bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model
Authors: Liman Suryamin , Cheung Chi Wai , Wong Kar Lok , Tai Wai , Qiu Qiu , Ng Kwok Fu , Choi Siu Wai , Irwin Michael
Published: June 2015

Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS). Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP) model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia) in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56%) rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant). Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P<0.01) and methylprednisolone (P<0.05) groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P<0.05). Proinflammatory cytokines TNF-αand IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (allP<0.05). In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain.
Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells
Authors: Ali Khan Munawwar , Kedhari Sundaram Madhumitha , Hamza Amina , Quraishi Uzma , Gunasekera Dian , Ramesh Laveena , Goala Payal , Al Alami Usama , Ansari Mohammad Zeeshan , Rizvi Tahir A. , Sharma Chhavi , Hussain Arif
Published: June 2015

Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARβ, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.
On Efficient Link Recommendation in Social Networks Using Actor-Fact Matrices
Authors: Ciesielczyk Michał , Szwabe Andrzej , Morzy Mikołaj
Published: June 2015

Link recommendation is a popular research subject in the field of social network analysis and mining. Often, the main emphasis is put on the development of new recommendation algorithms, semantic enhancements to existing solutions, design of new similarity measures, and so forth. However, relatively little scientific attention has been paid to the impact that various data representation models have on the performance of recommendation algorithms. And by performance we do not mean the time or memory efficiency of algorithms, but the precision and recall of recommender systems. Our recent findings unanimously show that the choice of network representation model has an important and measurable impact on the quality of recommendations. In this paper we argue that the computation quality of link recommendation algorithms depends significantly on the social network representation and we advocate the use of actor-fact matrix as the best alternative. We verify our findings using several state-of-the-art link recommendation algorithms, such as SVD, RSVD, and RRI using both single-relation and multirelation dataset.
Anesthesia Related Toxic Effects on In Vitro Fertilization Outcome: Burden of Proof
Authors: Matsota Paraskevi , Kaminioti Eva , Kostopanagiotou Georgia
Published: June 2015

Management of pain and anxiety during oocyte retrieval makes anesthesia an important part of the in vitro fertilization (IVF) procedures. There are many studies investigating the influence of anesthesia on IVF success. This review article provides an overview of published data regarding the potential toxic effects of different anesthetic techniques (Loco-regional, general anesthesia (GA), and monitored anesthesia care (MAC)), different anesthetic agents, and alternative medicine approach (principally acupuncture) on the IVF outcome. From our analysis, evidence of serious toxicity in humans is not well established. Trials regarding different anesthetic techniques ended up without clear conclusions. Studies about GA came up with conflicting results. A few trials relate GA with lower pregnancy rates, although some others failed to prove this conclusion. Furthermore, detectable amounts of some anesthetic agents are measurable in the follicular fluid but these findings are not strongly associated with toxicity. MAC and Loco-regional anesthesia appear as safe alternative choices and there is evidence of improved outcome. Whereas acupuncture may provide assistance increasing IVF success according to some trials, some others could not obtain these effects. Questions about the appropriate time of application and the underlying mechanism of action are not answered yet, so further investigation should be done.
Glutathione Supplementation Attenuates Oxidative Stress and Improves Vascular Hyporesponsiveness in Experimental Obstructive Jaundice
Authors: Chen Jiaying , Wu Feixiang , Long Yue , Yu Weifeng
Published: June 2015

We investigated the protective effects and mechanism of glutathione (GSH) on vascular hyporesponsiveness induced by bile duct ligation (BDL) in a rat model. Seventy-two male Sprague-Dawley rats were randomly divided into four groups: a NS group, a GSH group, a BDL + NS group, and a BDL + GSH group. GSH was administrated into rats in the GSH and BDL + GSH groups by gastric gavage. An equal volume of normal saline was, respectively, given in the NS group and BDL + NS group. Blood was gathered for serological determination and thoracic aorta rings were isolated for measurement of isometric tension. Obstructive jaundice led to a significant increase in the serum total bilirubin, AST, and ALT levels. The proinflammatory cytokines levels (TNF-αand IL-1β), concentration of NO, and oxidative stress markers (MDA and 3-NT) were increased as well. All of those were reduced by the treatment of GSH. Meanwhile, contraction of aorta rings to NA and vasorelaxation to ACh or SNP in the BDL group rats were markedly decreased, while GSH administration reversed this change. Our findings suggested that GSH supplementation attenuated overexpressed ONOO(−) from the reaction of excessive NO withO2∙-and protected against obstructive jaundice-induced vascular hyporesponsiveness in rats.
Convergence Rate Estimate of Distributed Localization Algorithms in Wireless Sensor Networks
Authors: Pang Shujuan
Published: June 2015

Localization is one of the most important problems in wireless sensor networks. In this paper, we investigate the convergence rate estimate problem of a distributed localization algorithm which approximately formulates the localization problem as the convex feasibility problem including the consistent case and the inconsistent case. Although existing works established optimal consensus convergence analysis for this algorithm, they did not provide the convergence rate estimate. In this paper, we mainly show that for the consistent case the convergence rate of the optimal consensus will be exponential under some basic conditions, while for the inconsistent case we provide a necessary condition for the optimal consensus and a convergence rate estimate inequality. Furthermore, numerical examples are also provided to validate the established convergence and convergence rate results.
Chemerin15‐Ameliorated Cardiac Ischemia‐Reperfusion Injury Is Associated with the Induction of Alternatively Activated Macrophages
Authors: Chang Chao , Ji Qingwei , Wu Bangwei , Yu Kunwu , Zeng Qiutang , Xin Shuanli , Liu Jixiang , Zhou Yujie
Published: June 2015

Chemerin15 (C15), an endogenous anti‐inflammatory component, inhibits the activity of neutrophils and macrophages through G protein‐coupled receptor ChemR23; however, its role as well as functional mechanism in mouse myocardial ischemia/reperfusion (I/R) injury remains unknown. Methods. Sham or I/R operations were performed on C57BL/6J mice. The I/R mice received an injection of C15 immediately before reperfusion. Serum troponin T levels, infarct size, cardiomyocyte apoptosis, reactive oxygen species (ROS) production, and infiltration of neutrophils were assessed 24 h after reperfusion, while the macrophage phenotypes, macrophage infiltration, and inflammatory cytokine levels were assessed 48 h after reperfusion. Results. Compared with the control group, the C15‐treated mice showed an obvious amelioration of I/R injury and displayed less ROS, accompanied by reduced neutrophil recruitment. C15 decreased the tumor necrosis factor‐ (TNF‐) α and interleukin‐ (IL‐) 6 levels and increased the IL‐10 levels in the serum of the I/R mice, which suggested a suppressed inflammatory response that could be related to elevated alternatively activated M2 macrophages with characteristic skewed expression of M2 markers and inhibition of classically activated M1 marker expression. Conclusion. C15 may induce alternatively activated M2 macrophage polarization and suppress the inflammatory response to protect against myocardial I/R injury in mice.
Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway
Authors: Tian Yikui , Piras Bryan A. , Kron Irving L. , French Brent A. , Yang Zequan
Published: June 2015

Background. Activation of the adenosineA2Breceptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying theA2BR-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated byA2BR.Methods and Results. C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selectiveA2BR antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selectiveA2BR agonist, significantly reduced myocardial infarct size, and its protective effect could be blocked by either ATL-801 or wortmannin. BAY 60-6583 increased phosphorylated Akt (p-Akt) levels in the heart at 10 min of reperfusion, and this phosphorylation could also be blocked by ATL-801 or wortmannin. Furthermore, BAY 60-6583 significantly increased M2 macrophages and decreased M1 macrophage and neutrophils infiltration in reperfused hearts, which also could be blocked by wortmannin. Meanwhile, confocal imaging studies showed that the majority of Akt phosphorylation in the heart was colocalized to CD206+ cells in both control and BAY 60-6583 pretreated hearts.Conclusion. Our results indicated that pretreatment with BAY 60-6583 protects the heart against myocardial IR injury by its anti-inflammatory effects, probably by modulating macrophages phenotype switching via a PI3K/Akt pathway.
Hydration Status Is Associated with Aortic Stiffness, but Not with Peripheral Arterial Stiffness, in Chronically Hemodialysed Patients
Authors: Bia Daniel , Galli Cintia , Valtuille Rodolfo , Zócalo Yanina , Wray Sandra A. , Armentano Ricardo L. , Cabrera Fischer Edmundo I.
Published: June 2015

Background. Adequate fluid management could be essential to minimize high arterial stiffness observed in chronically hemodialyzed patients (CHP).Aim. To determine the association between body fluid status and central and peripheral arterial stiffness levels.Methods. Arterial stiffness was assessed in 65 CHP by measuring the pulse wave velocity (PWV) in a central arterial pathway (carotid-femoral) and in a peripheral pathway (carotid-brachial). A blood pressure-independent regional arterial stiffness index was calculated using PWV. Volume status was assessed by whole-body multiple-frequency bioimpedance. Patients were first observed as an entire group and then divided into three different fluid status-related groups: normal, overhydration, and dehydration groups.Results. Only carotid-femoral stiffness was positively associated (P<0.05) with the hydration status evaluated through extracellular/intracellular fluid, extracellular/Total Body Fluid, and absolute and relative overhydration.Conclusion. Volume status and overload are associated with central, but not peripheral, arterial stiffness levels with independence of the blood pressure level, in CHP.
Effect of Friction Model and Tire Maneuvering on Tire-Pavement Contact Stress
Authors: Zhou Haichao , Wang Guolin , Ding Yangmin , Yang Jian , Liang Chen , Fu Jing
Published: June 2015

This paper aims to simulate the effects of different friction models on tire braking. A truck radial tire (295/80R22.5) was modeled and the model was validated with tire deflection. An exponential decay friction model that considers the effect of sliding velocity on friction coefficients was adopted for analyzing braking performance. The result shows that the exponential decay friction model used for evaluating braking ability meets design requirements of antilock braking system (ABS). The tire-pavement contact stress characteristics at various driving conditions (static, free rolling, braking, camber, and cornering) were analyzed. It is found that the change of driving conditions has direct influence on tire-pavement contact stress distribution. The results provide the guidance for tire braking performance evaluation.
Imaging-Duration Embedded Dynamic Scheduling of Earth Observation Satellites for Emergent Events
Authors: Niu Xiaonan , Tang Hong , Wu Lixin , Deng Run , Zhai Xuejun
Published: June 2015

We present novel two-stage dynamic scheduling of earth observation satellites to provide emergency response by making full use of the duration of the imaging task execution. In the first stage, the multiobjective genetic algorithm NSGA-II is used to produce an optimal satellite imaging schedule schema, which is robust to dynamic adjustment as possible emergent events occur in the future. In the second stage, when certain emergent events do occur, a dynamic adjusting heuristic algorithm (CTM-DAHA) is applied to arrange new tasks into the robust imaging schedule. Different from the existing dynamic scheduling methods, the imaging duration is embedded in the two stages to make full use of current satellite resources. In the stage of robust satellite scheduling, total task execution time is used as a robust indicator to obtain a satellite schedule with less imaging time. In other words, more imaging time is preserved for future emergent events. In the stage of dynamic adjustment, a compact task merging strategy is applied to combine both of existing tasks and emergency tasks into a composite task with least imaging time. Simulated experiments indicate that the proposed method can produce a more robust and effective satellite imaging schedule.
Alcohol and Substance Use in the Jewish Community: A Pilot Study
Authors: Baruch Melanie , Benarroch Abraham , Rockman Gary E.
Published: June 2015

Awareness of addictions in the Jewish community is becoming increasingly prevalent, and yet, a gap exists in the literature regarding addictions in this community. Knowledge about the prevalence of addictions within Jewish communities is limited; some believe that Jews cannot be affected by addictions. To address this gap, a pilot study was conducted to gather preliminary evidence relating to addictions and substance use in the Jewish community. Results indicate that a significant portion of the Jewish community knows someone affected by an addiction and that over 20% have a family history of addiction. Future research needs are discussed.
Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia‐Reperfusion in the Rat
Authors: Onal Ozkan , Yetisir Fahri , Sarer A. Ebru Salman , Zeybek N. Dilara , Onal C. Oztug , Yurekli Banu , Celik H. Tugrul , Sirma Ayse , Kılıc Mehmet
Published: June 2015

Objectives. Intestinal ischemia‐reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH‐Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH‐Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.
A Bidimensional System of Facial Movement Analysis Conception and Reliability in Adults
Authors: Baude Marjolaine , Hutin Emilie , Gracies Jean-Michel
Published: June 2015

Objective. To design a bidimensional facial movement measuring tool and study its reliability.Methods. We utilized the free video-analysis software Kinovea that can track preselected points during movements and measure two-point distances off-line. Three raters positioned facial markers on 10 healthy individuals and video-taped them during maximal bilateral contractions of frontalis, corrugator, orbicularis oculi, zygomaticus, orbicularis oris, and buccinator, on two occasions. Each rater also analyzed the first video twice, one week apart. For each muscle, intrarater reliability was measured by percent agreements (PA) and intraclass correlation coefficients (ICC) between two assessments of the same video one week apart and between assessments of two videos collected one week apart. Interrater reliability was measured by PA, ICC, and coefficients of variation (CV) between assessments of the first video-recording by the three raters.Results. Intrarater and interrater reliabilities were good to excellent for frontalis (PA and ICC > 70%; CV < 15%), moderate for orbicularis oculi, zygomaticus, and orbicularis oris, and poor for corrugator and buccinators.Discussion. Without formal prior training, the proposed method was reliable for frontalis in healthy subjects. Improved marker selection, training sessions, and testing reliability in patients with facial paresis may enhance reliability for orbicularis oculi, zygomaticus, and orbicularis oris.
Retinitis Pigmentosa withEYSMutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations
Authors: Arai Yuuki , Maeda Akiko , Hirami Yasuhiko , Ishigami Chie , Kosugi Shinji , Mandai Michiko , Kurimoto Yasuo , Takahashi Masayo
Published: June 2015

The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is,ABCA4for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic.EYSmutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two majorEYSmutations identified in this cohort.EYSmutations are the most prevalent among Japanese patients with IRD.
Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice
Authors: Jiang Ying , Zhou Zhen , Meng Qing-tao , Sun Qian , Su Wating , Lei Shaoqing , Xia Zhengyuan , Xia Zhong-yuan
Published: June 2015

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway.Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R.Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-)αbut decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-αand MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA.Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway.
Immunohistochemical Expression of CXCR4 on Breast Cancer and Its Clinical Significance
Authors: Okuyama Kishima Marina , Oliveira Carlos Eduardo Coral de , Banin-Hirata Bruna Karina , Losi-Guembarovski Roberta , Brajão de Oliveira Karen , Amarante Marla Karine , Watanabe Maria Angelica Ehara
Published: June 2015

Many tumor cells express chemokines and chemokine receptors, and, for this reason, these molecules can affect the tumor progression. It is known that breast cancer is a complex and heterogeneous neoplasia comprising distinct diseases, histological characteristics, and clinical outcomes. The most studied role for CXCL12 chemokine and its receptor CXCR4 in breast cancer pathogenesis is the metastasis event, although several reports have demonstrated its involvement in other processes, such as angiogenesis and tumor growth. It has been found that CXCR4 is required for breast cancer cell migration to other sites such as lung, bone, and lymph nodes, which express high levels of CXCL12 chemokine. Therefore, CXCR4 is being considered a prognostic marker in breast cancer. Within this context, this review summarizes established studies involving expression of CXCR4 on breast cancer, focusing on its clinical significance.
Human Tumor Antigens and Cancer Immunotherapy
Authors: Vigneron Nathalie
Published: June 2015

With the recent developments of adoptive T cell therapies and the use of new monoclonal antibodies against the immune checkpoints, immunotherapy is at a turning point. Key players for the success of these therapies are the cytolytic T lymphocytes, which are a subset of T cells able to recognize and kill tumor cells. Here, I review the nature of the antigenic peptides recognized by these T cells and the processes involved in their presentation. I discuss the importance of understanding how each antigenic peptide is processed in the context of immunotherapy and vaccine delivery.
Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer
Authors: Du Juan , Cieslak John A. , Welsh Jessemae L. , Sibenaller Zita A. , Allen Bryan G. , Wagner Brett A. , Kalen Amanda L. , Doskey Claire M. , Strother Robert K. , Button Anna M. , Mott Sarah L. , Smith Brian , Tsai Susan , Mezhir James , Goswami Prabhat C. , Spitz Douglas R. , Buettner Garry R. , Cullen Joseph J.
Published: June 2015

The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress–induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer. Cancer Res; 75(16); 3314–26. ©2015 AACR.
Measuring Vocal Function in Professional Music Theater Singers: Construct Validation of the Evaluation of the Ability to Sing Easily (EASE)
Authors: Phyland Debra J. , Pallant Julie F. , Thibeault Susan L. , Benninger Michael S. , Vallance Neil , Smith Julian A.
Published: June 2015

Overview: Working music theater singers (MTS) typically have a heavy vocal load and little is known about their perception of vocal function. The Evaluation of the Ability to Sing Easily (EASE) was used to assess professional MTS' perceptions of current singing voice status and to compare scores across demographic and performance characteristics and to evaluate the construct validity of the EASE and its subscales (VF = Vocal Fatigue, PRI = Pathologic-Risk Indicators). Methods: Professional MTS (n = 284) completed an online survey including the EASE and two additional Vocal Concern (VC) items. Scores were compared across age, gender, whether currently working, role, perceived vocal load over the past 24 h and self-reported voice problem. Results: For the whole cohort, statistically significant differences were found on all subscales according to whether or not singers perceived themselves to have a voice problem (p < 0.001). Currently performing singers were significantly different from those not performing in a show on the EASE Total (p = 0.014) and VF (p = 0.002), but not for PRI and VC. In the currently performing singer group, significant differences were found for gender, role and perceived voice problem on the EASE Total and all subscales (p < 0.01). Significantly higher VF scores were recorded for singers with heavy vocal load (p = 0.01), but there were no differences on the EASE Total (p = 0.57), PRI (p = 0.19) or VC subscales (p = 0.53). Among these performing singers, no significant age differences were found for any EASE subscales. Conclusions: These findings provide further validation of the EASE as a useful tool for measuring singers' perceptions of vocal function and suggest that the subscales should be scored separately. Future evaluation of the EASE against objective clinical assessments (e.g., videostroboscopy) is recommended. © 2014 S. Karger AG, Basel
Phase I Trial of Sorafenib Following Liver Transplantation in Patients with High-Risk Hepatocellular Carcinoma
Authors: Siegel Abby B. , El-Khoueiry Anthony B. , Finn Richard S. , Guthrie Katherine A. , Goyal Abhishek , Venook Alan P. , Blanke Charles D. , Verna Elizabeth C. , Dove Lorna , Emond Jean , Kato Tomoaki , Samstein Benjamin , Busuttil Ronald , Remotti Helen , Coffey Amy , Brown Jr Robert S.
Published: June 2015

Liver transplantation offers excellent long-term survival for hepatocellular carcinoma (HCC) patients who fall within established criteria. For those outside such criteria, or with high-risk pathologic features in the explant, HCC recurrence rates are higher. We conducted a multicenter phase I trial of sorafenib in liver transplantation patients with high-risk HCC. Subjects had HCC outside the Milan criteria (pre- or post-transplant), poorly differentiated tumors, or vascular invasion. We used a standard 3+3 phase I design with a planned duration of treatment of 24 weeks. Correlative studies included the number of circulating endothelial cells (CECs), plasma biomarkers, and tumor expression of p-Erk, p-Akt, and c-Met in tissue micro-arrays. We enrolled 14 patients with a median age of 63 years. Of these, 93% were men and 71% had underlying hepatitis C virus (HCV) and 21% had HBV. The maximum tolerated dose of sorafenib was 200 mg BID. Grade 3-4 toxicities seen in >10% of subjects included leukopenia (21%), elevated gamma-glutamyl transferase (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 953 days, one patient died and four recurred. The mean CEC number at baseline was 21 cells/4 ml for those who recurred, and 80 cells/4 ml for those who did not (p=0.10). Mean soluble vascular endothelial growth factor receptor-2 levels decreased after 1 month on sorafenib (p=0.09), but did not correlate with recurrence. There was a trend for tumor c-Met expression to correlate with increased risk of recurrence. Post-transplant sorafenib was found to be feasible and tolerable at 200 mg PO BID. The effect of post-transplant sorafenib on recurrence-free survival is potentially promising but needs further validation in a larger study.
Tumor Markers for Hepatocellular Carcinoma: Simple and Significant Predictors of Outcome in Patients with HCC
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Sone Yasuhiro , Kaneoka Yuji , Maeda Atsuyuki
Published: June 2015

Background: The effectiveness of tumor markers in evaluating outcomes of patients with hepatocellular carcinoma (HCC) remains to be clarified. Summary: The usefulness of the HCC tumor markers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), and des-gamma-carboxy prothrombin (DCP) was reviewed. Elevations in these tumor markers at the time of HCC diagnosis correlate with disease progression as assessed by both imaging studies and pathologic examinations. The combination of these three tumor markers results in good predictive ability for patient survival after diagnosis. In addition, combination at the time of HCC diagnosis of these three tumor markers (as a measure of tumor progression) and serum albumin and bilirubin levels (as indicators of remnant liver function) can be used for HCC staging and further predicts prognosis in patients with HCC. Key Message: The prognosis of patients with HCC can be well discriminated based solely on serum markers. Staging of HCC with serum markers is objective; if stored serum samples are available, HCC stages can be standardized across different countries and time periods.
Regional Variation of Chronic Kidney Disease in Germany: Results From Two Population-Based Surveys
Authors: Aumann Nicole , Baumeister Sebastian E. , Rettig Rainer , Lieb Wolfgang , Werner André , Döring Angela , Peters Annette , Koenig Wolfgang , Hannemann Anke , Wallaschofski Henri , Nauck Matthias , Stracke Sylvia , Völzke Henry , Meisinger Christa
Published: June 2015

Background/Aims: Due to the increasing prevalence of risk factors for chronic kidney disease (CKD), kidney dysfunction becomes a major public health problem. We investigated the CKD prevalence and determined to what extent the variation of risk factors explains the different CKD prevalence in Germany. Methods: We analyzed data from 6,054 participants, aged 31 to 82 years, from the Study of Health in Pomerania (SHIP-1) in Northeast Germany and the Cooperative Health Research in the Region of Augsburg (KORA F4) Study in Southern Germany. Regional differences in selected percentiles corresponding to the cutpoints for estimated glomerular filtration rate (eGFR, <60 ml/min per 1.73 m2) and albumin-to-creatinine ratio (ACR, ≥30 mg/g) were tested using quantile regression models that adjusted for CKD risk factors. Results: The prevalence of decreased eGFRcreatinine-cystatinC (5.9 vs. 3.1 %, p <0.001) and albuminuria (20.2 vs. 8.8 %, p<0.001) were higher in SHIP-1 than in KORA F4. The differential distribution of risk factors explained 18-21% of the regional differences of decreased eGFRcreatinine-cystatinC and high ACR. Conclusions: The CKD prevalence is higher in Northeast than in Southern Germany. Differences in the prevalence of risk factors partly explain the higher disease burden of CKD in Northeast than in Southern Germany.
The Missing Link - Likely Pathogenetic Role of GM3 and Other Gangliosides in the Development of Diabetic Nephropathy
Authors: Vukovic Igor , Bozic Josko , Markotic Anita , Ljubicic Srecko , Ticinovic Kurir Tina
Published: June 2015

Despite scientific advances, diabetic nephropathy remains both a therapeutical challenge, and one of the major diabetic complications. Chemical structure of gangliosides, the most complex of glycosphingolipids, is characterised by one or more sialic acids and carbohydrate groups linked to a ceramide structure. Their potential pathogenetic role in a number of disorders linked to diabetes mellitus has recently been conjectured, due to evidence of their negative modulation of the insulin-mediated signaling and general effects on key cell functions like proliferation, differentiation, apoptosis, cellular signaling and adhesion. Elevated levels of advanced glycation products (AGE) usually found in diabetic conditions seem to be responsible for increased concentration of a-series gangliosides in tissues, most notably GM3. GM3 was shown to compromise the renal pericyte and mesangial cell regeneration via the inactivation of VEGF receptor and the receptor-associated Akt signaling pathway. Likewise, the lipid raft theory opened a new research area for GM3 influence, since in the glycosynapse model glycosphingolipids have a key cell-to-cell communication unit with modulating capabilities on signaling receptors. The goal of this review is to provide insight into currently available theories on proposed mechanisms that mark the GM3 as a pathophysiological mediator in the development of diabetic nephropathy.
The Anticancer Activity of the Substituted Pyridone-Annelated Isoindigo (5'-Cl) Involves G0/G1 Cell Cycle Arrest and Inactivation of CDKs in the Promyelocytic Leukemia Cell Line HL-60
Authors: Saleh Ayman M. , Aljada Ahmad , El-Abadelah Mustafa M. , Taha Mutasem O. , Sabri Salim S. , Zahra Jalal A. , Aziz Mohammad Azhar
Published: June 2015

Background/Aims: The antileukemic potential of isoindigos make them desired candidates for understanding their mechanism of action. We have recently synthesized a novel group of pyridone-annelated isoindigos and identified the derivative 5'-Cl that is cytotoxic to various cancer cell lines. In the present study, we analyzed the effect of this compound on cell cycle of the promyelocytic leukemia cell line HL-60. Methods: HL-60 cells were treated with 5'-Cl and its effect on cell cycle stages were determined by flow cytometry. Expression of cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) were determined by Western blotting, and activation of CDKs was studied using kinase assays. Results: 5'-Cl remarkably arrested cell cycle in HL-60 cells at the G0/G1 phase in a dose and time-dependent manner. Furthermore, 5'-Cl treatment significantly inhibited expression of D-cyclins, CDK2 and CDK4 and suppressed phosphorylation of the retinoblastoma protein Rb, whereas it increased the level of CKI p21. Molecular modelling experiments show that 5'-Cl may compete with ATP for binding to the catalytic subunit of CDK2 and CDK4 that could lead to inhibition of these enzymes. Indeed, 5'-Cl inhibited the kinase activity of CDK2 and CDK4 both in cell free systems and in treated cells. 5'-Cl also inhibited cell cycle progression in several other tumor cell lines. Conclusion: We demonstrate the potent inhibitory effects of 5'-Cl on HL-60 cells could be mediated by arresting cells in the G0/G1 phase.
Restoration of Epigenetically Silenced Sulfatase 1 Expression by 5-Aza-2′-Deoxycytidine Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy-Induced Apoptosis
Authors: Shire Abdirashid , Lomberk Gwen , Lai Jin-Ping , Zou Hongzhi , Tsuchiya Norihiko , Aderca Ileana , Moser Catherine D. , Gulaid Kadra H. , Oseini Abdul , Hu Chunling , Warsame Omar , Jenkins Robert B. , Roberts Lewis R.
Published: June 2015

Background: Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer death worldwide. Sulfatase 1 (SULF1) functions as a tumor suppressor in HCC cell lines in vitro but also has an oncogenic effect in some HCCs in vivo. Aim: The purpose of this study was to examine the mechanisms regulating SULF1 and its function in HCC. Methods: First, SULF1 mRNA and protein expression were examined. Second, we examined SULF1 gene copy numbers in HCC cells. Third, we assessed whether DNA methylation or methylation and/or acetylation of histone marks on the promoter regulate SULF1 expression. Finally, we examined the effect of 5-aza-2′-deoxycytidine (5-Aza-dC) on sulfatase activity and drug-induced apoptosis. Results: SULF1 mRNA was downregulated in nine of eleven HCC cell lines, but only in six of ten primary tumors. SULF1 mRNA correlated with protein expression. Gene copy number assessment by fluorescence in situ hybridization showed intact SULF1 alleles in low-SULF1-expressing cell lines. CpG island methylation in the SULF1 promoter and two downstream CpG islands did not show an inverse correlation between DNA methylation and SULF1 expression. However, chromatin immunoprecipitation showed that the SULF1 promoter acquires a silenced chromatin state in low-SULF1-expressing cells through an increase in di/trimethyl-K9H3 and trimethyl-K27H3 and a concomitant loss of activating acetyl K9, K14H3 marks. 5-Aza-dC restored SULF1 mRNA expression in SULF1-negative cell lines, with an associated increase in sulfatase activity and sensitization of HCC cells to cisplatin-induced apoptosis. Conclusion: SULF1 gene silencing in HCC occurs through histone modifications on the SULF1 promoter. Restoration of SULF1 mRNA expression by 5-Aza-dC sensitized HCC cells to drug-induced apoptosis.
Ethics in Animal-Based Research
Authors: Gross Dominik , Tolba René H.
Published: June 2015

In recent years, there have been a number of new demands and regulations which have reignited the discussion on ethics in animal-based research. In the light of this development, the present review first presents an overview of underlying core ethical questions and issues. This is followed by an outline of the current discussion on whether animals (used for experimentation) should have rights ascribed to them and whether animals need to have certain characteristics in order to be the beneficiaries of rights. The discourse on concepts of sentience and the ‘sociozoological scale' in particular is mapped out in this regard. There follows an outline of relevant ethical positions and current moral approaches to animal-based research (animal rights position, utilitarianism, ‘convergence position', intrinsic cultural value of fundamental research, ‘contractarianism', anthropocentrism, principle of the three Rs).
Stroke Knowledge in Spanish-Speaking Populations
Authors: Hawkes Maximiliano A. , Ameriso Sebastián F. , Willey Joshua Z.
Published: June 2015

Background: Spanish is the second most-spoken language in the world. Spanish-speaking populations (SSP) have heterogeneous cultural backgrounds, racial and ethnical origins, economic status, and access to health care systems. There are no published reviews about stroke knowledge in SSP. We reviewed the existing literature addressing stroke knowledge among SSP and propose here some future directions for research. Summary: We identified 18 suitable studies by searching PubMed, Lilacs, Scopus, Embase, Cochrane and Scielo databases, and by looking at reference lists of eligible articles. We also included 2 conference abstracts. Data related to stroke knowledge from studies of Spanish-speakers were analyzed. Key Messages: Little is known about stroke knowledge in SSP, especially in Latin America. Information is lacking even among subjects at risk, stroke patients, stroke survivors, and health care providers. ‘Ictus', the word used for stroke in Spanish, is largely unrecognized among subjects at risk. Furthermore, access to medical care and the availability of neurologists are suboptimal in many regions. There are several potential issues to solve regarding stroke knowledge and stroke care in SSP. Programs to educate the general population and non-neurologists medical providers in stroke and telemedicine may be better ways of improving the present situation.
Dyschromatosis Universalis Hereditaria with Renal Failure
Authors: Rojhirunsakool Salinee , Vachiramon Vasanop
Published: June 2015

Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant inherited dermatosis which usually appears during childhood and is characterized by dyspigmentation, with both hypopigmented and hyperpigmented macules. We report a case of DUH with unexplained childhood-onset renal failure. The association between DUH and renal failure is yet to be proven by further studies.
Case Report of Sump Syndrome after Laser Conjunctivodacryocystorhinostomy
Authors: Goel Ruchi , Kishore Divya , Kumar Sushil , Agarwal Tushar , Nagpal Smriti , Apoorva A.G.
Published: June 2015

The sump syndrome was initially described in relation to patients who had undergone external dacryocystorhinostomy. Here we report a case of sump syndrome that developed following laser conjunctivodacryocystorhinostomy (CDCR) due to tube displacement after a bout of forceful sneezing. Unlike cases of external dacryocystorhinostomy where flaps are sutured, there is a potential space created by the sac remnants in laser CDCR. Hence, any displacement of the tube will lead to the improper drainage of secretions with superadded infections of the contents (as occurred in this case). Therefore, in laser CDCR, it is imperative to create an appropriately placed osteotomy with a correctly sized tube that is well secured to avoid displacement along with patient education regarding tube care.
Spontaneous Intracranial Hypotension Manifesting as a Unilateral Subdural Hematoma with a Marked Midline Shift
Authors: Inamasu Joji , Moriya Shigeta , Shibata Junpei , Kumai Tadashi , Hirose Yuichi
Published: June 2015

Spontaneous intracranial hypotension (SIH) is a syndrome in which hypovolemia of the cerebrospinal fluid (CSF) results in various symptoms. Although its prognosis is usually benign, cases with a rapid neurologic deterioration resulting in an altered mental status have been reported. One of the characteristic radiographic findings in such cases is the presence of bilateral accumulation of subdural fluid (hematoma/hygroma). When SIH-related subdural hematoma is present only unilaterally with a concomitant midline shift, making an accurate diagnosis may be challenging, and inadvertent hematoma evacuation may result in further neurologic deterioration. We report a 58-year-old woman with an altered mental status who had visited a local hospital and in whom a brain CT showed a unilateral subdural hematoma with a marked midline shift. She was referred to our department because of her neurologic deterioration after hematoma evacuation. A CT myelography revealed a massive CSF leakage in the entire thoracic epidural space. She made a full neurologic recovery following blood patch therapy. Our case is unique and educational because the suspicion for SIH as an underlying cause of subdural hematoma is warranted in nongeriatric patients not only with bilateral but also unilateral lesions. An immediate search for CSF leakage may be important in cases with failed hematoma evacuation surgery.
Development of Late-Onset Preeclampsia in Association with Road Densities as a Proxy for Traffic-Related Air Pollution
Authors: Wu Meng , Ries Jean-Jacques , Proietti Elena , Vogt Deborah , Hahn Sinuhe , Hoesli Irene
Published: June 2015

Introduction: Previous epidemiological studies indicate an association between maternal exposure to air pollution and an increased risk of hypertensive disorders in pregnancy. We analyzed the association between the occurrence of mild/severe and early-/late-onset preeclampsia (PE) and traffic-related air pollution (TRAP). Materials and Methods: Based on retrospective data, 50 pregnant women with PE were selected and matched with a control group of healthy pregnant women according to their age, parity, and number of fetuses. The total length of major roads around the women's home within a radius of 100, 200, 300, and 500 m and the distances from the domicile to the nearest ‘first class' main road and freeway were used as a proxy indicator of TRAP. We compared a PE subgroup and control group in terms of their exposure to TRAP. Results: Late-onset PE cases showed a significantly higher occurrence with density of major roads within a radius of 100-300 m compared to early onset cases (p = 0.006; 0.02; 0.04). In addition, a significantly shorter distance to the nearest ‘first class' main road was observed in late-onset PE cases (p = 0.0078). Conclusions: Exposure to TRAP during pregnancy was associated with an increased risk for the development of late-onset PE.