bluuebunny/crossref_metadata_2025 huggingface dataset:
Spin-Orbit Physics Giving Rise to Novel Phases in Correlated Systems: Iridates and Related Materials
Authors: Rau Jeffrey G. , Lee Eric Kin-Ho , Kee Hae-Young
Published: December 2015

Recently, the effects of spin-orbit coupling (SOC) in correlated materials have become one of the most actively studied subjects in condensed matter physics, as correlations and SOC together can lead to the discovery of new phases. Examples include unconventional magnetism, spin liquids, and strongly correlated topological phases such as topological superconductivity. Among candidate materials, iridium oxides (iridates) have been an excellent playground to uncover such novel phenomena. In this review, we discuss recent progress in iridates and related materials, focusing on the basic concepts, relevant microscopic Hamiltonians, and unusual properties of iridates in perovskite- and honeycomb-based structures. Perspectives on SOC and correlation physics beyond iridates are also discussed.
Central cholinergic synaptic vesicle loading obeys the set-point model in Drosophila
Authors: Cash Francesca , Vernon Samuel W. , Phelan Pauline , Goodchild Jim , Baines Richard A.
Published: December 2015

Experimental evidence shows that neurotransmitter release, from presynaptic terminals, can be regulated by altering transmitter load per synaptic vesicle (SV) and/or through change in the probability of vesicle release. The vesicular acetylcholine transporter (VAChT) loads acetylcholine into SVs at cholinergic synapses. We investigated how the VAChT affects SV content and release frequency at central synapses in Drosophila melanogaster by using an insecticidal compound, 5Cl-CASPP, to block VAChT and by transgenic overexpression of VAChT in cholinergic interneurons. Decreasing VAChT activity produces a decrease in spontaneous SV release with no change to quantal size and no decrease in the number of vesicles at the active zone. This suggests that many vesicles are lacking in neurotransmitter. Overexpression of VAChT leads to increased frequency of SV release, but again with no change in quantal size or vesicle number. This indicates that loading of central cholinergic SVs obeys the “set-point” model, rather than the “steady-state” model that better describes loading at the vertebrate neuromuscular junction. However, we show that expression of a VAChT polymorphism lacking one glutamine residue in a COOH-terminal polyQ domain leads to increased spontaneous SV release and increased quantal size. This effect spotlights the poly-glutamine domain as potentially being important for sensing the level of neurotransmitter in cholinergic SVs.
Spectral Investigation andIn VitroAntibacterial Evaluation of NiIIand CuIIComplexes of Schiff Base Derived from Amoxicillin andα-Formylthiophene (αft)
Authors: Chaudhary Narendra Kumar , Mishra Parashuram
Published: December 2015

Two new metal complexes of general formula M(Haαft)2[M =NiIIandCuII] of asymmetrical Schiff base ligand (HL = Haαft) derived from amoxicillin andα-formylthiophene have been prepared and characterized by various physicochemical and spectral techniques. Molar conductance measurement indicates nonelectrolytic nature of the metal complexes. FT-IR spectral study reveals the ligation of metal ions at two different nitrogen [NN] donor sites of Haαft. FT-IR and electronic absorption spectral evidences suggest distorted tetrahedral and square planar geometry forCuIIandNiIIcomplexes, respectively. The structure optimization by molecular mechanics (MM) force field calculation through ArgusLab 4.0.1 version software also supports the concerned geometry of the complexes. The cell dimensions as suggested by XRPD study,a(6.753 Å),b(13.904 Å),c(20.122 Å),α(142.76°),β(106.580°), andγ(72.4343°) forCuIIanda(24.2547 Å),b(6.6371 Å),c(5.5047 Å) (α=β=γ= 90°) forNiIIcomplexes, are in good agreement with their triclinic and orthorhombic crystal systems. Particle size calculation by Scherrer’s formula indicates nanocrystalline nature of the complexes. The antibacterial sensitivity study suggests promising activities of Haαft (Ligand) and M(Haαft)2complexes against four clinical pathogenic bacteria, namely,E. coli,P. vulgaris,P. aeruginosa, andS. aureus, though being less active than the standard drug amikacin.
Biological Restoration of a Fractured Anterior Tooth with the Use of Dentine Pin (Biopins)
Authors: Nogueira Lilian Capanema , Tavano Karine Taís Aguiar , Ferraz Nayara Kelly Lyrio , Glória José Cristiano Ramos , Botelho Adriana Maria
Published: December 2015

This case study describes the esthetic and functional reconstruction of a fractured maxillary central incisor. Due to the requirement for additional retention, treatment was performed using the homogenous technique of biological restoration associated with cementation of posts made from human dentin (biopins). This type of treatment is a new alternative to conventional techniques and favors the dental esthetic and function, as well as biocompatibility, and is an inexpensive procedure.
Evaluation of the Acceleration and Deceleration Phase-Rectified Slope to Detect and Improve IUGR Clinical Management
Authors: Tagliaferri Salvatore , Fanelli Andrea , Esposito Giuseppina , Esposito Francesca Giovanna , Magenes Giovanni , Signorini Maria Gabriella , Campanile Marta , Martinelli Pasquale
Published: December 2015

Objective.This study used a new method called Acceleration (or Deceleration) Phase-Rectified Slope, APRS (or DPRS) to analyze computerized Cardiotocographic (cCTG) traces in intrauterine growth restriction (IUGR), in order to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate, and to enhance the prediction of neonatal outcome.Method.Cardiotocograms from a population of 59 healthy and 61 IUGR fetuses from the 30th gestation week matched for gestational age were included. APRS and DPRS analysis was compared to the standard linear and nonlinear cCTG parameters. Statistical analysis was performed through thet-test, ANOVA test, Pearson correlation test and receiver operator characteristic (ROC) curves (p<0,05).Results.APRS and DPRS showed high performance to discriminate between Healthy and IUGR fetuses, according to gestational week. A linear correlation with the fetal pH at birth was found in IUGR. The area under the ROC curve was 0.865 for APRS and 0.900 for DPRS before the 34th gestation week.Conclusions.APRS and DPRS could be useful in the identification and management of IUGR fetuses and in the prediction of the neonatal outcome, especially before the 34th week of gestation.
Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients
Authors: Rodriguez-Auad Juan Pablo , Rojas-Montes Othon , Maldonado-Rodriguez Angelica , Alvarez-Muñoz Ma. Teresa , Muñoz Onofre , Torres-Ibarra Rocio , Vazquez-Rosales Guillermo , Lira Rosalia
Published: December 2015

Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10copies/mL in liquid plasma and 4.1 log10copies/mL in DPS, with a correlation coefficient ofR= 0.83. A 1.1 kb fragment of HIVpolcould be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1polsequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.
Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis
Authors: Bovenzi Cory D. , Hamilton James , Tassone Patrick , Johnson Jennifer , Cognetti David M. , Luginbuhl Adam , Keane William M. , Zhan Tingting , Tuluc Madalina , Bar-Ad Voichita , Martinez-Outschoorn Ubaldo , Curry Joseph M.
Published: December 2015

Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147.Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses.Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p<0.001for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p<0.0001for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival.Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.
Flower-Like Mn-Doped CeO2Microstructures: Synthesis, Characterizations, and Catalytic Properties
Authors: Liu Ling , Shi Jingjing , Zhang Xiaojun , Liu Jianzhou
Published: December 2015

Mn-doped CeO2flower-like microstructures have been synthesized by a facile method, involving the precipitation of metallic alkoxide precursor in a polyol process from the reaction of CeCl3·7H2O with ethylene glycol in the presence of urea followed by calcination. By introducing manganese ions, the composition can be freely manipulated. To investigate whether there was a hybrid synergic effect in CH4combustion reaction, further detailed characteristics of Mn-doped CeO2with various manganese contents were revealed by XRD, Raman, FT-IR, SEM, EDS, XPS, OSC, H2-TPR, and N2adsorption-desorption measurements. The doping manganese is demonstrated to increase the storage of oxygen vacancy for CH4and enhance the redox capability, which can efficiently convert CH4to CO2and H2O under oxygen-rich condition. The excellent catalytic performance of MCO-3 sample, which was obtained with the starting Mn/Ce ratios of 0.2 in the initial reactant compositions, is associated with the larger surface area and richer surface active oxygen species.
Fetal Midgut Volvulus with a Cystic Appearance, Accompanying a Sinus Rhythm and an Increased Peak Systolic Velocity without Anemia
Authors: Kaba Metin , Oksuzoglu Aysegul , Kaba Gokcen , Timur Hakan , Akbaba Eren , Turgut Kadriye
Published: December 2015

A midgut volvulus rarely occurs in a fetus; however, when it does, it requires an immediate diagnosis and surgery. Thirty-week pregnant was referred to our clinic with a diagnosis of a fetal abdominal cystic mass and preterm labor. The initial ultrasound examination revealed a female fetus with a 55 × 50 mm cystic mass in the lower abdomen, which was preliminarily diagnosed as an ovarian cyst. There was a sinusoidal rhythm on cardiography. The middle cerebral artery peak systolic velocity was 60.4 cm/sec, compatible with 1.49 MoMs that suggested fetal anemia on Doppler examination. Uterine contractions were observed with tocography and maternal hydration was administered for tocolytic treatment. Despite hydration, uterine contractions continued and the infant was delivered. A newborn ultrasonographic evaluation revealed a 6 cm abdominal cyst, and plain abdominal radiographs revealed distended loops of the small bowel on the left side. Emergency surgery was performed. A midgut volvulus leading to dilatation and necrosis of the small bowel without anatomical causes was observed during laparotomy. The necrotic bowel loop was resected and an end-to-end anastomosis was performed. The newborn died due to multiorgan failure. Obstetricians should be familiar with the appropriate diagnosis and management of a fetal volvulus.
A Novel Geometric Modification to the Newton-Secant Method to Achieve Convergence of Order1+2and Its Dynamics
Authors: Fernández-Torres Gustavo
Published: December 2015

A geometric modification to the Newton-Secant method to obtain the root of a nonlinear equation is described and analyzed. With the same number of evaluations, the modified method converges faster than Newton’s method and the convergence order of the new method is1+2≈2.4142. The numerical examples and the dynamical analysis show that the new method is robust and converges to the root in many cases where Newton’s method and other recently published methods fail.
Evidence-Based Decision Making in Public Health: Capacity Building for Public Health Students at King Saud University in Riyadh
Authors: Wahabi Hayfaa A. , Siddiqui Amna Rehana , Mohamed Ashry G. , Al-hazmi Ali M. , Zakaria Nasriah , Al-Ansary Lubna A.
Published: December 2015

Translation of research evidence into public health programs is lagging in Eastern Mediterranean Region. Graduate level public health curriculum at King Saud University (KSU), College of Medicine, Riyadh, is designed to equip students to integrate best available evidence in public health decision making. The objectives of study were to explore students’ opinion about the evidence based public health (EBPH) courses and to survey the knowledge, opinion, and attitude of the students towards EBPH and perceived barriers for implementation of EBPH in decision making in public health. EBPH courses are designed based on a sequential framework. A survey was conducted at the completion of EBPH courses. Forty-five graduate students were invited to complete a validated self-administered questionnaire. It included questions about demography, opinion, and attitude towards EBPH and perceived barriers towards implementation of EBPH in the work environment. The response rate was 73%. Mean age of students was 30.1 (SD 2.3) years, and 51% were males. More than 80% had sound knowledge and could appreciate the importance of EBPH. The main perceived barriers to incorporate EBPH in decision making were lack of system of communication between researchers and policy makers and scarcity of research publications related to the public health problems.
Woody Species Diversity in Traditional Agroforestry Practices of Dellomenna District, Southeastern Ethiopia: Implication for Maintaining Native Woody Species
Authors: Molla Abiot , Kewessa Gonfa
Published: December 2015

The major impact of humans on forest ecosystems including loss of forest area, habitat fragmentation, and soil degradation leads to losses of biodiversity. These problems can be addressed by integration of agriculture with forests and maintaining the existing forests. This study was initiated to assess woody species diversity of traditional agroforestry practices. Three study sites (Burkitu, Chire, and Erba) were selected based on the presence of agroforestry practice. Forty-eight (48) sample quadrants having an area of 20 m × 20 m, 16 sample quadrants in each study site, were systematically laid using four transect lines at different distance. The diversity of woody species was analyzed by using different diversity indices. A total of 55 woody species belonging to 31 families were identified and documented. There were significantly different (P<0.05) among the study Kebeles (peasant associations). Mangifera indica, Entada abyssinica, and Croton macrostachyus were found to have the highest Important Value Index. The results confirmed that traditional agroforestry plays a major role in the conservation of native woody species. However, threats to woody species were observed. Therefore, there is a need to undertake conservation practices before the loss of species.
The Context Matters: Outcome Probability and Expectation Mismatch Modulate the Feedback Negativity When Self-Evaluation of Response Correctness Is Possible
Authors: Leue Anja , Cano Rodilla Carmen , Beauducel André
Published: December 2015

Individuals typically evaluate whether their performance and the obtained feedback match. Previous research has shown that feedback negativity (FN) depends on outcome probability and feedback valence. It is, however, less clear to what extent previous effects of outcome probability on FN depend on self-evaluations of response correctness. Therefore, we investigated the effects of outcome probability on FN amplitude in a simple go/no-go task that allowed for the self-evaluation of response correctness. We also investigated effects of performance incompatibility and feedback valence. In a sample ofN=22participants, outcome probability was manipulated by means of precues, feedback valence by means of monetary feedback, and performance incompatibility by means of feedback that induced a match versus mismatch with individuals’ performance. We found that the 100% outcome probability condition induced a more negative FN following no-loss than the 50% outcome probability condition. The FN following loss was more negative in the 50% compared to the 100% outcome probability condition. Performance-incompatible loss resulted in a more negative FN than performance-compatible loss. Our results indicate that the self-evaluation of the correctness of responses should be taken into account when the effects of outcome probability and expectation mismatch on FN are investigated.
Exploring the Unmet Needs of the Patients in the Outpatient Respiratory Medical Clinic: Patients versus Clinicians Perspectives
Authors: Jensen Lone Birgitte Skov , Brinkjær Ulf , Larsen Kristian , Konradsen Hanne
Published: December 2015

Aim. Developing a theoretical framework explaining patients’ behaviour and actions related to unmet needs during interactions with health care professionals in hospital-based outpatient respiratory medical clinics.Background. The outpatient respiratory medical clinic plays a prominent role in many patients’ lives regarding treatment and counselling increasing the need for a better understanding of patients’ perspective to the counselling of the health care professionals.Design. The study is exploratory and based on Charmaz’s interpretation of grounded theory.Methods. The study included 65 field observations with a sample of 43 patients, 11 doctors, and 11 nurses, as well as 30 interviews with patients, conducted through theoretical sampling from three outpatient respiratory medical clinics in Denmark.Findings. The patients’ efforts to share their significant stories triggered predominantly an adaptation or resistance behaviour, conceptualized as “fitting in” and “fighting back” behaviour, explaining the patients’ counterreactions to unrecognized needs during the medical encounter.Conclusion. Firstly this study allows for a better understanding of patients’ counterreactions in the time-pressured and, simultaneously, tight structured guidance program in the outpatient clinic. Secondly the study offers practical and ethical implications as to how health care professionals’ attitudes towards patients can increase their ability to support emotional suffering and increase patient participation and responsiveness to guidance in the lifestyle changes.
Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation‐Induced Tactile Hypersensitivity in the Rat
Authors: Jang Jun Ho , Nam Taick Sang , Jun Jaebeom , Jung Se Jung , Kim Dong-Wook , Leem Joong Woo
Published: December 2015

We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation‐induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind‐paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group‐I metabotropic Glu receptor (mGluR) antagonists and group‐II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES‐induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES‐induced hypersensitivity. When the same injections were administered after establishment of ES‐induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA‐ and PKC‐dependent mechanisms mediated mainly by NMDAR activation are involved in Glu‐induced nociceptor sensitization and subsequent hypersensitivity.
A Case Report on the Successful Treatment ofStreptococcus pneumoniae-Induced Infectious Abdominal Aortic Aneurysm Initially Presenting with Meningitis
Authors: Kawatani Yohei , Nakamura Yoshitsugu , Hayashi Yujiro , Taneichi Tetsuyoshi , Ito Yujiro , Kurobe Hirotsugu , Suda Yuji , Hori Takaki
Published: December 2015

Infectious abdominal aortic aneurysms often present with abdominal and lower back pain, but prolonged fever may be the only symptom. Infectious abdominal aortic aneurysms initially presenting with meningitis are extremely rare; there are no reports of their successful treatment. Cases withStreptococcus pneumoniaeas the causative bacteria are even rarer with a higher mortality rate than those caused by other bacteria. We present the case of a 65-year-old man with lower limb weakness and back pain. Examination revealed fever and neck stiffness. Cerebrospinal fluid showed leukocytosis and low glucose levels. The patient was diagnosed with meningitis and bacteremia caused byStreptococcus pneumoniaeand treated with antibiotics. Fever, inflammatory response, and neurologic findings showed improvement. However, abdominal computed tomography revealed an aneurysm not present on admission. Antibiotics were continued, and a rifampicin soaked artificial vascular graft was implanted. Tissue cultures showed no bacteria, and histological findings indicated inflammation with high leukocyte levels. There were no postoperative complications or neurologic abnormalities. Physical examination, blood tests, and computed tomography confirmed there was no relapse over the following 13 months. This is the first reported case of survival of a patient with an infectious abdominal aortic aneurysm initially presenting with meningitis caused byStreptococcus pneumoniae.
Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer
Authors: Li Weimin , Fan Mengdi , Chen Yina , Zhao Qian , Song Caiyun , Yan Ye , Jin Yin , Huang Zhiming , Lin Chunjing , Wu Jiansheng
Published: December 2015

Background/Aims: Melatonin, synthesized by the pineal gland and released into the blood, appears to have antitumour properties; however, the mechanisms of its anti-cancer effects are largely unknown, especially in stomach cancer. Here, we explore the antitumour activity of melatonin in a gastric cancer cell line (AGS) and analyse its molecular mechanisms. Methods: AGS cells were treated with melatonin, and cell viability was assessed using a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis, and protein expression was examined by Western blotting. Results: Melatonin significantly inhibited cell viability, clone formation, and cell migration and invasion and induced apoptosis in AGS cells. Moreover, MAPK pathways (p38, JNK and ERK) were activated by melatonin treatment, which also significantly increased caspase-3 cleavage and Bax protein expression and decreased Bcl-2 protein expression in a time-dependent manner. Our results demonstrate that p38 and JNK inhibitors (SB203580 and SP600125, respectively) prevented melatonin-induced apoptosis; thus, the propensity of p38 MAPK and JNK to promote apoptosis could be at least partly due to the inhibition of NF-κB p65 activation by p38 and JNK. Finally, melatonin was able to strengthen cisplatin-mediated antitumour effects in human gastric carcinoma cells by up-regulating the expression of Bax, down-regulating the expression of Bcl-2 and activating the caspase-dependent apoptotic pathway. Conclusion: Melatonin induced apoptosis in AGS cells by activating the caspase-dependent apoptotic pathway and by inhibiting the nuclear translocation of NF-κB p65, two processes that are regulated by p38 and JNK. Furthermore, melatonin significantly enhanced the anti-tumour effects of cisplatin, with low systemic toxicity. These new findings suggest that melatonin may act as a potent anti-tumour agent and may have great potential as an adjuvant therapy in the future.
Mitochondrial Proteomics Approach Reveals Voltage-Dependent Anion Channel 1 (VDAC1) as a Potential Biomarker of Gastric Cancer
Authors: Gao Wen , Xu Jing , Wang Fuqiang , Zhang Long , Peng Rui , Zhu Yunxia , Tang Qiyun , Wu Jindao
Published: December 2015

Background/Aims: Gastric cancer (GC) remains the second leading cause of cancer-related deaths in the world. Successful early cancer detection is hampered by lack of highly sensitive and specific biomarkers. Mitochondrial dysfunction contributes to an aggressive carcinogenic phenotype of many cancers. We hypothesized that changes in the mitochondrial proteome are required to support development of GC. Methods: TMT method followed by mass spectrometry analysis was utilized to quantify alterations in protein abundance in mitochondria enriched between noncancer and gastric cancer tissues. Results: Of a total data set that included 738 identified proteins, about 40.1% were found to be mitochondrial and associated proteins. Among them, 234 proteins were at least 1.5-fold up- or down-regulated in the gastric cancer compared with the adherent normal tissues. A number of markers (e.g. HSP70, HSP60, HSP90, leucine-rich pentatricopeptide repeat containing (LRPPRC), SOD2 and cathepsin B) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in mitochondrial oxidative phosphorylation and active fatty acid oxidation were firstly identified differentially expressed in GC samples. Our findings also suggest that VDAC1 may be a novel biomarker for GC. Conclusion: The results show that subcellular proteomics of tumor tissue is feasible and a promising avenue for exploring oncogenesis.
Oxaliplatin Induced Suicidal Death of Human Erythrocytes
Authors: Fazio Antonella , Briglia Marilena , Faggio Caterina , Alzoubi Kousi , Lang Florian
Published: December 2015

Background/Aims: The alkylating drug oxaliplatin is widely used for chemotherapy of malignancy. Oxaliplatin is effective by inducing both, necrosis and apoptosis. Similar to necrosis or apoptosis of nucleated cells, erythrocytes may enter hemolysis, which is apparent from hemoglobin release or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress and/or Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether and how oxaliplatin induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was quantified utilizing annexin-V-binding, cell volume estimated from forward scatter, hemolysis deduced from hemoglobin release, [Ca2+]i determined utilizing Fluo-3 fluorescence, and reactive oxygen species (ROS) abundance visualized using 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. Results: A 48 hours exposure of human erythrocytes to oxaliplatin (10 µg/ml) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter, significantly increased Fluo-3 fluorescence, and significantly increased DCFDA fluorescence. The effect of oxaliplatin on annexin-V-binding and forward scatter was rather augmented by removal of extracellular Ca2+, but was significantly blunted in the presence of the antioxidant N-acetyl-cysteine (1 mM). Conclusions: Oxaliplatin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect partially dependent on ROS formation.
Isocitrate Dehydrogenase 2 Suppresses the Invasion of Hepatocellular Carcinoma Cells via Matrix Metalloproteinase 9
Authors: Tian Guo-Yan , Zang Shu-Fei , Wang Lei , Luo Yan , Shi Jun-Ping , Lou Guo-Qiang
Published: December 2015

Background/Aims: Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial NADP-dependent isocitrate dehydrogenase, and has been found to be a tumor suppressor in several types of tumors. However, the roles of IDH2 in hepatocellular carcinoma (HCC) as well as underlying mechanisms remain unknown. Methods: The IDH2 and matrix metalloproteinase 9 (MMP9) levels in the specimens from 24 HCC patients were investigated by Western blot and ELISA, respectively. Their relationship was examined by correlation analyses. Patient survival with high IDH2 levels and low IDH2 levels was compared. IDH2 levels and MMP9 levels were modified in a human HCC cell line. The effects of IDH2 or MMP9 modulation on the expression of the other were analyzed. The effects of IDH2 on cell invasion were analyzed in a transwell cell invasion assay. The dependence of nuclear factor κB (NF-κB) signaling was examined using a specific inhibitor. Results: The IDH2 levels significantly decreased in HCC, and were lower in HCC with metastases, compared to those without metastases. IDH2 levels inversely correlated with MMP9 levels in HCC. HCC patients with Low IDH2 had lower 5-year survival. MMP9 levels did not regulate IDH2 levels, while IDH2 inhibited MMP9 levels in HCC cells, in a NF-κB signaling dependent manner, possibly through iκB, to suppress HCC cell invasion. Conclusions: Down regulation of IDH2 may promote HCC cell invasion via NF-κB-dependent increases in MMP9 activity. IDH2 may be a potential therapeutic target for HCC.
Mesenchymal Stem Cell-Derived Exosomes Improve the Microenvironment of Infarcted Myocardium Contributing to Angiogenesis and Anti-Inflammation
Authors: Teng Xiaomei , Chen Lei , Chen Weiqian , Yang Junjie , Yang Ziying , Shen Zhenya
Published: December 2015

Background/Aims: Bone marrow mesenchymal stem cells (MSCs) widely applied for treating myocardial infarction face survival challenges in the inflammatory and ischemia microenvironment of acute myocardial infarction. The study hypothesized that MSC-derived exosomes play a significant role in improving microenvironment after acute myocardial infarction and aimed to investigate the paracrine effects of exosomes on angiogenesis and anti-inflammatory activity. Methods: MSCs were cultured in DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin for 48 h. MSC-derived exosomes were isolated using ExoQuick-TC. Tube formation and T-cell proliferation assays were performed to assess the angiogenic potency of MSC-derived exosomes. Acute myocardial infarction was induced in Sprague-Dawley rats, and myocardium bordering the infarcted zone was injected at four different sites with phosphate-buffered saline (PBS, control), MSC-derived exosomes, and exosome-depleted MSC culture medium. Results: MSC-derived exosomes significantly enhanced the tube formation of human umbilical vein endothelial cells, impaired T-cell function by inhibiting cell proliferation in vitro, reduced infarct size, and preserved cardiac systolic and diastolic performance compared with PBS markedly enhancing the density of new functional capillary and hence blood flow recovery in rat myocardial infarction model. Conclusions: Exosomes stimulate neovascularization and restrain the inflammation response, thus improving heart function after ischemic injury.
Precision Medicine and Non-Colorectal Cancer Liver Metastases: Fiction or Reality?
Authors: Liakopoulou Effie , Knuth Alexander
Published: December 2015

Background: Non-colorectal liver metastases (nCRLM) constitute a variety of heterogeneous diseases and a considerable therapeutic challenge. Management is based on the primary tumor and the clinical course. In the era of precision medicine (PM) we know that cancer is heterogeneous within the tumor and across different sites. Methods: We give an overview of the path to PM through ‘omics' beyond genomics. We refer to the experience gained to date from models such as colorectal cancer and we discuss the opportunity offered by PM for the management of nCRLM. Results: In order to best characterize and track tumor biological behaviors as well as to understand mechanisms of response to therapy and survival we suggest the application of novel clinical trial designs, a dynamic approach with serial monitoring involving evaluation of primary and metastatic sites. Quality and standardization of tissue acquisition and biobanking is a precondition for the reliability of this approach. Conclusion: The application of PM is increasingly becoming a reality. Elucidating the mysteries of tumors in complex settings can only be achieved with the approach PM offers. nCRLM may serve as a model for the application of PM principles and techniques in understanding individual diseases and also cancer as an entity and therapeutic challenge.
Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain
Authors: Giatti Silvia , Foglio Benedetta , Romano Simone , Pesaresi Marzia , Panzica Giancarlo , Garcia-Segura Luis Miguel , Caruso Donatella , Melcangi Roberto Cosimo
Published: December 2015

The enzymatic conversion of progesterone and testosterone by the enzyme 5alpha-reductase exerts a crucial role in the control of nervous function. The effects of finasteride in the brain, an inhibitor of this enzyme used for the treatment of human benign prostatic hyperplasia and androgenic alopecia, have been poorly explored. Therefore, the effects of a subchronic treatment with finasteride at low doses (3 mg/kg/day) and the consequences of its withdrawal on neuroactive steroid levels in plasma, cerebrospinal fluid and some brain regions as well as on the expression of classical and non-classical steroid receptors have been evaluated in male rats. After subchronic treatment (i.e., for 20 days) the following effects were detected: (i) depending on the compartment considered, alteration in the levels of neuroactive steroids, not only in 5alpha-reduced metabolites but also in its precursors and in neuroactive steroids from other steroidogenic pathways and (ii) an upregulation of the androgen receptor in the cerebral cortex and beta3 subunit of the GABA-A receptor in the cerebellum. One month after the last treatment (i.e., withdrawal period), some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex, an increase of dihydroprogesterone in the cerebellum, a decrease of dihydrotestosterone in plasma). Moreover, other changes in neuroactive steroid levels, steroid receptors (i.e., an upregulation of the estrogen receptor alpha and a downregulation of the estrogen receptor beta in the cerebral cortex) and GABA-A receptor subunits (i.e., a decrease of alpha 4 and beta 3 mRNA levels in the cerebral cortex) were detected. These findings suggest that finasteride treatment may have broad consequences for brain function.
Políticas de Controle da Desordem Urbana: A Experiência das Unidades de Ordem Pública na Cidade do Rio de Janeiro
Authors: Carneiro Leandro Piquet , Bondarovsky Bruno
Published: December 2015

Este artigo descreve e analisa o processo de desenho e execução das Unidades de Ordem Pública (UOP) na Cidade do Rio de Janeiro. Trata-se de um programa desenvolvido por gestores locais da Secretaria Municipal da Ordem Pública com a participação de pesquisadores do Núcleo de Pesquisa de Políticas Públicas da Universidade de São Paulo entre 2010 e 2013. As oito Unidades de Ordem Pública instaladas permitiram testar em pequena escala novos modelos de operação, gestão e controle da ordem pública no município. São descritas as características, ações, custos e operações do programa, com a apresentação de dados e informações que indicam seus efeitos, assim como as possibilidades de manutenção, ampliação e disseminação.
Cenário de Práticas para a Formação Universitária: O Olhar dos Estudantes
Authors: Cervato-Mancuso Ana Maria , Nunes Nadine Marques , Andrade Elisabete Agrela de
Published: December 2015

A Educação Universitária tem como desafio atual o aprimoramento de suas práticas pedagógicas. O objetivo do presente trabalho foi conhecer os valores e significados atribuídos, por estudantes do curso de Nutrição da USP, às suas experiências de extensão universitária. Trata-se de um estudo de abordagem qualitativa, utilizando-se o grupo focal como técnica de coleta de dados. Foram realizados cinco grupos, divididos entre as principais atividades realizadas: Empresa Júnior, Iniciação Científica, Associação Atlética, Clínica de Nutrição e Jornada Universitária. Verifica-se que os estudantes consideraram que cada atividade colabora com o desenvolvimento de competência ou habilidade profissional específica. Dentre elas, destacam-se: autonomia, autoconfiança, comunicação interpessoal, comunicação social, trabalho em equipe, visão ampliada dos problemas e das necessidades sociais, conhecimento técnico e teórico específico, atenção integral, contato com a realidade profissional, entre outras. Conclui-se que as atividades de extensão universitária contribuem tanto para que, especificamente na área da saúde, os projetos pedagógicos sejam flexíveis para a incorporação dessas atividades.
Search for Rare Copy-Number Variants in Congenital Heart Defects Identifies Novel Candidate Genes and a Potential Role for FOXC1 in Patients With Coarctation of the Aorta
Authors: Sanchez-Castro Marta , Eldjouzi Hadja , Charpentier Eric , Busson Pierre-François , Hauet Quentin , Lindenbaum Pierre , Delasalle-Guyomarch Béatrice , Baudry Adrien , Pichon Olivier , Pascal Cécile , Lefort Bruno , Bajolle Fanny , Pezard Philippe , Schott Jean-Jacques , Dina Christian , Redon Richard , Gournay Véronique , Bonnet Damien , Le Caignec Cédric
Published: December 2015

Background—

Congenital heart defects are the most frequent malformations among newborns and a frequent cause of morbidity and mortality. Although genetic variation contributes to congenital heart defects, their precise molecular bases remain unknown in the majority of patients.

Methods and Results—

We analyzed, by high-resolution array comparative genomic hybridization, 316 children with sporadic, nonsyndromic congenital heart defects, including 76 coarctation of the aorta, 159 transposition of the great arteries, and 81 tetralogy of Fallot, as well as their unaffected parents. We identified by array comparative genomic hybridization, and validated by quantitative real-time polymerase chain reaction, 71 rare de novo (n=8) or inherited (n=63) copy-number variants (CNVs; 50 duplications and 21 deletions) in patients. We identified 113 candidate genes for congenital heart defects within these CNVs, including
BTRC
,
CHRNB3
,
CSRP2BP
,
ERBB2
,
ERMARD
,
GLIS3
,
PLN
,
PTPRJ
,
RLN3
, and
TCTE3
. No de novo CNVs were identified in patients with transposition of the great arteries in contrast to coarctation of the aorta and tetralogy of Fallot (
P
=0.002; Fisher exact test). A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. This significant enrichment (
P
<0.0001; permutation test) was not observed for the CNVs identified in patients with transposition of the great arteries and tetralogy of Fallot. We hypothesize that these CNVs may alter the expression of genes regulated by FOXC1. Foxc1 belongs to the forkhead transcription factors family, which plays a critical role in cardiovascular development in mice.

Conclusions—

These data suggest that deregulation of
FOXC1
or its downstream genes play a major role in the pathogenesis of coarctation of the aorta in humans.
Factors Affecting Bleeding and Stent Thrombosis in Clinical Trials Comparing Bivalirudin With Heparin During Percutaneous Coronary Intervention
Authors: Bittl John A. , He Yulei , Lang Christopher D. , Dangas George D.
Published: December 2015

Background—

Patients treated with bivalirudin in randomized clinical trials of percutaneous coronary intervention generally have less bleeding but more acute stent thrombosis (ST) than do patients treated with heparin, but differences have varied among trials.

Methods and Results—

We modeled the risk of major hemorrhage and ischemic outcomes 30 days after percutaneous coronary intervention by treatment assignment and the use of adjunctive therapies in 18 randomized clinical trials enrolling 41 871 patients. Overall bivalirudin caused less major bleeding (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.76), more ST (OR, 1.58; 95% CI, 1.19–2.09), and no difference in mortality (OR, 0.93; 95% CI, 0.77–1.14) than heparin. A risk–benefit analysis identified 19 fewer bleeds and 5 more STs for every 1000 patients treated with bivalirudin in place of heparin. No significant bleeding advantage of bivalirudin over heparin could be identified in randomized clinical trials when transradial access (OR, 0.89; 95% CI, 0.57–1.41) and planned glycoprotein IIb/IIIa inhibitors were used with bivalirudin in the majority of patients (OR, 1.07; 95% CI, 0.87–1.31). The use of prasugrel or ticagrelor eliminated bleeding differences (OR, 0.80; 95% CI, 0.63–1.03) but did not reduce the risk of ST after bivalirudin (OR, 2.20; 95% CI, 1.48–3.27).

Conclusions—

Substituting bivalirudin for heparin conferred a tradeoff between bleeding and ST. Transradial access, adjunctive glycoprotein IIb/IIIa inhibitors, and potent P2Y
12
inhibitors attenuated the bleeding advantage of bivalirudin over heparin but had no apparent effect on early ST. New approaches to reduce bleeding and ischemic complications during percutaneous coronary intervention warrant further investigation.
Risk of Adverse Cardiac and Bleeding Events Following Cardiac and Noncardiac Surgery in Patients With Coronary Stent
Authors: Saia Francesco , Belotti Laura Maria Beatrice , Guastaroba Paolo , Berardini Alessandra , Rossini Roberta , Musumeci Giuseppe , Tarantini Giuseppe , Campo Gianluca , Guiducci Vincenzo , Tarantino Fabio , Menozzi Alberto , Varani Elisabetta , Santarelli Andrea , Tondi Stefano , De Palma Rossana , Rapezzi Claudio , Marzocchi Antonio
Published: December 2015

Background—

Epidemiology and consequences of surgery in patients with coronary stents are not clearly defined, as well as the impact of different stent types in relationship with timing of surgery.

Methods and Results—

Among 39 362 patients with previous coronary stenting enrolled in a multicenter prospective registry and followed for 5 years, 13 128 patients underwent 17 226 surgical procedures. The cumulative incidence of surgery at 30 days, 6 months, 1 year, and 5 years was 3.6%, 9.4%, 14.3%, and 40.0%, respectively, and of cardiac and noncardiac surgery was 0.8%, 2.1%, 2.6%, and 4.0% and 1.3%, 5.1%, 9.1%, and 31.7%, respectively. We assessed the incidence and the predictors of cardiac death, myocardial infarction, and serious bleeding event within 30 days from surgery. Cardiac death occurred in 438 patients (2.5%), myocardial infarction in 256 (1.5%), and serious bleeding event in 1099 (6.4%). Surgery increased 1.58× the risk of cardiac death during follow-up. Along with other risk factors, the interplay between stent type and time from percutaneous coronary intervention to surgery was independently associated with cardiac death/myocardial infarction. In comparison with bare-metal stent implanted >12 months before surgery, old-generation drug-eluting stent was associated with higher risk of events at any time point. Conversely, new-generation drug-eluting stent showed similar safety as bare-metal stent >12 months and between 6 and 12 months and appeared trendly safer between 0 and 6 months.

Conclusions—

Surgery is frequent in patients with coronary stents and carries a considerable risk of ischemic and bleeding events. Ischemic risk is inversely related with time from percutaneous coronary intervention to surgery and is influenced by stent type.
Selective Blockade of Periostin Exon 17 Preserves Cardiac Performance in Acute Myocardial Infarction
Authors: Taniyama Yoshiaki , Katsuragi Naruto , Sanada Fumihiro , Azuma Junya , Iekushi Kazuma , Koibuchi Nobutaka , Okayama Keita , Ikeda-Iwabu Yuka , Muratsu Jun , Otsu Rei , Rakugi Hiromi , Morishita Ryuichi
Published: December 2015

We previously reported that overexpression of full-length periostin, Pn-1, resulted in ventricular dilation with enhanced interstitial collagen deposition in a rat model. However, other reports have documented that the short-form splice variants Pn-2 (lacking exon 17) and Pn-4 (lacking exons 17 and 21) promoted cardiac repair by angiogenesis and prevented cardiac rupture after acute myocardial infarction. The apparently differing findings from those reports prompted us to use a neutralizing antibody to selectively inhibit Pn-1 by blockade of exon 17 in a rat acute myocardial infarction model. Administration of Pn neutralizing antibody resulted in a significant decrease in the infarcted and fibrotic areas of the myocardium, which prevented ventricular wall thinning and dilatation. The inhibition of fibrosis by Pn neutralizing antibody was associated with a significant decrease in gene expression of fibrotic markers, including collagen I, collagen III, and transforming growth factor-β1. Importantly, the number of α-smooth muscle actin–positive myofibroblasts was significantly reduced in the hearts of animals treated with Pn neutralizing antibody, whereas cardiomyocyte proliferation and angiogenesis were comparable in the IgG and neutralizing antibody groups. Moreover, the level of Pn-1 expression was significantly correlated with the severity of myocardial infarction. In addition, Pn-1, but not Pn-2 or Pn-4, inhibited fibroblast and myocyte attachment, which might account for the cell slippage observed during cardiac remodeling. Collectively, these results indicate that therapeutics that specifically inhibit Pn exon-17, via a neutralizing antibody or drug, without suppressing other perisotin variants might offer a new class of medication for the treatment of acute myocardial infarction patients.