bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating antiretinal antibodies predict the outcome of anti‐VEGF therapy in patients with exudative age‐related macular degeneration
Authors: Kubicka‐Trząska Agnieszka , Wilańska Joanna , Romanowska‐Dixon Bożena , Sanak Marek
Published: August 2011

Purpose:  To determine serum antiretinal antibody (ARA) levels in response to treatment with intravitreal bevacizumab of exudative age‐related macular degeneration (AMD).

Methods:  The study comprised 22 patients treated with intravitreal bevacizumab (Avastin) 1.25 mg. In all patients, serum ARA levels were assessed by indirect immunofluorescence on normal monkey retina substrate. The ophthalmic examination including best corrected visual acuity (BCVA), fundoscopy, fluorescein angiography, optical coherence tomography (OCT) and immunohistochemical investigations. These were repeated at 4‐week intervals during a loading phase of antiangiogenic therapy. Sera of 22 sex‐ and age‐matched healthy subjects were used as controls for immunohistochemical studies.

Results:  Before bevacizumab therapy, ARAs were detected in the sera of all patients at titres ranging from 1:40 to 1:1280. The titres were significantly higher (p < 0.01) than in controls (1:10–1:40). There was no significant correlation between serum ARA titres and neither the type nor the dimensions of choroidal neovascularization, as well as central retinal thickness. Following treatment, all patients demonstrated significant decrease in ARA levels. This correlated with improvement of BCVA, decreased leakage of fluorescein and reduction of subretinal fluid on OCT.

Conclusion:  Serum ARA levels demonstrate a dynamic change which occurs in parallel with clinical outcomes of antiangiogenic therapy. They also may act as markers of the therapeutic benefits of vascular endothelial growth factor inhibition.
The rediscovery of Albuca tenuifolia, an orophilous species from the eastern Great Escarpment in South Africa
Authors: Martínez‐Azorín Mario , Clark Vincent R. , Crespo Manuel B. , Dold Anthony P. , Barker Nigel P.
Published: August 2011

Albuca tenuifolia Baker was described and illustrated in 1872 from South African material sent by Peter MacOwan to William Wilson Saunders in England, without a precise locality. Since then this species has been cited in later works although with many uncertainties. In addition, no type has been designated for this taxon. After field work in the Great Escarpment in South Africa, some populations of A. tenuifolia have been rediscovered growing in rocky places at high altitude. Data on morphology, ecology, and distribution are reported, and a lectotype and epitype are designated to fix the use of the name. Affinities with other species are also discussed.
Stipa×brozhiana (Poaceae) nothosp. nov. from the western Pamir Alai Mts (middle Asia) and taxonomical notes on Stipa×tzvelevii
Authors: Nobis Marcin
Published: August 2011

Stipa ×brozhiana M. Nobis nothosp. nov. (Poaceae) is described and illustrated. The taxon belongs to sect. Smirnovia Tzvel. and originated from the hybridization of species belonging to sect. Smirnovia and Barbatae Junge. Stipa ×brozhiana is morphologically close to Stipa lipskyi Roshev., but is easily distinguished by its much shorter hairs on the seta, thinner, uni‐ or indistinctly bigeniculate awns, differently shaped callus and longer ligules of vegetative shoots. Characters distinguishing S. ×brozhiana from the parental species and other similar hybrid taxa belonging to sect. Smirnovia and occurring in the Pamir Alai Mts are discussed. In addition, the taxonomical status of S. ×tzvelevii Ikonn. pro sp., another taxon that has originated from hybridization between species belonging to sect. Smirnovia and Barbatae, is discussed. The taxon was originally described as a distinct species, but is now considered to be the hybrid S. caucasica×S. orientalis. The main characters distinguishing S. ×tzvelevii from parental species are given.
Lasianthus chowdheryi sp. nov. (Rubiaceae) from Andaman and Nicobar Islands, India
Authors: Karthigeyan K. , Jayanthi J. , Sumathi R.
Published: August 2011

A new species, Lasianthus chowdheryi Karthig., Jayanthi & Sumathi (Rubiaceae), growing in the evergreen forest of Rutland Island in the Andaman and Nicobar archipelago is described. The new species is allied to L. attenuatus Jack, but differs by having tetramerous flowers, smaller corolla tube and by the presence of a horny appendage on the calyx and corolla apices. Detailed description and illustration of this new taxon are provided.
Aletris simpliciflora sp. nov. (Nartheciaceae) from southwest Xizang, China
Authors: Li Rong , Zhang Shu‐Dong
Published: August 2011

Aletris simpliciflora R. Li & S. D. Zhang, a new species of Nartheciaceae from southwest Xizang, China, is described and illustrated. It is similar, and apparently closely related, to A. nana S. C. Chen, but differs by having usually solitary flower, pubescent bract and bracteole, and distinct filaments ca 1.2 mm long.
Dementia in Chinese populations: Current data and future research
Authors: Feng Lei , Chiu Helen , Chong Mian‐Yoon , Yu Xin , Kua Ee‐Heok
Published: August 2011

This review summarizes the literature on the prevalence and incidence rates of dementia in Chinese populations, including survey results outside mainland China. We identified 15 prevalence studies and five incidence studies. The studies consistently reported sharply increased prevalence and incidence rates of dementia with increasing age. As estimated, there are at least 6,464,040 dementia patients in mainland China alone and we expect the number to rise in the coming decades. It is clear that dementia will be a new epidemic of the 21st century without major public health policies and preventive measures that target at the disease. We urge more research and hope that we will be able to prevent dementia or at least delay the onset in the near future with evidence‐based measures.
Surgical management of locoregionally recurrent thymoma
Authors: Park Byungjoon , Park Joon Suk , Kim Hong Kwan , Choi Yong Soo , Kim Kwhanmien , Shim Young Mog , Kim Jhingook
Published: August 2011

Objectives:  There is no standard treatment for recurrent thymoma, but treatment is usually palliative therapy. For this article, we retrospectively reviewed our experiences to examine the efficacy of surgical treatment and the extent of adequate resection.

Methods:  From 1997 to 2007, 15 patients underwent surgical resection for locoregional recurrence of thymoma in the Samsung Medical Center. The tumors at the initial resection were B1 in two patients, B2 in six, B3 in three and C in four according to the World Health Organization histological classification. Complete resection was achieved in 12 patients with pleurectomy (n = 11) or extrapleural pneumonectomy (n = 1).

Results:  There was neither perioperative mortality nor significant immediate postoperative morbidity. After discharge, chest computed tomography scans were evaluated after a minimum of 6 months and the median follow‐up duration was 45 months. At the time of writing, 10 patients had survived with (n = 5) or without (n = 5) rerecurrence (3‐year survival = 84.0%). Survival was significantly superior in patients with complete resection compared with those with incomplete resection (P= 0.008).

Conclusions:  Surgical resection could be considered in patients with locoregionally recurrent thymoma because it can be performed safely and offers a chance of long‐term survival to some patients. To achieve complete resection, more extended surgery must be considered for multiple pleural metastases.
Early detection of interstitial pneumonia by monitoring KL‐6 in a chronic hepatitis C patient undergoing pegylated interferon and ribavirin therapy
Authors: Ichikawa‐Yamada Yuki , Joshita Satoru , Tsukahara Yoshinori , Kimura Takefumi , Morita Susumu , Kamijo Atsushi , Umemura Takeji , Ichijo Tetsuya , Matsumoto Akihiro , Yoshizawa Kaname , Tanaka Eiji
Published: August 2011

A 58‐year‐old woman with chronic hepatitis C developed interstitial pneumonia (IP) while undergoing pegylated interferon (PEG IFN)‐α‐2a and ribavirin (RBV) therapy. Serum levels of sialylated carbohydrate antigen KL‐6 (KL‐6), a known marker of disease activity in fibrosing lung disorders, had been regularly measured once a month for early detection of IP, and had begun rising noticeably from 12 weeks to 540 U/mL at 33 weeks of treatment. On examination, remarkable fine crackles were detected by dorsal auscultation and bilateral ground‐glass opacities and reticular shadows were depicted by computed tomography. The patient successfully recovered from her early‐stage pneumonia by immediate discontinuation of therapy, which indicates that regular monitoring of serum KL‐6 may be effective for avoidance of IP progression induced by PEG IFN and RBV therapy.
Primary biliary cirrhosis – Autoimmune hepatitis overlap syndrome: A rationale for corticosteroids use based on a nation‐wide retrospective study in Japan
Authors: Tanaka Atsushi , Harada Kenichi , Ebinuma Hirotoshi , Komori Atsumasa , Yokokawa Junko , Yoshizawa Kaname , Abe Masanori , Miyake Yasuhiro , Kikuchi Kentaro , Ohira Hiromasa , Zeniya Mikio , Yamamoto Kazuhide , Ishibashi Hiromi , Onji Morikazu , Nakanuma Yasuni , Tsubouchi Hirohito , Takikawa Hajime
Published: August 2011

Aims:  Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) may simultaneously coexist in some patients, designated as PBC‐AIH overlap syndrome. Previous studies suggest that combination therapy of ursodeoxycholic acid (UDCA) and corticosteroids may be effective. In the current study, we aimed to describe clinical features of these cases and to propose a rationale for combination treatment in PBC‐AIH overlap.

Methods:  We enrolled patients with PBC‐AIH overlap from eight referral centers for liver diseases in Japan, and clinical, biochemical and immunological features were examined. Liver histology of all patients at diagnosis were analyzed altogether in detail. Eighty‐nine and 44 patients with PBC and AIH alone were included and served as controls.

Results:  We identified 33 patients with PBC‐AIH overlap. The mean follow‐up period was 6.1 years. On liver histology, the HA (hepatitis activity) score was significantly higher than the CA (cholangitis activity) score (P < 0.001). At the end of the follow‐up period, corticosteroids were used in 23 patients (72%), and neither liver‐related death nor liver transplantation had been noted. The sensitivity and specificity of the simplified AIH scoring system for prediction of patients who required corticosteroids during clinical course was 92% and 75% in the training set (n = 17), and 91% and 80% in the validation set (n = 16) of overlap. Only 3% of PBC patients were diagnosed as having indication for corticosteroid use.

Conclusion:  In PBC‐AIH overlap, AIH‐like features are dominant in liver histology. The simplified AIH scoring system could predict patients who needed corticosteroids with a higher specificity.
Digging in, Spreading out and Growing up: Introducing CLTS in Africa
Authors: Kar Kamal , Milward Kirsty
Published: August 2011

Open defecation is the norm in rural and urban Africa – only about a third of the population uses improved sanitation facilities – and this contributes in various ways to a heavy disease burden. Community‐led Total Sanitation (CLTS), an approach to sanitation which focuses on community‐wide behaviour change to completely stop open defecation, began to go to scale in Africa in 2006. Since then, it has spread dramatically and in many countries very successfully, and is now used at some level in at least 26 African countries.

This paper draws on the extensive involvement of Kamal Kar with the spread of CLTS in Africa to describe the early stages of the process, to elaborate on its developments and to outline insights into the circumstances and features which have facilitated its rapid spread. Taking a broadly comparative approach which draws on the somewhat earlier experience of the spread of CLTS in Asia, it identifies aspects of the institutionalisation process and circumstances, including key individuals, that have contributed to the success of the approach in Africa. It also discusses challenges, however, noting several issues which may limit its impact and hinder its dissemination. In particular, the paper discusses some of the many adaptations made to CLTS in response to a wide range of pressures, varying country circumstances and strategy choices. These adaptations, it is claimed, should be made with a clear picture of what may be lost and gained by adopting them. As CLTS progresses further, it will be important to continue to grapple with these issues, to acknowledge the lessons from adaptations that have had little success, and to retain a vision of the potential of CLTS to bring fundamental transformations in sanitation, health and rural lives.
When can we ignore the problem of imperfect detection in comparative studies?
Authors: Archaux Frédéric , Henry Pierre‐Yves , Gimenez Olivier
Published: August 2011

1. Numbers of individuals or species are often recorded to test for variations in abundance or richness between treatments, habitat types, ecosystem management types, experimental treatments, time periods, etc. However, a difference in mean detectability among treatments is likely to lead to the erroneous conclusion that mean abundance differs among treatments. No guidelines exist to determine the maximum acceptable difference in detectability.

2. In this study, we simulated count data with imperfect detectability for two treatments with identical mean abundance (N) and number of plots (nplots) but different mean detectability (p). We then estimated the risk of erroneously concluding that N differed between treatments because the difference in p was ignored. The magnitude of the risk depended on p, N and nplots.

3. Our simulations showed that even small differences in p can dramatically increase this risk. A detectability difference as small as 4–8% can lead to a 50–90% risk of erroneously concluding that a significant difference in N exists among treatments with identical N = 50 and nplots = 50. Yet, differences in p of this magnitude among treatments or along gradients are commonplace in ecological studies.

4. Fortunately, simple methods of accounting for imperfect detectability prove effective at removing detectability difference between treatments.

5. Considering the high sensitivity of statistical tests to detectability differences among treatments, we conclude that accounting for detectability by setting up a replicated design, applied to at least part of the design scheme and analysing data with appropriate statistical tools, is always worthwhile when comparing count data (abundance, richness).
Paraneoplastic manifestations of cancer in horses
Authors: Axiak S. , Johnson P. J.
Published: August 2011

Paraneoplastic manifestations of cancer, probably under‐recognised in equine clinical practice, are often observed before the underlying primary disease is identified. This review provides a summary of paraneoplastic phenomena that have been reported in horses. The inclusion of paraneoplastic explanations in the differential diagnosis of common and challenging clinical problems should lead to earlier diagnosis and greater chance for successful therapeutic outcomes. In some cases, alterations in the clinical severity of paraneoplastic signs can be used as indicators of disease progression or response to treatment.
Rearrangement of energetic and substrate utilization networks compensate for chronic myocardial creatine kinase deficiency
Authors: Dzeja Petras P. , Hoyer Kirsten , Tian Rong , Zhang Song , Nemutlu Emirhan , Spindler Matthias , Ingwall Joanne S.
Published: August 2011

Non‐Technical Summary  Continuous and vigorous heart work is powered by the energetic grid consisting of mitochondria, miniature ATP‐generating fuel cells, and molecular connecting circuits transferring and distributing high‐energy phosphoryls. The creatine kinase (CK) phosphotransfer circuit is the major component of the energetic network, coupling mitochondria with ATP utilization sites, and CK deficiency is a hallmark of cardiovascular diseases. Identification of mechanisms that compensate for reduced CK function would foster approaches leading to recovery and repair of injured hearts. Here, using advanced stable isotope metabolic technologies, we demonstrate that genetic CK deficiency induces a shift in heart energy distribution and substrate utilization networks by redirecting phosphotransfer flux through alternative adenylate kinase, glycolytic and guanine nucleotide systems. Such energetic re‐wiring, together with increased mitochondrial and glycolytic capacities, defines an adaptive metabolomic phenotype of CK deficiency. These findings advance our understanding of cellular energetic infrastructure and provide new perspectives for regulation of energy distribution in disease states.
Why Do Influenza Virus Subtypes Die Out? A Hypothesis
Authors: Palese Peter , Wang Taia T.
Published: August 2011

Novel pandemic influenza viruses enter the human population with some regularity and can cause disease that is severe and widespread. The emergence of novel viruses, historically, has often been coupled with the disappearance of existing seasonal virus strains. Here, we propose that the elimination of seasonal strains during virus pandemics is a process mediated, at the population level, by humoral immunity. Specifically, we suggest that infection with a novel virus strain, in people previously exposed to influenza viruses, can elicit a memory B cell response against conserved hemagglutinin stalk epitopes and/or neuraminidase epitopes. The anti-stalk and/or anti-neuraminidase antibodies then act to diminish the clinical severity of disease caused by novel influenza viruses and to eliminate seasonal virus strains.
Postoperative management of gastrointestinal cases
Authors: Charlesworth Tim
Published: August 2011

Small animals that have undergone surgery of the gastrointestinal tract can all too easily deteriorate and succumb to potentially devastating complications if their postoperative care is inadequate. Veterinary surgeons therefore need to pay just as much attention to the postoperative phase of patient management as to the preoperative and intraoperative phases. This article describes the normal physiology and healing of the gastrointestinal tract, and discusses the provision of analgesia and intravenous fluid support for patients following gastrointestinal surgery. A second article, to be published in the October issue of In Practice, will outline the nutritional requirements of these animals, and consider the appropriate use of antibiotics as well as the need for active monitoring for postoperative complications.
Role of the veterinary surgeon in managing the impact of dairy farming on the environment
Authors: Green Martin , Husband James , Huxley Jon , Statham Jonathan
Published: August 2011

With increasing concerns surrounding the causes and consequences of climate change, the impact of agriculture on the environment has come under intense scrutiny. For example, it is claimed that the livestock sector produces 18 per cent of all worldwide greenhouse gas emissions (measured in carbon dioxide equivalents), which, on a global basis, equates to more than all means of transport. It is therefore important to consider changes to farming systems and management methods that could reduce negative environmental effects. It is likely that pressure will mount on agriculture to proportionally reduce its emissions in line with other industries in order to meet government targets on greenhouse gas emissions. However, controversy remains over which farming methods result in the best environmental outcomes and there are also potential areas of conflict between environmental issues and animal health/welfare considerations or perceptions. This article considers the role of the veterinary surgeon in mitigating some of the potentially harmful effects of dairy farming on the environment.
INFLUENCE OF DEFECT STRUCTURE ON CATALYTIC ACTIVITY OF NANOMETRIC MATERIALS BASED ON CERIA-DOPED COPPER
Authors: ZAITZ MAŁGORZATA M. , MOLENDA MARCIN , CHMIELARZ LUCJAN , PIWOWARSKA ZOFIA , DUDEK BARBARA , WALAS STANISŁAW , DZIEMBAJ ROMAN
Published: August 2011

A series of nanometric materials based on copper-doped cerium (IV) oxide was synthesized using a reverse (w/o) microemulsion method. The obtained powder precursors were tested by the thermal analysis methods coupled with evolved gas analysis (EGA-TGA/DTG/SDTA). Morphology and structure of the samples were characterized by XRD and BET analysis. The content of copper ions was determined using a ICP-OES spectrometer. The electronic structure of the catalysts was characterized by high-temperature electrical conductivity measurements at different pO 2. The obtained materials were tested in catalytic incineration of the selected VOCs (methanol and ethylene). The correlation between the activity of the catalysts and copper content as well as electrical properties has been confirmed.
EVOLUTION OF MICROSTRUCTURE AND PHASE COMPOSITION UPON ANNEALING OF LiFePO4 PREPARED BY A LOW TEMPERATURE METHOD
Authors: ZAJAC W. , MARZEC J. , MAZIARZ W. , RAKOWSKA A. , MOLENDA J.
Published: August 2011

The effect of annealing of nanosized LiFePO 4 powder on microstructure, phase composition, iron valence state and electrical conductivity has been studied. Careful microstructural characterization of the as-prepared powder using high resolution TEM revealed presence of {010}-type crystal planes at the surface of crystallites, which seem to be beneficial to electrochemical activity. The second part of the work is focused on explanation of presence and evolution of Fe 3+ detected in the material. Transmission and CEMS modes of Mössbauer spectroscopy together with TEM allowed for ruling out concept of amorphous layers containing Fe 3+ ions covering crystalline LiFePO 4 grains.
HETERO-JUNCTION COMPOSED OF POLY(3, 4-ETHYLENEDIOXYTHIOPHENE) WITH POLY(STYRENESULPHONATE) AND IODINE DOPED TITANIUM DIOXIDE
Authors: SIUZDAK KATARZYNA , LISOWSKA-OLEKSIAK ANNA
Published: August 2011

This work presents new bulk p-n hetero-junction where iodine doped TiO 2 ( I-TiO 2) acts as n and poly(3, 4-ethylenedioxy- thiophene):polystyrenesulphonate (pEDOT:PSS) as p-element. Heterogeneous films were obtained by means of potentiostatic polymerization of monomer on the metal electrode in presence of suspended I - TiO 2 particles in the electrolyte, (applied potentials in a range of 0.8–1.1 V versus Ag/AgCl/0.1 M KCl ). The procedure brings about hybrid films where I - TiO 2 particles are uniformly incorporated into the bulk polymer matrix. An incorporation of I - TiO 2 into the pEDOT:PSS matrix causes increase in the measured current under visible light illumination.
CHARACTERIZATION OFPt–Rh–RuCATALYSTS FOR METHANOL OXIDATION
Authors: CHOTKOWSKI MACIEJ , UKLEJEWSKA MONIKA , SIWEK HANNA , DŁUBAK JUSTYNA , CZERWIŃSKI ANDRZEJ
Published: August 2011

Pt – Rh – Ru alloy catalysts for methanol electro-oxidation were prepared by electrochemical deposition under constant potential conditions. The Pt : Rh : Ru ratio was varied by changing electroplating solution composition. Obtained catalysts were examined electrochemically in acidic solutions containing methanol. Stripping voltammetry was applied to study adsorption of methanol on the electrodes surfaces while oxidation of methanol from solution was studied by means of chronoamperometry and cyclic voltammetry. The highest electrocatalytic activity was observed for an alloy with the highest obtained ruthenium concentration of 31%.
NICKEL-BASED LAYERED PEROVSKITE CATHODE MATERIALS FOR APPLICATION IN INTERMEDIATE-TEMPERATURE SOLID OXIDE FUEL CELLS
Authors: HAN JUAN , ZHENG KUN , ŚWIERCZEK KONRAD
Published: August 2011

In this work we present results of structural (XRD) and microstructural (SEM) characterization, as well as determination of transport properties (electrical conductivity, Seebeck coefficient) and oxygen nonstoichiometry as a function of temperature for La 2 NiO 4+δ, Nd 2 NiO 4+δ and Pr 2 NiO 4+δ layered perovskites, promising cathode materials for application in intermediate-temperature solid oxide fuel cells (IT-SOFCs). In addition to characterization of physico-chemical properties, the obtained materials were used as cathodes in custom made, electrolyte-supported IT-SOFCs. Electrochemical performance and impedance spectroscopy (EIS) measurements were performed on the cells in 600–850°C temperature range. The obtained maximum power densities, exceeded 0.2 W⋅cm-2 at 800°C.
ELECTROCHEMICAL ACTIVITY OF COMPOSITE MATERIAL POLY(3, 4-ETHYLENEDIOXYTHIOPHENE) MODIFIED BY SILVER HEXACYANOFERRATE
Authors: NOWAK ANDRZEJ P. , LISOWSKA-OLEKSIAK ANNA
Published: August 2011

An electrochemical way to prepare poly(3, 4-ethylenedioxythiophene) (pEDOT) modified by silver hexacyanoferrate (Aghcf) is presented. The electrode material is synthesized in two-stage procedure. The first stage is galvanic silver electrodeposition on a glassy carbon substrate electrode. The second step is silver stripping followed by Aghcf formation during monomer oxidation. Deposited composite layer is compact but not homogenous in a micro-scale. The low spin iron centre redox activity depends on a kind of the electrolyte. Potassium and nitrate ions are the most suitable for redox couple reversibility. The redox activity diminishes in contact with electrolytes in series KNO 3 > K 2 SO 4 > KBr . In the presence of chloride ions redox activity of silver hexacyanoferrate is inhibited. Spectroelectrochemical measurements proved electrochromic character of the film.
DSC AND ELECTRICAL CONDUCTIVITY STUDIES ON SUPERIONIC ALL-GLASS PHOSPHATE-BASED COMPOSITES
Authors: NOWIŃSKI JAN L. , ŚLUBOWSKA WIOLETA , GARBARCZYK JERZY E. , WASIUCIONEK MAREK
Published: August 2011

The work investigates electrical properties of all-glass composite Ag +-ion conductors based on silver phosphate glasses. A combination of X-ray diffraction (XRD) and differential scanning calorimetry (DSC) was used for characterization of the samples. The impedance spectroscopy (IS) was applied to determine the electrical conductivity in a wide temperature range (from -140 to +20°C). Results of the DSC studies indicate that all-glass materials prepared from the powdered glasses are bi-phasic. On the other hand their electrical properties resemble homogeneous rather than heterogeneous superionic conductors.
THE ROLE OF INTERMEDIATE CALCIUM ALUMINATE PHASES IN SOLID STATE SYNTHESIS OF MAYENITE (Ca12Al14O33)
Authors: RUSZAK M. , WITKOWSKI S. , PIETRZYK P. , KOTARBA A. , SOJKA Z.
Published: August 2011

Structural transformations during the synthesis of mayenite ( Ca 12 Al 14 O 33) were investigated. The samples were prepared by a solid–state reaction and the transformations were researched by means of XRD, Rietveld analysis, SEM, and Raman spectroscopy. The three key phases ( CaAl 2 O 4, Ca 3 Al 2 O 6, Ca 5 Al 6 O 14) were identified and their role in the mayenite formation was assigned. The optimal low temperature pathway of the mayenite synthesis involving Ca 5 Al 6 O 14 intermediate was proposed.
MODIFICATION OF BaCeO3 PROTONIC CONDUCTORS BY Ag AND Y DOPING
Authors: OSIADŁY MAGDALENA , PASIERB PAWEŁ , KOMORNICKI STANISŁAW , RȨKAS MIECZYSŁAW
Published: August 2011

Silver and yttrium dopants influence some physico-chemical properties of BaCeO 3 protonic conduction. Ag -acceptor dopant substituting Ba atom in BaCeO 3 compounds was studied for the first time. Ba 1-x Ag x Ce 1-y Y y O 3-δ (0 ≤ x ≤ 0.1, 0 ≤ y ≤ 0.1) materials were synthesized by solid state reaction and by modified Pechini citric acid method. X-ray diffraction (XRD) and electrical properties measurements including open cell voltage (OCV) of electrochemical cells were used as experimental techniques. Basing on XRD results it was found that all synthesized materials crystallized in orthorhombic Pnma phase with some admixtures of other phases. Metallic Ag , CeO 2 or Y 2 O 3 with different concentrations were detected, depending on the composition, synthesis method and preparation details. DC electrical measurements showed that doping by Ag and Y decreased the total and ionic conductivities of the materials. The modification of charge transport properties was also observed, namely introduction of Ag led to the increase of electronic component of total electrical conductivity, especially at higher temperatures.
Sunitinib induces apoptosis in pheochromocytoma tumor cells by inhibiting VEGFR2/Akt/mTOR/S6K1 pathways through modulation of Bcl-2 and BAD
Authors: Saito Yuria , Tanaka Yuko , Aita Yuichi , Ishii Kiyo-aki , Ikeda Tatsuhiko , Isobe Kazumasa , Kawakami Yasushi , Shimano Hitoshi , Hara Hisato , Takekoshi Kazuhiro
Published: August 2011

Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity that mainly targets vascular endothelial growth factor receptors (VEGFRs). Very recently, sunitinib has been shown to be an active agent for the treatment of malignant pheochromocytomas. However, it is unclear whether sunitinib acts only through an antiangiogenic mechanism or whether it may also directly target tumor cells. Sunitinib markedly induced apoptosis of PC12 cells in a dose-dependent and time-dependent manner. Furthermore, in support of these findings, we found that sunitinib induced a reduction in the expression of the antiapoptotic molecule Bcl-2 as well as dephosphorylation of the proapoptotic molecule BAD, which results in the activation of BAD in these cells. Consistent with these apoptotic effects, our results showed that sunitinib inhibited phosphorylation of Akt and mTOR and was followed by a reduction of S6K1, which is a well-known target of mTOR. Knockdown of VEGFR-2 attenuated the sunitinib-induced effects, including apoptosis and inhibition of signaling pathways such as the phosphorylation of Akt as well as mTOR, and Bcl-2, which confirmed that these effects could be mediated by VEGFR-2. In addition, silencing of S6K1 induced apoptosis accompanied by a decrease in the phosphorylation of BAD and Bcl-2, similar to that observed with sunitinib treatment. Thus, these results together suggest that sunitinib initially exerts its apoptotic effect through the inhibition of VEGFR-2, which, when followed by reduction of its downstream effectors, including Akt/mTOR/S6K1, may lead to inhibition of the antiapoptotic molecule Bcl-2 and activation of the proapoptotic molecule BAD in PC12 cells. However, PC12 cells do not precisely reflect the pathogenesis of malignant cells. Therefore, we confirmed the key findings by replicating these experiments in human neuroblastoma SK-N-SH cells.
TLR9 Agonists Oppositely Modulate DNA Repair Genes in Tumor versus Immune Cells and Enhance Chemotherapy Effects
Authors: Sommariva Michele , De Cecco Loris , De Cesare Michelandrea , Sfondrini Lucia , Ménard Sylvie , Melani Cecilia , Delia Domenico , Zaffaroni Nadia , Pratesi Graziella , Uva Valentina , Tagliabue Elda , Balsari Andrea
Published: August 2011

Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models. We hypothesized that the success of these combinations is related to the ability of CpG-ODN to modulate genes involved in DNA repair. We conducted an in silico analysis of genes implicated in DNA repair in data sets obtained from murine colon carcinoma cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN significantly increased the life span of mice compared with individual treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well as anthracycline-treated patients with breast cancer who are classified as “CpG-like” for the level of expression of CpG-ODN modulated DNA repair genes have a better outcome than patients classified as “CpG-untreated-like,” indicating the relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken together, the findings provide evidence that the tumor microenvironment can sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the benefits of CpG-ODN therapy beyond induction of a strong immune response. Cancer Res; 71(20); 6382–90. ©2011 AACR.
Antiangiogenic Agent Sunitinib Transiently Increases Tumor Oxygenation and Suppresses Cycling Hypoxia
Authors: Matsumoto Shingo , Batra Sonny , Saito Keita , Yasui Hironobu , Choudhuri Rajani , Gadisetti Chandramouli , Subramanian Sankaran , Devasahayam Nallathamby , Munasinghe Jeeva P. , Mitchell James B. , Krishna Murali C.
Published: August 2011

Structural and functional abnormalities in tumor blood vessels impact the delivery of oxygen and nutrients to solid tumors, resulting in chronic and cycling hypoxia. Although chronically hypoxic regions exhibit treatment resistance, more recently it has been shown that cycling hypoxic regions acquire prosurvival pathways. Angiogenesis inhibitors have been shown to transiently normalize the tumor vasculatures and enhance tumor response to treatments. However, the effect of antiangiogenic therapy on cycling tumor hypoxia remains unknown. Using electron paramagnetic resonance imaging and MRI in tumor-bearing mice, we have examined the vascular renormalization process by longitudinally mapping tumor partial pressure of oxygen (pO2) and microvessel density during treatments with a multi-tyrosine kinase inhibitor sunitinib. Transient improvement in tumor oxygenation was visualized by electron paramagnetic resonance imaging 2 to 4 days following antiangiogenic treatments, accompanied by a 45% decrease in microvessel density. Radiation treatment during this time period of improved oxygenation by antiangiogenic therapy resulted in a synergistic delay in tumor growth. In addition, dynamic oxygen imaging obtained every 3 minutes was conducted to distinguish tumor regions with chronic and cycling hypoxia. Sunitinib treatment suppressed the extent of temporal fluctuations in tumor pO2 during the vascular normalization window, resulting in the decrease of cycling tumor hypoxia. Overall, the findings suggest that longitudinal and noninvasive monitoring of tumor pO2 makes it possible to identify a window of vascular renormalization to maximize the effects of combination therapy with antiangiogenic drugs. Cancer Res; 71(20); 6350–9. ©2011 AACR.
From Targets to Treatments: A Review of Molecular Targets in Pancreatic Neuroendocrine Tumors
Authors: Wiedenmann Bertram , Pavel Marianne , Kos-Kudla Beata
Published: August 2011

Pancreatic neuroendocrine tumors (pancreatic NET) are relatively rare, slowly growing tumors, although their incidence is increasing, and patients may survive for several years with metastatic disease. Apart from symptomatic relief, there have been few treatment options for these tumors in the past. More recently, investigators have explored the potential of molecularly targeted agents in treating pancreatic NET, with some success. In this review, we consider the data supporting exploitation of different targets in pancreatic NET, including peptide receptors, receptor tyrosine kinases (involved in tumor angiogenesis and more directly supporting tumor growth), and intracellular targets, such as the mammalian target of rapamycin (mTOR), which has a central role in regulating cell growth, metabolism, and apoptosis. Probably due to the paucity of pancreatic NET, many clinical trials to date have included heterogeneous NET populations, and there are few randomized studies of this specific patient population. Very recently, promising results have been achieved in placebo-controlled, phase III trials with the multitargeted tyrosine kinase inhibitor, sunitinib, and the mTOR inhibitor, everolimus. These agents have been approved or are currently being reviewed by authorities for use in patients with pancreatic NET. Here we review potential molecular targets in pancreatic NET and summarize the available data for targeted agents from phase II and III trials open to patients with this tumor.
Dietary Restriction in Humans: A Response to Drs. Gavrilova and Gavrilov
Authors: Le Bourg Éric
Published: August 2011

In their response to my letter to the editor, Drs. Gavrilova and Gavrilov disagree with some of my arguments and argue that dietary restriction studies in humans ‘should not be dismissed as a valid tool to extending life span in non-obese individuals’. I would now like to answer their arguments and stress that studying dietary restriction in people with no health problems in the hope to increase their longevity is perhaps futile, but focusing studies in obese people bears the hope for more success in improving health in a significant part of the population.
Dose-dependent decrease of platelet activation and tissue factor by omega-3 polyunsaturated fatty acids in patients with advanced chronic heart failure
Authors: Berger Rudolf , Hammer Alexandra , Hutuleac Raisa , Koppensteiner Renate , Kopp Christoph , Steiner Sabine , Moertl Deddo
Published: August 2011

Chronic heart failure (CHF) is characterised by activation of neuroendocrine and inflammatory pathways, and both are linked to a prothrombotic state. Treatment with omega-3 polyunsaturated fatty acids (n3-PUFA) showed significant benefits including mortality reduction in CHF, but exact mechanisms of action are still unclear. We investigated the effects of n3-PUFA on markers of platelet activation and thrombogenesis in patients with severe CHF. Thirty-six patients with non-ischaemic CHF (LVEF<35%, NYHA class>2) under optimised therapy were randomised to supplementation with 1g/day or 4g/day n3-PUFA, or placebo for 12 weeks. Using whole-blood flow cytometry, monocyteplatelet aggregates characterised by CD14+/CD42b+ co-expression and monocytic tissue factor (TF) were determined. Plasma levels of P-selectin, sCD40L, fibrinogen, prothrombin fragment F1.2, TF and proinflammatory markers (high sensitive[hs] interleukin-6, hsCRP, hsTNFalpha, monocyte chemotactic protein-1) were measured by immunoassay. Supplementation with 1g/day and 4g/day n3-PUFA but not placebo significantly reduced monocyte-platelet aggregates in a dose-dependent manner (p for trend=0.02 across the groups). A dose of 4g/day but not 1g/day n3-PUFA significantly decreased P-selectin (p=0.03). Plasma TF decreased dose-dependently upon n3-PUFA supplementation (p for trend=0.02), paralleled by a significant decrease of TF+-monocytes (p for trend=0.01). The amount of 4g/day n3-PUFA exhibited modest anti-inflammatory effects with a significant reduction of hs interleukin-6 (p<0.01) and a trend-wise reduction of hsTNF-alpha (p=0.09). No changes were seen for sCD40L, fibrinogen, hsCRP and monocyte chemotactic protein-1, while F1.2 was decreased by 4g/day n3-PUFA (P=0.03). In patients with severe non-ischaemic CHF, treatment with n3-PUFA leads to a dose-dependent decrease of platelet activation and TF. Higher dosage exhibits also anti-inflammatory effects.

* ClinicalTrials.gov registration number: NCT00149409
Need + Prepositional Adverb in the Midland
Authors: Benson Erica J.
Published: August 2011

The status of the U.S. Midland as a separate dialect area has been a topic of discussion for quite some time, and Murray and Simon (2006b) strive for resolution by defining the Midland as a dialect area characterized by a core set of seventeen morpho-syntactic features that co-occur in the region but are not necessarily used by all or only Midlanders. In this article, the author argues that need + prepositional adverb (e.g., The dog needs out) belongs among the features of the Midland and presents data to show that this construction parallels the regional, social, and stylistic distributions of other Midland constructions. In addition, the author proposes that need + prepositional adverb has indirect links to Scotch-Irish English and is likely a U.S. or, at the very least, a recent innovation that arose by analogy to other Scotch-Irish features. Finally, need + prepositional adverb is a modern Midland feature that provides evidence against the Midland as simply a transition zone.
Randomized 5‐Treatment Crossover Study to Assess the Effects of External Heat on Serum Fentanyl Concentrations During Treatment With Transdermal Fentanyl Systems
Authors: Moore Kenneth T. , Sathyan Gayatri , Richarz Ute , Natarajan Jaya , Vandenbossche Joris
Published: August 2011

This randomized, open‐label, 5‐treatment, 5‐sequence crossover study was designed to evaluate the effects of a heating pad on serum fentanyl concentrations with reservoir and matrix transdermal fentanyl systems. Subjects were randomized to 1 of 5 treatment sequences, receiving 5 fentanyl treatments (1 per period) for 36 hours: 25 μg/h reservoir without heat, 25 μg/h reservoir with heat, 25 μg/h matrix without heat, 25 μg/h matrix with heat, and a 50 μg/h reservoir without heat. The 25 μg/h systems with heat had a heating pad applied from 0 to 10 and 26 to 36 hours post application. Washout periods between treatments were 5 to 14 days. Naltrexone was given to block the opioid effects of fentanyl. Study results indicate that external heat had a similar effect on both matrix and reservoir systems, with heat applied during the first 10 hours of treatment increasing fentanyl exposure by approximately 61% to 81% at 10 hours (observed serum concentration at 10 hours) and overall exposure (area under the curve from 0 to 10 hours) by approximately 120% to 184%, but had minimal effect from 26 to 36 hours. The increased exposure observed with heat in both 25 μg/h systems, between 0 and 10 hours, was higher than that obtained with the 50 μg/h reservoir system applied without heat.
Association Between Body Mass Index and Depressive Symptoms of African American Married Couples
Authors: Wickrama Thulitha , Bryant Chalandra M.
Published: August 2011

This study examined (a) associations between body mass index (BMI) and depressive symptoms in African American husbands and wives, (b) transactional associations between husbands and wives in this relationship, and (c) mediating and moderating role of couples’ behavioral closeness in this association. Data came from a sample of 450 African American married couples residing in a southern state. The study found that (a) husbands’ and wives’ BMI is positively associated with their own depressive symptoms, (b) only the wives’ BMI is positively associated with their partners’ depressive symptoms, (c) only the wives’ BMI is positively associated with their own and their partners’ depressive symptoms indirectly through couples’ behavioral closeness, and (d) among wives, the association between BMI and depressive symptoms is mediated and moderated by couples’ behavioral closeness. Family interventions need to increase indoor, outdoor, and intimate partner activities, thereby reducing the association between depressive symptoms and body weight for African American couples.
A Metabonomic Characterization of (+)-Usnic Acid-Induced Liver Injury by Gas Chromatography–Mass Spectrometry-Based Metabolic Profiling of the Plasma and Liver in Rat
Authors: Lu Xiaoyan , Zhao Qinqin , Tian Yu , Xiao Shun , Jin Tingting , Fan Xiaohui
Published: August 2011

Three doses of (+)-usnic acid (100, 200, and 240 mg/kg per d) were administered orally to Wistar rats for 8 days, and metabonomic characterization of (+)-usnic acid-induced liver injury based on gas chromatography–mass spectrometry metabolic profiles was evaluated. Serum biochemical analysis and histopathological examinations were simultaneously performed. The liver/body weight ratio was significantly increased in (+)-usnic acid-treated groups, whereas serum alanine aminotransferase and total bilirubin were significantly elevated. In liver sections of 200 and 240 mg/kg dosage groups, widespread hydropic degeneration of hepatocytes was observed. Clusters in partial least squares discriminant analysis score plots showed control and (+)-usnic acid-treated groups had an obvious separation. (+)-Usnic acid exposure can lead to disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, which may be attributable to (+)-usnic acid toxicological effects on the liver through oxidative stress. The significant changes in 22 metabolites in liver might be adopted as potential biomarkers.
A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols)
Authors: Notcutt W , Langford R , Davies P , Ratcliffe S , Potts R
Published: August 2011

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical.

Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal.

Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects’ previous effective and tolerated dose was continued.

Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex ( p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex.

Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.
Non-domination and pure negative liberty
Authors: Harbour Michael David
Published: August 2011

The central insights of Philip Pettit’s republican account of liberty are that (1) freedom consists in the absence of domination and (2) non-domination is not reducible to what is commonly called ‘negative liberty’. Recently, however, Matthew Kramer and Ian Carter have questioned whether the harms identified by Pettit under the banner of domination are not equally well accounted for by what they call the ‘pure negative’ view. In this article, first I argue that Pettit’s response to their criticism is problematic insofar as it produces the following dilemma: either Pettit must concede that domination which one regards as consistent with one’s own best interests does not limit one’s freedom or he must embrace the implication that one can be forced to be free, a result he explici tly wants to avoid. Second, I argue that, despite the inadequacy of Pettit’s response, he is ultimately right in thinking that domination and negative liberty are sometimes compatible. My central contention, then, is that neither Pettit’s non-domination view nor Carter and Kramer’s pure negative view are able to account for the loss of liberty one suffers under conditions of domination.