bluuebunny/crossref_metadata_2025 huggingface dataset:
Folated Synperonic-Cholesteryl Hemisuccinate Polymeric Micelles for the Targeted Delivery of Docetaxel in Melanoma
Authors: Varshosaz Jaleh , Taymouri Somayeh , Hassanzadeh Farshid , Haghjooy Javanmard Shaghayegh , Rostami Mahboobeh
Published: March 2015

The objective of this study was the synthesis of folic acid- (FA-) targeted polymeric micelles of Synperonic PE/F 127-cholesteryl hemisuccinate (PF127-Chol) for specific delivery of docetaxel (DTX). Targeted or nontargeted micelles loaded with DTX were prepared via dialysis method. The effects of processing variables on the physicochemical properties of targeted micelles were evaluated using a full factorial design. After the optimization of the polymer/drug ratio, the organic solvent type used for the preparation of the micelles, and the temperature of dialyzing medium, thein vitrocytotoxicity and cellular uptake of the optimized micelles were studied on B16F10 melanoma cells by flow cytometry and fluorescent microscopy. The anticancer efficacy of DTX-loaded FA-PF127-Chol was evaluated in mice bearing melanoma tumor. Optimized targeted micelles had the particle size of 171.3 nm, zeta potential of −7.8 mV, PDI of 0.325, and a high encapsulation efficiency that released the drug within 144 h. The MTT assay indicated that targeted micelles carrying DTX were significantly more cytotoxic, had higher cellular uptake, and reduced the tumor volume significantly more than the nontargeted micelles and the free drug. FA-PF127-Chol could be, therefore, a promising biomaterial for tumors overexpressing folate receptors.
Distributed Data Clustering via Opinion Dynamics
Authors: Oliva Gabriele , La Manna Damiano , Fagiolini Adriano , Setola Roberto
Published: March 2015

We provide a distributed method to partition a large set of data in clusters, characterized by small in-group and large out-group distances. We assume a wireless sensors network in which each sensor is given a large set of data and the objective is to provide a way to group the sensors in homogeneous clusters by information type. In previous literature, the desired number of clusters must be specified a priori by the user. In our approach, the clusters are constrained to have centroids with a distance at least ε between them and the number of desired clusters is not specified. Although traditional algorithms fail to solve the problem with this constraint, it can help obtain a better clustering. In this paper, a solution based on the Hegselmann-Krause opinion dynamics model is proposed to find an admissible, although suboptimal, solution. The Hegselmann-Krause model is a centralized algorithm; here we provide a distributed implementation, based on a combination of distributed consensus algorithms. A comparison with k-means algorithm concludes the paper.
Influence of Filler from a Renewable Resource and Silane Coupling Agent on the Properties of Epoxidized Natural Rubber Vulcanizates
Authors: Pongdong Wiphawadee , Nakason Charoen , Kummerlöwe Claudia , Vennemann Norbert
Published: March 2015

Rice husk ash (RHA) was used as a reinforcing filler in epoxidized natural rubber (ENR) with various loading levels (0, 10, 20, and 30 phr), and silica filled ENR was also studied for comparison. The effects of RHA content on cure characteristics, mechanical properties, dynamic mechanical properties, and thermoelastic behavior of the filled ENR composites were investigated. It was found that the incorporation of RHA significantly affected the cure characteristics and mechanical properties. That is, the incorporation of RHA caused faster curing reactions and increased Young’s modulus and tensile strength relative to the unfilled compound. This might be attributed to the metal oxide impurities in RHA that enhance the crosslinking reactions, thus increasing the crosslink density. Further improvements in the curing behavior and the mechanical properties of the filled composites were achieved byin situsilanization with bis(triethoxysilylpropyl) tetrasulfide (Si69). It was found that the rubber-filler interactions reinforced the composites. This was indicated by the decreased damping characteristic(tan ⁡δ)and the other changes in the mechanical properties. Furthermore, the ENR composites with Si69 had improved filler dispersion. Temperature scanning stress relaxation (TSSR) results suggest that the metal oxide impurities in RHA promote degradation of the polymer network at elevated temperatures.
Theoretical and Numerical Studies of Dynamic Scaling of a Six-Degree-of-Freedom Laser Propulsion Vehicle
Authors: Takahashi Masayuki , Ohnishi Naofumi
Published: March 2015

To estimate the flight reactions of a full-scale vehicle from reduced-scale tests, we constructed a scaling theory for the vehicle size, input energy, moment of inertia, and pulse frequency needed to maintain dynamic equivalence between a laboratory-scale and full-scale launch of a laser propulsion vehicle. The dynamic scaling law for a single pulse was constructed using translational and angular equations of motion. The analytical scaling was confirmed for a single-pulse incident using a fluid-orbit coupling simulator for the interaction between the blast wave and the vehicle. Motion equivalence was maintained for multiple pulses by adjusting the repetition frequency of the pulse incident to correct for the effect of aerodynamic drag during the free flight of the pulse-to-pulse interval. The flight of a full-scale vehicle can be estimated for single- and multiple-pulse operations from the flight data for a small-scale vehicle using the proposed scaling theory, which provides correlations between the characteristics of small-scale and large-scale flight systems. Small-scale tests were shown to be useful in estimating the flight of a full-scale vehicle using dynamic scaling theory.
Chemical Composition and Antioxidant and Antimicrobial Activities of Wormwood (Artemisia absinthiumL.) Essential Oils and Phenolics
Authors: Msaada Kamel , Salem Nidhal , Bachrouch Olfa , Bousselmi Slim , Tammar Sonia , Alfaify Abdulkhaleg , Al Sane Khaldoun , Ben Ammar Wided , Azeiz Sana , Haj Brahim Adel , Hammami Majdi , Selmi Sawsen , Limam Ferid , Marzouk Brahim
Published: March 2015

The aim of this study was to determine the chemical variability of wormwood extracts as affected by the growing region. Antioxidant and antimicrobial activities were also investigated. The essential oil composition variability ofA. absinthiumL. aerial parts collected from four different Tunisian regions was assessed by gas chromatography (GC/FID) and by gas chromatography mass spectrometry (GC/MS). In addition, total polyphenols, flavonoids, and condensed tannins as well as antioxidant, antibacterial, and antifungal activities of methanolic extract and essential oils were undertaken. Chromatographic analysis of wormwood essential oils showed the predominance of monoterpene hydrocarbons represented mainly by chamazulene. RP-HPLC analysis of wormwood methanolic extract revealed the predominance of phenolic acids. Antiradical activity was region-dependant and the methanolic extract of Bou Salem region has the strongest activity (CI50=9.38±0.82 µg/mL). Concerning the reducing power, the methanolic extract of Bou Salem, Jérissa, and Boukornine regions was more active than the positive control. Obtained results of antimicrobial activities showed that wormwood essential oil is endowed with important antibacterial activity which was strongly related to the organoleptic quality of oil which appeared strongly region-dependant.A. absinthiumL. EOs investigated are quite interesting from a pharmaceutical standpoint because of their biological activities.
Neutron Scattering on Impurity Nanoclusters in Gel Samples
Authors: Efimov V. B. , Mezhov-Deglin L. P. , Dewhurst C. D. , Lokhov A. V. , Nesvizhevsky V. V.
Published: March 2015

Results of recent SANS experiments with impurity-helium gel (IHG) samples in He-II are presented. We estimate the mean size of the impurity nanoparticles that form the frame of the IHG samples and discuss the possibility to use IHG samples for the production of ultracold neutrons (UCNs) in He-II cooled to the temperature of a few mK, as well as the reflection of UCNs at any temperature. Our results indicate that the most promising materials for these purposes might be the heavy water gel samples with the mean sizes of D2O clusters ofd~8 nm and the heavy alcohol gel samples with the mean sizes of clusters ofd~15 nm.
Stability-Indicating HPLC Determination of Gemcitabine in Pharmaceutical Formulations
Authors: Singh Rahul , Shakya Ashok K. , Naik Rajashri , Shalan Naeem
Published: March 2015

A simple, sensitive, inexpensive, and rapid stability indicating high performance liquid chromatographic method has been developed for determination of gemcitabine in injectable dosage forms using theophylline as internal standard. Chromatographic separation was achieved on a Phenomenex Luna C-18 column (250 mm × 4.6 mm; 5μ) with a mobile phase consisting of 90% water and 10% acetonitrile (pH7.00±0.05). The signals of gemcitabine and theophylline were recorded at 275 nm. Calibration curves were linear in the concentration range of 0.5–50 μg/mL. The correlation coefficient was 0.999 or higher. The limit of detection and limit of quantitation were 0.1498 and 0.4541 μg/mL, respectively. The inter- and intraday precision were less than 2%. Accuracy of the method ranged from 100.2% to 100.4%. Stability studies indicate that the drug was stable to sunlight and UV light. The drug gives 6 different hydrolytic products under alkaline stress and 3 in acidic condition. Aqueous and oxidative stress conditions also degrade the drug. Degradation was higher in the alkaline condition compared to other stress conditions. The robustness of the methods was evaluated using design of experiments. Validation reveals that the proposed method is specific, accurate, precise, reliable, robust, reproducible, and suitable for the quantitative analysis.
Synthesis and Characterization of Biodegradable Polyurethane for Hypopharyngeal Tissue Engineering
Authors: Shen Zhisen , Lu Dakai , Li Qun , Zhang Zongyong , Zhu Yabin
Published: March 2015

Biodegradable crosslinked polyurethane (cPU) was synthesized using polyethylene glycol (PEG), L-lactide (L-LA), and hexamethylene diisocyanate (HDI), with iron acetylacetonate (Fe(acac)3) as the catalyst and PEG as the extender. Chemical components of the obtained polymers were characterized by FTIR spectroscopy,1H NMR spectra, and Gel Permeation Chromatography (GPC). The thermodynamic properties, mechanical behaviors, surface hydrophilicity, degradability, and cytotoxicity were tested via differential scanning calorimetry (DSC), tensile tests, contact angle measurements, and cell culture. The results show that the synthesized cPU possessed good flexibility with quite low glass transition temperature (Tg, −22°C) and good wettability. Water uptake measured as high as 229.7 ± 18.7%. These properties make cPU a good candidate material for engineering soft tissues such as the hypopharynx.In vitroandin vivotests showed that cPU has the ability to support the growth of human hypopharyngeal fibroblasts and angiogenesis was observed around cPU after it was implanted subcutaneously in SD rats.
Virus-Associated Hemophagocytic Syndrome in Renal Transplant Recipients: Report of 2 Cases from a Single Center
Authors: Nanmoku Koji , Yamamoto Takayuki , Tsujita Makoto , Hiramitsu Takahisa , Goto Norihiko , Katayama Akio , Narumi Shunji , Watarai Yoshihiko , Kobayashi Takaaki , Uchida Kazuharu
Published: March 2015

Virus-associated hemophagocytic syndrome (HPS) is a potentially fatal complication of immunosuppression for transplantation. However, it presents with heterogeneous clinical symptoms (fever, disturbed consciousness, and hepatosplenomegaly) and laboratory findings (pancytopenia, elevated hepatic enzyme levels, abnormal coagulation, and hyperferritinemia), impeding diagnosis. Case 1: A 39-year-old female developed fever 4 years after ABO-incompatible living-related renal transplantation. Laboratory findings revealed thrombocytopenia, elevated hepatic enzymes, Epstein-Barr virus (EBV) DNA seropositivity, and hyperferritinemia. EBV-associated HPS was confirmed by bone marrow aspiration. Steroid pulse therapy and etoposide were ineffective. Disseminated intravascular coagulation resulted in multiple organ failure, and the patient died 32 days after disease onset. Case 2: A 67-year-old male was admitted with rotavirus enteritis a month after living-unrelated renal transplantation. He developed sudden-onset high fever, disturbance of consciousness, and tachypnea 8 days after admission. Laboratory findings revealed elevated hepatic enzyme levels, hyperkalemia, and hyperferritinemia. Emergency continuous hemodiafiltration ameliorated the fever, and steroid pulse therapy improved abnormal laboratory values. Varicella-zoster virus meningitis was confirmed by spinal tap. Acyclovir improved consciousness, and he was discharged 87 days after admission. Fatal virus-associated HPS may develop in organ transplant patients receiving immunosuppressive therapy. Pathognomonic hyperferritinemia is useful for differential diagnosis.
p40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations: A Comparative Immunohistochemical Study with 34betaE12
Authors: Brustmann Hermann
Published: March 2015

Immunohistochemistry is important for the accurate diagnosis of basal cells in atypical glandular proliferations of the prostate. p40, an isoform of p63, may be an adjunct to a marker panel in this setting. Biopsies of 68 patients were analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal cell staining was classified as negative, partial (<60%), or diffuse (≥60%); irregular staining was defined as discordant staining patterns. In acinar proliferations (N=41), partial staining for both markers was seen in 42%, and diffuse staining in 46% of reactive cases. An irregular reactivity was noted in one case only (2%). Finally, these lesions were signed out as benign. Acinar proliferations negative for both markers and limited amount of glands (≤4) were termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two cases showed partial, three cases showed diffuse reactivity for both markers, and one case was stained irregular. All cases diagnosed as prostate carcinomas (N=20) had no evidence of basal cell staining for neither of the markers. p40 expression is closely correlated to 34betaE12 with respect to demonstration of basal cells of prostate glands and may provide further information on the dignity of glandular proliferations of the prostate.
Enterovesical Fistula Caused by a Toothpick
Authors: Tombolini Flavia , Lacetera Vito , Muzzonigro Giovanni
Published: March 2015

We present a case of enterovesical fistula caused by an accidental ingestion of a foreign body. A 23-year-old man presented to our hospital with pneumaturia, fecaluria, and abdominal pain but no recent possible causes of enterovesical fistula at anamnesis. Cystoscopy, cystography, and also colonoscopy were not able to detect the fistulous tract. Computer tomography (CT) revealed a fistula between bladder and bowels caused by a toothpick accidentally swallowed 2 years earlier. We tried to remove the foreign body endoscopically by cystoscopy and colonoscopy but with no success. The failure of endoscopic procedures required a surgical treatment. The patient underwent laparoscopic segmental resection of the sigmoid colon to remove the fistulous tract and the foreign body. The cystography revealed no external leakage of contrast from the bladder with complete resolution of the problem.
Global Dynamics of Avian Influenza Epidemic Models with Psychological Effect
Authors: Liu Sanhong , Pang Liuyong , Ruan Shigui , Zhang Xinan
Published: March 2015

Cross-sectional surveys conducted in Thailand and China after the outbreaks of the avian influenza A H5N1 and H7N9 viruses show a high degree of awareness of human avian influenza in both urban and rural populations, a higher level of proper hygienic practice among urban residents, and in particular a dramatically reduced number of visits to live markets in urban population after the influenza A H7N9 outbreak in China in 2013. In this paper, taking into account the psychological effect toward avian influenza in the human population, a bird-to-human transmission model in which the avian population exhibits saturation effect is constructed. The dynamical behavior of the model is studied by using the basic reproduction number. The results demonstrate that the saturation effect within avian population and the psychological effect in human population cannot change the stability of equilibria but can affect the number of infected humans if the disease is prevalent. Numerical simulations are given to support the theoretical results and sensitivity analyses of the basic reproduction number in terms of model parameters that are performed to seek for effective control measures for avian influenza.
A New Metabolism-Related Index Correlates with the Degree of Liver Fibrosis in Hepatitis C Virus-Positive Patients
Authors: Enomoto Hirayuki , Aizawa Nobuhiro , Nakamura Hideji , Takata Ryo , Sakai Yoshiyuki , Iwata Yoshinori , Tanaka Hironori , Ikeda Naoto , Aoki Tomoko , Hasegawa Kunihiro , Yoh Kazunori , Hashimoto Kenji , Ishii Akio , Takashima Tomoyuki , Saito Masaki , Imanishi Hiroyasu , Iijima Hiroko , Nishiguchi Shuhei
Published: March 2015

Background. Only a few biomarkers based on metabolic parameters for evaluating liver fibrosis have been reported. The aim of this study was to investigate the relevance of an index obtained from three metabolic variables (glycated albumin: GA, glycated hemoglobin: HbA1c, and branched-chain amino acids to tyrosine ratio: BTR) to the degree of liver fibrosis in hepatitis C virus virus- (HCV-) positive patients.Methods. A total of 394 HCV-positive patients were assessed based on the values of a new index (GA/HbA1c/BTR). The index findings were used to investigate the relationship with the degree of liver fibrosis.Results. The new index showed an association with the stage of fibrosis (METAVIR scores: F0-1: 0.42 ± 0.10, F2: 0.48 ± 0.15, F3: 0.56 ± 0.22, and F4: 0.71 ± 0.30). The index was negatively correlated with three variables of liver function: the prothrombin time percentage (P<0.0001), albumin level (P<0.0001), and cholinesterase level (P<0.0001). The new index showed a higher correlation related to liver function than FIB-4 and the APRI did. In addition, the index showed a higher AUROC value than that of FIB-4 and the APRI for prediction of liver cirrhosis.Conclusion. The new metabolism-related index, GA/HbA1c/BTR value, is shown to relate to the degree of liver fibrosis in HCV-positive patients.
Effect of Graphene and Fullerene Nanofillers on Controlling the Pore Size and Physicochemical Properties of Chitosan Nanocomposite Mesoporous Membranes
Authors: Fahim Irene S. , Marei Narguess , Salem Hanadi G. , Mamdouh Wael
Published: March 2015

Chitosan (CS) nanocomposite mesoporous membranes were fabricated by mixing CS with graphene (G) and fullerene (F) nanofillers, and the diffusion properties through CS membranes were studied. In addition, in order to enhance the binding between the internal CS chains, physical cross‐linking of CS by sodium tripolyphosphate (TPP) was carried out. F and G with different weight percentages (0.1, 0.5, and 1 wt.%) were added on physically cross‐linked chitosan (CLCS) and non‐cross‐linked chitosan (NCLCS) membranes by wet mixing. Permeability and diffusion time of CLCS and NCLCS membranes at different temperatures were investigated. The results revealed that the pore size of all fabricated CS membranes is in the mesoporous range (i.e., 2–50 nm). Moreover, the addition of G and F nanofillers to CLCS and NCLCS solutions aided in controlling the CS membranes’ pore size and was found to enhance the barrier effect of the CS membranes either by blocking the internal pores or decreasing the pore size. These results illustrate the significant possibility of controlling the pore size of CS membranes by cross‐linking and more importantly the careful selection of nanofillers and their percentage within the CS membranes. Controlling the pore size of CS membranes is a fundamental factor in packaging applications and membrane technology.
BATF2 Deficiency Promotes Progression in Human Colorectal Cancer via Activation of HGF/MET Signaling: A Potential Rationale for Combining MET Inhibitors with IFNs
Authors: Liu Zebing , Wei Ping , Yang Yu , Cui Wenli , Cao Bing , Tan Cong , Yu Baohua , Bi Rui , Xia Kaiqin , Chen Weixiang , Wang Yiqin , Zhang Youyuan , Du Xiang , Zhou Xiaoyan
Published: March 2015

Purpose: BATF2, a novel IFN-stimulated gene, inhibits tumor cell proliferation, invasion, and migration. The objectives of this study were to determine how BATF2 expression is associated with colorectal cancer progression and patient outcome, to investigate how BATF2 overexpression inhibits hepatocyte growth factor (HGF)/MET signaling, and to elucidate the rationale for combining MET inhibitors with IFN.

Experimental Design: BATF2 expression in colorectal cancer tissues was determined and correlated with colorectal cancer patient prognosis. Cultured colorectal cancer cells were used to investigate the effects of BATF2 overexpression on the malignant phenotype of colorectal cancer cells and HGF/MET signaling. Tumor xenograft models were used to validate the effects of BATF2 on colorectal cancer xenograft growth and assess the efficacy of the combination of MET inhibitors with IFNs in colorectal cancer.

Results: In colorectal cancer tissues, BATF2 was found to be significantly downregulated, and its expression negatively correlated with MET expression. Decreased BATF2 expression was associated with progression and shorter patient survival in colorectal cancer. BATF2 overexpression promoted apoptosis and inhibited proliferation, migration, and invasion in colorectal cancer cells, as well as dramatically blunted tumor xenograft growth. In addition, MET inhibitors in combination with IFNβ produced synergistic cytotoxicity both in vitro and in vivo.

Conclusions: Together, these novel findings suggest that BATF2, a tumor suppressor gene, is a potent negative regulator of HGF/MET signaling in colorectal cancer and may serve as a prognostic tumor marker. Furthermore, these results provide a rationale for combining MET inhibitors with IFNs in preclinical trials. Clin Cancer Res; 21(7); 1752–63. ©2015 AACR.
Depression and Quality of Life in Relation to Decreased Glomerular Filtration Rate Among Adults with Hypertension in Rural Northeast China
Authors: Guo Xiaofan , Li Zhao , Yu Shasha , Yang Hongmei , Guo Liang , Zheng Liqiang , Zhu Luoning , Zhang Yonghong , Sun Yingxian
Published: March 2015

Background/Aims: We aim to investigate the extent to which depression and quality of life might be associated with decreased glomerular filtration rate (GFR) in a large hypertensive population in rural Northeast China. Methods: A total of 5566 hypertensive participants aged 35 years and older were screened with a stratified cluster multistage sampling scheme in rural areas of Liaoning Province during 2012-2013. Decreased GFR was defined as estimated GFR <60 ml/min/1.73 m2. Results: The overall prevalence of decreased GFR was 3.2%. In the multivariable regression model, participants with moderate or greater depression had a greater risk for having a decreased GFR (OR: 1.739, 95%CI: 1.004 to 3.014) after full adjustment. Every 1-point increase of all the domains in WHOQOL-BREF, except for physical and environment domains, was significantly related to a lower risk for decreased GFR adjusting for age, gender and race. However, after fully adjustment, only social relations remained significant (OR: 0.899, 95%CI: 0.820 to 0.985). Increasing in total scores of WHOQOL-BREF was a protective factor against decreased GFR after fully adjustment. Conclusion: We found that moderate or greater depression and lower quality of life were associated with higher risks for developing decreased GFR.
Induction of Apoptosis by Hypertension Via Endoplasmic Reticulum Stress
Authors: Sun Yingying , Zhang Tong , Li Li , Wang Ji
Published: March 2015

Background/Aims: Endoplasmic reticulum (ER) stress is one of the intrinsic apoptosis pathways, and cardiac apoptosis can occur in cardiovascular diseases, such as hypertension. However, the mechanisms by which ER stress leads to apoptosis remain enigmatic, particularly in the progression from cardiac hypertrophy to diastolic heart failure due to hypertension. Methods: We used spontaneously hypertensive rats (SHRs) to investigate possible signalling pathways for ER stress. Results: We found that cardiac protein and mRNA levels of glucose-regulated protein 78 were up-regulated. In addition, the CHOP- and caspase-12-dependent pathways, but not that of JNK, were activated in the SHR rats. Conclusions: These results suggest that ER stress can contribute to myocardial apoptosis during hypertensive disease.
Drug Resistant Hypertension - No SIMPLE Way Out
Authors: Skrzypecki Janusz , Ufnal Marcin
Published: March 2015

Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3), the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal denervation. In order to identify causes of inconsistent results in renal denervation studies we look at basic science support for renal denervation and at designs of clinical trials.
The Neonatal Brain Is Not Protected by Osteopontin Peptide Treatment after Hypoxia-Ischemia
Authors: Bonestroo Hilde J.C. , Nijboer Cora H. , van Velthoven Cindy T.J. , van Bel Frank , Heijnen Cobi J.
Published: March 2015

Neonatal encephalopathy due to perinatal hypoxia-ischemia (HI) is a severe condition, and current treatment options are limited. Expression of endogenous osteopontin (OPN), a multifunction glycoprotein, is strongly upregulated in the brain after neonatal HI. Intracerebrally administered OPN has been shown to be neuroprotective following experimental neonatal HI and adult stroke. In the present study, we determined whether intranasal, intraperitoneal or intracerebral treatment with a smaller TAT-OPN peptide is neuroprotective in neonatal mice with HI brain damage. The TAT-OPN peptide exerts bioactivity as it was as potent as full-length OPN in inducing cell adhesion in an in vitro adhesion assay. Intranasal administration of TAT-OPN peptide immediately after HI (T0) or in a repetitive treatment schedule of T0, 3 h, day (D) 1, 2 and 3 after HI did not protect cerebral gray or white matter after HI. Intraperitoneal TAT-OPN treatment at T0 or in two extended treatment schedules (D5, 7, 9, 11, 13, 15 after HI or T0, D1, 3, 5, 7, 9, 11, 13 and 15 after HI) did not result in neuroprotection either. Moreover, no functional improvement (cylinder rearing test and adhesive removal task) was observed following TAT-OPN treatment in any of the intraperitoneal treatment schedules. We validated that the TAT-OPN peptide reached the brain after intranasal or intraperitoneal administration by using an HIV-TAT staining. Finally, also intracerebral administration of the TAT-OPN peptide 1 h after HI did not reduce cerebral damage. Our data show that administration of the TAT-OPN peptide did not exert neuroprotective effects on neonatal HI-induced brain injury or sensorimotor behavioral deficits.
Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo
Authors: Chen Tingfang , Zheng Li Yang , Xiao Wenzhen , Gui Dingkun , Wang Xiaoxia , Wang Niansong
Published: March 2015

Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg-1· d-1 and QLT0267 at 10 mg· kg-1· w-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.
In vitro Susceptibility of Tigecycline against Multidrug-Resistant Gram-Negative Strains: Etest versus Agar Dilution
Authors: Özkök Sezen , Togan Turhan , Yesilkaya Ayşegül , Timurkaynak Funda , Azap Özlem Kurt , Arslan Hande
Published: March 2015

Background and Aim: Tigecycline is a semi-synthetic tetracycline with activity against most multidrug-resistant (MDR) bacteria. Methods: We studied in vitro activity of tigecycline by agar dilution (AD) and Etest methods to evaluate their correlation. The study included 206 isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and MDR Acinetobacter baumannii recovered from blood cultures of patients of Baskent University between 2008 and 2010. Results: ESBL-producing E. coli had MIC50/MIC90 values of 0.5/0.5 µg/ml by AD and 0.25/0.5 µg/ml by Etest. ESBL-producing K. pneumoniae had MIC50/MIC90 values of 1/2 µg/ml by AD and 0.75/2 µg/ml by Etest, whereas MDR A. baumannii had MIC50/MIC90 values of 4/4 µg/ml by AD and 2/4 µg/ml by Etest. The correlation between AD and Etest was weak for ESBL-producing E. coli and strong for ESBL-producing K. pneumoniae and MDR A. baumannii. Tigecycline MIC values for ESBL-producing E. coli were lower than the tigecycline concentration, while they were higher than the concentrations attainable by treatment doses for A. baumannii. Conclusion: Tigecycline is an appropriate agent in the treatment of E. coli bacteremia, but it is not for treating A. baumannii bacteremia. Tigecycline could be used for K. pneumoniae bacteremia treatment after determining its MIC value. Determining the MIC value by gold-standard methods is more appropriate due to the correlation between Etest and AD at high MIC values.
Sigma-1 and N-Methyl-D-Aspartate Receptors: A Partnership with Beneficial Outcomes
Authors: Pabba Mohan , Sibille Etienne
Published: March 2015

Sigma-1 receptors (σ-1R) are interorganelle signaling molecules, which have been implicated in synaptic plasticity, primarily by enhancing the function of N-methyl-D-aspartate receptors (NMDARs). On the other hand, excessive influx of calcium via activated NMDAR can cause excitotoxicity. Yet, despite their NMDAR-enhancing role, multiple lines of evidence suggest that σ-1Rs are involved in neuroprotection. The mechanism underlying these intriguing opposing effects is not known. Recent studies now suggest the possibility that σ-1Rs could exert neuroprotective effects via targeted disruption of protein-protein interactions between NMDARs and their associated intracellular signaling machinery, specifically the neuronal nitric oxide synthase (nNOS). This targeted disruption of protein-protein interactions between NMDARs and nNOS results in lower levels of nitric oxide generation, thus having a neuroprotective effect. Here, we briefly summarize aspects of σ-1R-mediated enhancement of NMDAR function and possible neuroprotection. In-depth mechanistic understanding of σ-1R modulation of NMDAR function, which preserves Ca2+ homoeostasis while limiting excitotoxicity would provide valuable information for designing novel as well as improving prevailing therapeutic strategies.
Stress Experienced by Obstetrics and Gynecology Residents during Planned Laparoscopy: A Prospective, Multicentric, Observational, Blinded, and Comparative Study
Authors: Ducarme Guillaume , Bricou Alexandre , Chanelles Olivier , Sifer Christophe , Poncelet Christophe
Published: March 2015

Aims: To describe heart rate (HR) variations in surgical residents during laparoscopy and to assess their intraoperative stress. Methods: We performed a prospective, multicentric, observational, blinded, and comparative analysis of the HR in 75 obstetrics and gynecology residents during planned laparoscopy for infertility in five teaching hospitals with assisted reproductive technology centers. The surgical residents had neither heart disease nor were under medical treatment or using tobacco or drugs. We describe HR variations at 9 preselected operative steps using real-time noninvasive measures of the HR during laparoscopy. Results: Residents performed 124 laparoscopies for unexplained infertility. Their HR increased significantly during the introduction of the Palmer needle, umbilical port and second port, and during abdominopelvic exploration and dye test compared to the baseline HR, the HR after hand washing, at the end of surgery and during skin suture (91.6 ± 1.9, 104.8 ± 2.3, 95.3 ± 2.2, 93.7 ± 2.5, 90.7 ± 1.7 vs. 83.2 ± 1.6, 88.6 ± 1.9, 87.4 ± 2.1, 88.2 ± 1.9 bpm, respectively, p < 0.02). Conclusion: Our results point to a potential stress for the surgeon assessed by HR variations during planned laparoscopy compared to the baseline HR before surgery. This ‘static' stress can be repeated on the same day.
Activated Platelets Induce Estrogen Receptor β Expression in Endometriotic Stromal Cells
Authors: Zhang Qi , Ding Ding , Liu Xishi , Guo Sun-Wei
Published: March 2015

Background/Aims: Endometriosis is viewed first and foremost as an estrogen-dependent disease, featuring not only excessive estrogen production but also aberrant expression of estrogen receptors (ERs), particularly ERβ, that mediate the estrogen action. ERβ is the predominant ER in mediating estrogen action in endometriosis, and estrogen plays a vital role in the development of endometriosis; thus, ERβ is viewed as a strong candidate for therapeutic targeting. Given our recent finding that platelets aggregate in endometriotic lesions, we sought to investigate whether activated platelets can upregulate ERβ. Methods: Using primary endometriotic stromal cells derived from patients with ovarian endometriomas and platelets harvested from healthy donors, we performed real-time RT-PCR analysis of mRNA abundance (n = 8) and Western blot analysis of protein expression (n = 8) of ERα and ERβ when co-cultured with phosphate-buffered saline, platelets, thrombin alone, and platelets plus thrombin for 48 h. Results: Treatment of endometriotic stromal cells with activated platelets resulted in the upregulation of ERβ gene and protein expression. Conclusion: In the presence of aggregated and thus activated platelets in endometriotic lesions, ERβ, but not ERα, is upregulated in endometriotic stromal cells. Our result suggests that the use of antiplatelet therapy may have potential in the treatment of endometriosis.
Vascular Endothelial Growth Factor-C Expression as a Biomarker of Poor Prognosis in Esophageal Squamous Cell Carcinoma: A Meta-Analysis
Authors: Tullavardhana Thawatchai , Akranurakkul Prinya , Ungkitphaiboon Withoon , Songtish Dolrudee
Published: March 2015

Background: Vascular endothelial growth factor C (VEGF-C) is involved in the development and progression of tumor angio-/lymphangiogenesis. The purpose of this study is to evaluate whether VEGF-C expression is an indicator of aggressiveness and poor prognosis of esophageal squamous cell carcinoma (ESCC). Method: A meta-analysis was conducted to investigate the association between VEGF-C expression with clinicopathological characteristics and survival of ESCC patients. The dataset was defined by searching PubMed, Embase, Google Scholar, and the Cochrane database for appropriate articles published until April 2014. Result: The final analysis was made from 9 studies, including 656 ESCC patients. Positive VEGF-C expression was defined by immunohistochemistry (IHC) or mRNA expression analysis. The results demonstrated that VEGF-C expression was significantly associated with advanced-stage disease (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.37-3.84, P = 0.002), deeper tumor invasion, lymph node metastasis, and lymphatic invasion. The 5-year survival of VEGF-C expression-negative patients was found to be better than that of VEGF-C expression-positive patients (OR = 0.35, 95% CI = 0.21-0.58, P < 0.0001). However, there was no significant association between the VEGF-C expression levels and either poorer tumor differentiation or vascular invasion. Conclusion: The results of the meta-analysis strongly indicate that VEGF-C expression could function as a marker for predicting the aggressiveness and prognosis of ESCC.
Clinical Value of Ambulatory Blood Pressure
Authors: Mancia Giuseppe , Verdecchia Paolo
Published: March 2015

This article reviews the clinical value of ambulatory blood pressure (BP) vis-à-vis the traditional BP measurements taken in the physician’s office or in the hospital. Mention is initially made that longitudinal studies conducted in the general population or in hypertensive cohorts have shown that ambulatory BP provides a more accurate prediction of outcome than office BP. Namely, that (1) the risk of cardiovascular events increases in a less steep fashion with office than with 24-hour mean BP, (2) the 24-hour BP-dependent prediction is maintained after adjustment for office BP values, and (3) among individuals with normal office BP, those with increased ambulatory BP (masked hypertension) have an increased prevalence of organ damage, a more frequent unfavorable metabolic profile and a higher risk of new onset sustained hypertension, diabetes mellitus, and cardiovascular events than those with normal ambulatory BP. It is further mentioned, however, that more recently similar observations have been made for individuals with high office but normal ambulatory BP (white coat hypertension) suggesting a complementary role of out-of-office and office BP values in the determination of patients’ prognosis. The evidence in favor of an independent prognostic value also of some within 24-hour BP phenomena (night BP reduction or absolute values, short-term BP variations, and morning BP surge) is then critically appraised for its elements of strength and weakness. Finally, whether the clinical advantages of ambulatory BP make this approach necessary for all patients with hypertension is discussed. The conclusion is that this is at present still premature because crucial evidence pro or against routine use of this approach in untreated and treated hypertensives is not yet available. It will be crucial for future studies to determine whether, compared with a treatment guided by office BP, a treatment tailored on ambulatory BP allows to improve prevention or regression of organ damage as well as protection from major cardiovascular complications to a degree that justifies the complexity and cost of the procedure.
Practice Structure Improves Unconscious Transitional Memories by Increasing Synchrony in a Premotor Network
Authors: Song Sunbin , Gotts Stephen J. , Dayan Eran , Cohen Leonardo G.
Published: March 2015

Sequence learning relies on formation of unconscious transitional and conscious ordinal memories. The influence of practice type on formation of these memories that compose skill and systems level neural substrates is not known. Here, we studied learning of transitional and ordinal memories in participants trained on motor sequences while scanned using fMRI. Practice structure was varied or grouped (mixing or grouping sequences during training, respectively). Memory was assessed 30 min and 1 week later. Varied practice improved transitional memory and enhanced coupling of the dorsal premotor cortex with thalamus, cerebellum, and lingual and cingulate regions and greater transitional memory correlated with this coupling. Thus, varied practice improves unconscious transitional memories in proportion to coupling within a cortico-subcortical network linked to premotor cortex. This result indicates that practice structure influences unconscious transitional memory formation and identifies underlying systems level mechanisms.
A review of the genus Carchesiopygus Schedl (Coleoptera: Curculionidae:
Platypodinae), with keys to species
Authors: BEAVER ROGER A. , SANGUANSUB SUNISA
Published: March 2015

The ten species included by Schedl (1972) in the Oriental platypodine genus Carchesiopygus Schedl are reviewed. The genus is rediagnosed and restricted to the following species: Carchesiopygus wollastoni (Chapuis) (type species), C. alternantes Schedl, C. assamensis (Beeson), C. impariporus (Beeson), C. multidentatus (Strohmeyer) and C. oculatus (Beeson), and distinguished from Crossotarsus Chapuis and related genera. The following species are transferred to Platypus Herbst: Carchesiopygus dentipennis Schedl, Carchesiopygus lobacanthus Schedl, Crossotarsus acanthurus Beeson, Crossotarsus psilacanthurus Beeson. Keys are provided to males and females of Carchesiopygus. The taxonomy, distribution and biology of the species are briefly reviewed, and some new records included.
The Origin and Limits of the Near Proportionality between Climate Warming and Cumulative CO2 Emissions
Authors: MacDougall Andrew H. , Friedlingstein Pierre
Published: March 2015

The transient climate response to cumulative CO2 emissions (TCRE) is a useful metric of climate warming that directly relates the cause of climate change (cumulative carbon emissions) to the most used index of climate change (global mean near-surface temperature change). In this paper, analytical reasoning is used to investigate why TCRE is near constant over a range of cumulative emissions up to 2000 Pg of carbon. In addition, a climate model of intermediate complexity, forced with a constant flux of CO2 emissions, is used to explore the effect of terrestrial carbon cycle feedback strength on TCRE. The analysis reveals that TCRE emerges from the diminishing radiative forcing from CO2 per unit mass being compensated for by the diminishing ability of the ocean to take up heat and carbon. The relationship is maintained as long as the ocean uptake of carbon, which is simulated to be a function of the CO2 emissions rate, dominates changes in the airborne fraction of carbon. Strong terrestrial carbon cycle feedbacks have a dependence on the rate of carbon emission and, when present, lead to TRCE becoming rate dependent. Despite these feedbacks, TCRE remains roughly constant over the range of the representative concentration pathways and therefore maintains its primary utility as a metric of climate change.
Improved Simulation of Peak Flows under Climate Change: Postprocessing or Composite Objective Calibration?
Authors: Zhang Xujie , Booij Martijn J. , Xu Yue-Ping
Published: March 2015

Climate change is expected to have large impacts on peak flows. However, there may be bias in the simulation of peak flows by hydrological models. This study aims to improve the simulation of peak flows under climate change in Lanjiang catchment, east China, by comparing two approaches: postprocessing of peak flows and composite objective calibration. Two hydrological models [Soil and Water Assessment Tool (SWAT) and modèle du Génie Rural à 4 paramètres Journalier (GR4J)] are employed to simulate the daily flows, and the peaks-over-threshold method is used to extract peak flows from the simulated daily flows. Three postprocessing methods, namely, the quantile mapping method and two generalized linear models, are set up to correct the biases in the simulated raw peak flows. A composite objective calibration of the GR4J model by taking the peak flows into account in the calibration process is also carried out. The regional climate model Providing Regional Climates for Impacts Studies (PRECIS) with boundary forcing from two GCMs (HadCM3 and ECHAM5) under greenhouse gas emission scenario A1B is applied to produce the climate data for the baseline period and the future period 2011–40. The results show that the postprocessing methods, particularly quantile mapping method, can correct the biases in the raw peak flows effectively. The composite objective calibration also resulted in a good simulation performance of peak flows. The final estimated peak flows in the future period show an obvious increase compared with those in the baseline period, indicating there will probably be more frequent floods in Lanjiang catchment in the future.
Concealable Stigma and Occupational Segregation
Authors: Tilcsik András , Anteby Michel , Knight Carly R.
Published: March 2015

Numerous scholars have noted the disproportionately high number of gay and lesbian workers in certain occupations, but systematic explanations for this type of occupational segregation remain elusive. Drawing on the literatures on concealable stigma and stigma management, we develop a theoretical framework predicting that gay men and lesbians will concentrate in occupations that provide a high degree of task independence or require a high level of social perceptiveness, or both. Using several distinct measures of sexual orientation, and controlling for potential confounds, such as education, urban location, and regional and demographic differences, we find support for these predictions across two nationally representative surveys in the United States for the period 2008–2010. Gay men are more likely to be in female-majority occupations than are heterosexual men, and lesbians are more represented in male-majority occupations than are heterosexual women, but even after accounting for this tendency, common to both gay men and lesbians is a propensity to concentrate in occupations that provide task independence or require social perceptiveness, or both. This study offers a theory of occupational segregation on the basis of minority sexual orientation and holds implications for the literatures on stigma, occupations, and labor markets.
Labyrinthitis Ossificans
Authors: Bloch Sune Land , McKenna Michael John , Adams Joe , Friis Morten
Published: March 2015

Introduction:

It has been suggested that remodeling of the otic capsule is highly suppressed by the action of anti-resorptive signals emanating from structures of the inner ear space. Labyrinthitis ossificans (LO) is a severe complication to bacterial meningitis and is characterized by destruction of inner ear structures by the formation of new bone. The aim of this study was to explore the impact of LO on bone remodeling of the otic capsule.

Material and Methods:

In 11 human temporal bones with extensive LO and 10 control specimens, the degree of bone remodeling was explored indirectly by estimating the viability of osteocytes in perilabyrinthine bone and the mastoid.

Results:

The viability of osteocytes was significantly lower in the perilabyrinthine bone compared to the mastoid in both groups. However, the loss of perilabyrinthine osteocytes was the same in the 2 groups, and the presence of cartilage remnants appeared to be the same.

Conclusion:

This study indicates that the factors affecting bone remodeling of the otic capsule and the degeneration of osteocytes are not altered by wholesale destruction of inner ear soft tissue and its replacement by bone. Therefore, alternative mechanisms may be implicated in the suppression of capsular bone remodeling.