41 deaths during a follow-up period of 31.3±17.5 months. Compared with group 2, which had a mortality rate of 5.7 per 1000 person-months, the mortality rates were higher in group 1 (14.3 per 1000 person-months, p<0.05) and group 3 (13.3 per 1000 person-months, p<0.05). A multivariable Cox regression model revealed that age, serum albumin, diabetes mellitus (DM), hypertensive nephropathy, residual renal function and UA group were factors associated with mortality in the PD patients. Using group 2 as a reference, the hazard ratio (HR) of mortality was found to be 1.15 (95% confidence interval [CI] 0.20-2.57, p>0.05) for group 1 and 2.96 (95% CI 1.29-6.80, p=0.01) for group 3. Conclusions: In PD patients, a higher serum UA level is related to increased mortality and is an independent risk factor for all-cause mortality. Uric acid levels and all-cause mortality in peritoneal dialysis patients.
Attenuation of Conducted Vasodilation in Skeletal Muscle Arterioles during Hyperhomocysteinemia
Authors: Givvimani S. , Narayanan N. , Armaghan F. , Pushpakumar S. , Tyagi S.C.
Published: June 2013

Background: Vasomotor responses conducted from terminal arterioles to proximal vessels may contribute to match tissue demands and blood supply during skeletal muscle contraction. Conduction of vasodilatation (CVD) from distal resistance arterioles to the proximal arterioles and feeding arteries during metabolic demand is mediated by intercellular gap junctions in the vascular endothelium. The role of hyperhomocysteinemia (HHcy) in the musculoskeletal system during CVD is unclear. We hypothesize that during HHcy, there is impaired CVD due to decreased expression of endothelial-associated connexins and thus decreased tissue perfusion to the contracting skeletal muscles. Methods: CVD studies were performed in a gluteus maximus muscle preparation of wild-type (C57BL6/J) and CBS-/+ (HHcy) mice using intravital microscopy. Expression of connexins and myostatin protein (an antiskeletal muscle statin) was studied by Western blot and immunohistochemistry methods. Tissue perfusion to acetylcholine was assessed by the laser Doppler technique. Results: There was decreased CVD and tissue perfusion in response to acetylcholine in CBS-/+ mice compared to wild-type controls. There was decreased expression of connexins 37, 40 and 43 and increased expression of myostatin in CBS-/+ mice compared to wild-type controls. Conclusion: Our findings suggest that CVD in skeletal muscle is decreased during HHcy due to decreased expression of gap junction connexins.
Oxidative Stress and Cell Senescence Combine to Cause Maximal Renal Tubular Epithelial Cell Dysfunction and Loss in an in vitro Model of Kidney Disease
Authors: Small David M. , Bennett Nigel C. , Roy Sandrine , Gabrielli Brian G. , Johnson David W. , Gobe Glenda C.
Published: June 2013

Background: The incidence and cost of chronic kidney disease (CKD) are increasing. Renal tubular epithelial cell dysfunction and attrition, involving increased apoptosis and cell senescence, are central to the pathogenesis of CKD. The aim here was to use an in vitro model to investigate the separate and cumulative effects of oxidative stress, mitochondrial dysfunction and cell senescence in promoting loss of renal mass. Methods: Human kidney tubular epithelial cells (HK2) were treated with moderate hydrogen peroxide (H2O2) for oxidative stress, with or without cell cycle inhibition (apigenin, API) for cell senescence. Adenosine triphosphate (ATP) and oxidative stress were measured by ATP assay, lipid peroxidation, total antioxidant capacity, mitochondrial function with confocal microscopy, MitoTracker Red CMXRos and live cell imaging with JC-1. In parallel, cell death and injury (i.e. apoptosis and Bax/Bcl-XL expression, lactate dehydrogenase), cell senescence (SA-β-galactosidase) and renal regenerative ability (cell proliferation), and their modulation with the anti-oxidant N-acetyl-cysteine (NAC) were investigated. Results: H2O2 and API, separately, increased oxidative stress and mitochondrial dysfunction, apoptosis and cell senescence. Although API caused cell senescence, it also induced oxidative stress at levels similar to H2O2 treatment alone, indicating that senescence and oxidative stress may be intrinsically linked. When H2O2 and API were delivered concurrently, their detrimental effects on renal cell loss were compounded. The antioxidant NAC attenuated apoptosis and senescence, and restored regenerative potential to the kidney. Conclusion: Oxidative stress and cell senescence both cause mitochondrial destabilization and cell loss and contribute to the development of the cellular characteristics of CKD.
Hypertriglyceridemic Waist is Associated with Increased Carotid Atherosclerosis in Chronic Kidney Disease Patients
Authors: Zhe Xingwei , Bai Yunkai , Cheng Ying , Xiao Hua , Wang Dan , Wu Yan , Huang Xiaoyan , Tian Xinkui , Wang Tao
Published: June 2013

Background: Patients with chronic kidney disease (CKD) have an unacceptably high risk of death, primarily as a result of cardiovascular disease (CVD). The ‘hypertriglyceridemic waist' phenotype has been proposed as a simple and strong predictor of CVD risk. Therefore, we investigated the relationship between the hypertriglyceridemic waist phenotype and carotid atherosclerosis in CKD patients. Methods: In a cross-sectional study, we enrolled 785 prevalent CKD patients [416 males, aged 44.6 years (21.7-69.4), glomerular filtration rate 52.5 ml/min/1.73 m2 (5.3-119.4)]. We divided the patients into three groups: group 1: waist circumference >90 cm in men or >85 cm in women and triglycerides ≥2 mmol/l (n = 109); group 3: waist circumference ≤90 cm in men or ≤85 cm in women and triglycerides <2 mmol/l (n = 379), and group 2: the remaining patients (n = 297). Routine biochemical parameters and carotid artery intima-media thickness (IMT) were measured. Results: The prevalence of the hypertriglyceridemic waist phenotypes was 13.8% in the CKD patients. Triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol concentrations in group 1 were significantly higher than those in group 3. Carotid artery IMT of the hypertriglyceridemic waist group was the highest. Conclusion: The hypertriglyceridemic waist phenotype was associated with worse carotid atherosclerosis in CKD patients. This suggests that the hypertriglyceridemic waist phenotype may be useful for predicting CVD risk in CKD patients.
Cell Projections and Extracellular Matrix Cross the Interstitial Interface within the Renal Stem/Progenitor Cell Niche: Accidental, Structural or Functional Cues?
Authors: Minuth Will W. , Denk Lucia
Published: June 2013

Background: During nephron induction, morphogenetic molecules are reciprocally exchanged between epithelial and mesenchymal stem/progenitor cells within the renal stem/progenitor cell niche. That these molecules remain concentrated, it is assumed that both cell populations stand in close contact to each other. However, recently published data illustrate that epithelial and mesenchymal cells are separated by an astonishingly wide interstitial interface. Methods: To gain deeper morphological insights into the spatial distribution of mesenchymal and epithelial stem/progenitor cells, the embryonic zone of neonatal rabbit kidney was fixed either with glutaraldehyde (GA) or in a combination with cupromeronic blue, ruthenium red or tannic acid. Transmission electron microscopy was then performed on exactly orientated sections. Results: Conventional fixation with GA illustrates that epithelial and mesenchymal stem/progenitor cells are separated by a bright but inconspicuously looking interstitial interface. In contrast, fixation of specimens in GA containing cupromeronic blue, ruthenium red or tannic acid elucidates that part of the interstitial interface exhibits a special extracellular matrix extending like woven strands between mesenchymal and epithelial stem/progenitor cells. In parallel, filigree projections from mesenchymal stem/progenitor cells cross the interstitial interface to penetrate the basal lamina of epithelial cells. Fusion of the plasma membranes cannot be observed. Instead, touching mesenchymal cell projections form a cone at the contact site with tunneling nanotubes. Conclusions: The results demonstrate that the contact between mesenchymal and epithelial stem/progenitor cells does not form accidentally but physiologically and appears to belong to a suspected system involved in the exchange of morphogenetic information.
The Association between Parathyroid Hormone Levels and Hemoglobin in Diabetic and Nondiabetic Participants in the National Kidney Foundationʼs Kidney Early Evaluation Program
Authors: Memon Imran , Norris Keith C. , Bomback Andrew S. , Peralta Carmen , Li Suying , Chen Shu-Cheng , McCullough Peter A. , Whaley-Connell Adam , Jurkovitz Claudine , Tamura Manjula Kurella , Saab Georges ,   for the Kidney Early Evaluation Program Investigators
Published: June 2013

Background: Both anemia and secondary hyperparathyroidism are reflections of hormonal failure in chronic kidney disease (CKD). While the association of elevated levels of parathyroid hormone (PTH) and anemia has been studied among those with advanced CKD, less is known about this association in mild-to-moderate CKD. Methods: In a cross-sectional analysis, the relationship between PTH and hemoglobin levels was investigated in 10,750 participants in the National Kidney Foundationʼs Kidney Early Evaluation Program with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Results: In the unadjusted analysis, higher PTH levels were associated with lower hemoglobin levels. However, after multivariable adjustment for age, race, gender, smoking status, education, cardiovascular disease, diabetes, hypertension, cancer, albuminuria, BMI, baseline eGFR, calcium, and phosphorus, the direction of association changed. As compared to the first PTH quintile, hemoglobin levels were 0.09 g/dl (95% CI: 0.01-0.18), 0.15 g/dl (95% CI: 0.07-0.24), 0.18 g/dl (95% CI: 0.09-0.26), and 0.13 g/dl (95% CI: 0.07-0.25) higher for the second, third, fourth, and fifth quintiles, respectively. Similarly, each standard deviation increase in natural log transformed PTH was associated with a 0.06 g/dl (95% CI: 0.03-0.09, p = 0.0003) increase in hemoglobin. However, a significant effect modification was seen for diabetes (p = 0.0003). Each standard deviation increase in natural log transformed PTH was associated with a 0.10 g/dl (95% CI: 0.054-0.138, p < 0.0001) increase in hemoglobin, while no association was seen among those without diabetes mellitus. Conclusion: After multivariable adjustment, there was a small positive association between PTH and hemoglobin among diabetics but not among nondiabetics.
Comparing the Economic Impact of the Trans-Pacific Partnership and the Regional Comprehensive Economic Partnership
Authors: Cheong Inkyo , Tongzon Jose
Published: June 2013

Several initiatives have emerged for regional economic integration in the Asia-Pacific region. The United States has led the negotiations for the Trans-Pacific Partnership agreement, and ASEAN countries have recently started to promote the Regional Comprehensive Economic Partnership. This paper estimates the net economic impact of these initiatives by eliminating the overlapping portions of free trade agreement–related economic gains through the use of a dynamic computable general equilibrium model. The paper analyzes the economic and political feasibility of these two initiatives and assesses their economic impacts. Finally, the paper provides implications for economic integration in East Asia based on a quantitative assessment.
A checklist of cercariae (Trematoda: Digenea) in molluscs from Brazil
Authors: PINTO HUDSON ALVES , DE MELO ALAN LANE
Published: June 2013

A checklist of digenetic trematodes found in molluscs from Brazil is presented based on 127 scientific articles published after a century of studies. To date 23 families, 35 genera and 46 species of trematodes were identified infecting 25 species of molluscs in the country. Another 36 species described in the collective-group Cercaria were found in 15 species of mol-luscs and have not yet been associated with the respective adult parasites. Larvae found in 20 species of molluscs and grouped into 10 cercarian types are also listed.
Taxonomy of 'Euconnus complex'. Part II. Revision of Archiconnus Franz, Parapseudoconnus Franz and Mexiconnus gen. nov. (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: June 2013

Neotropical Scydmaeninae Archiconnus Franz and Parapseudoconnus Franz (with two subgenera) are re-defined and de-tails of their morphology are illustrated. Archiconnus mexicanus Franz is placed in a separate genus Mexiconnus gen. nov. (resulting in a new combination Mexiconnus mexicanus (Franz)). The current division of Parapseudoconnus into the nom-inotypical subgenus and a subgenus Neuraphomimus Franz is weakly supported by only minor morphological differences, but the subgenera are retained, pending further study. Archiconnus huallaganus Franz, Mexiconnus mexicanus, Parap-seudoconnus (s. str.) aberrans Franz and P. (Neuraphomimus) simulator Franz are redescribed, while detailed redescrip-tions of P. (N.) fraudulentus Franz and P. (N.) monticola Franz were not possible due to partly or entirely damaged type specimens.an� n x�8��urus; at the same time, the internal clades fit perfectly with pre-established informal morphological groups from South America, which may warrant a formal taxonomic subdivision of the genus. Additionally, the species belonging to the “provenzanoi group” clearly fit within a different taxon and should be reviewed. Also, the presence of the genus Propagurus in the ingroup could be in-terpreted by non-exclusive hypotheses: from one point of view, the genus Propagurus is nested within Pagurus, and the-refore Pagurus is not valid as currently composed; or possibly, that more than one genus should be recognized among the South American species presently assigned to Pagurus. This latter perspective accords with the proposal to restrict Pagu-rus to only a few species.