bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion
Authors: Yahalom-Ronen Yfat , Rajchman Dana , Sarig Rachel , Geiger Benjamin , Tzahor Eldad
Published: August 2015

Cardiomyocyte (CM) maturation in mammals is accompanied by a sharp decline in their proliferative and regenerative potential shortly after birth. In this study, we explored the role of the mechanical properties of the underlying matrix in the regulation of CM maturation. We show that rat and mouse neonatal CMs cultured on rigid surfaces exhibited increased myofibrillar organization, spread morphology, and reduced cell cycle activity. In contrast, compliant elastic matrices induced features of CM dedifferentiation, including a disorganized sarcomere network, rounding, and conspicuous cell-cycle re-entry. The rigid matrix facilitated nuclear division (karyokinesis) leading to binucleation, while compliant matrices promoted CM mitotic rounding and cell division (cytokinesis), associated with loss of differentiation markers. Moreover, the compliant matrix potentiated clonal expansion of CMs that involves multiple cell divisions. Thus, the compliant microenvironment facilitates CM dedifferentiation and proliferation via its effect on the organization of the myoskeleton. Our findings may be exploited to design new cardiac regenerative approaches.
Prevalence of venous ulcers and associated factors among adults of a health center in Vitória da Conquista – BA
Authors: Oliveira Shirley Batista , Soares Daniela Arruda , Pires Patrícia da Silva
Published: August 2015

Objetivo:Estimar a prevalência de úlceras venosas e identificar os fatores sociodemográficos, comportamentais, de saúde, características da ferida e tratamento associados entre indivíduos adultos atendidos em um Centro de Saúde de Vitória da Conquista – BA. Métodos: Trata-se de um estudo transversal no qual foram estudados 42 indivíduos. As análises estatísticas foram feitas no Epi Info versão 3.5.3. Resultados: A prevalência de úlceras venosas foi de 83,3%, sendo maior no sexo feminino (95,5%). Os fatores que se mantiveram associados foram o sexo, morar acompanhado, diabetes, insuficiência venosa crônica, presença de dor, tempo de inicio da primeira úlcera e reincidência da ferida. Conclusão: Os resultados sugerem a necessidade de novas pesquisas para melhorar os registros nacionais acerca das úlceras venosas e viabilizar estratégias que garantam uma melhor assistência a saúde baseada em evidências científicas e clínicas.
Delirium in the elderly in intensive care units: an integrative literature review
Authors: De Barros Marcia Abath Aires , De Oliveira Figueirêdo Danielle Samara Tavares , Fernandes Maria das Graças Melo , Ramalho Neto José Melquiades , Macêdo-Costa Kátia Neyla de Freitas
Published: August 2015

Objetivo: Realizar um levantamento acerca do delirium em idosos em Unidade de Terapia intensiva (UTI). Método: Revisão integrativa da literatura, nas bases de dados, MEDLINE e IBECS, em maio de 2012, cujos critérios de inclusão foram ser publicado entre maio de 2007 a maio de 2012, disponibilidade na íntegra e nos idiomas português, inglês e espanhol. Resultados: Foram encontrados 68 produções e selecionados 16, as quais foram categorizados em: 1) Incidência e prevalência de delirium em Idosos na UTI; 2) Fatores de risco precipitantes e predisponentes do delirium em idosos na UTI e 3) Estratégias de prevenção de fatores de risco modificáveis do delirium em idosos nas  UTIs. Conclusão: A produção científica acerca do delirium no Brasil é incipiente, os profissionais de saúde, especialmente da enfermagem, necessitam melhorar o reconhecimento desta síndrome e implementar estratégias de prevenção dos fatores de risco para delirium.
Strategies for joining to the treatment for seropositive pregnant women to human immunodeficiency virus
Authors: Pereira Fabiani Weiss , Kleinubing Raquel Einloft , Ilha Silomar , Gomes Giovana Calcagno , De Souza Michele Bulhosa
Published: August 2015

Objetivo: Identificar as estratégias que os profissionais utilizam para auxiliar na adesão ao tratamento de gestantes soropositivas para o Vírus da Imunodeficiência Humana. Métodos: Trata-se de uma pesquisa exploratória, descritiva de caráter qualitativo desenvolvida com dez profissionais que atuam em um Centro de Testagem e Aconselhamento no sul do Brasil. Os dados, coletados no período de maio de 2010 por meio de entrevistas semiestruturadas, foram submetidos à análise temática. Resultados: Os resultadosapontaram como estratégias ações de acolhimento, visando a inclusão dessas gestantes no serviço e a aproximação com a equipe; a realização de atividades grupais e a busca ativa das faltosas, respeitando sua autonomia e preservando seu sigilo.  Conclusão: Concluiu-se que para a adesão ao tratamento é necessário que a equipe esteja envolvida no atendimento de forma interdisciplinar, humanizada e qualificada, podendo o enfermeiro ser o articulador das ações. Descritores: HIV, Gestantes, Profissionais da saúde, Enfermagem.
An integrative review about the pediatric heart transplant and the aspects of quality of life
Authors: Di Carlantonio Lucilia Marques , Santiago Luiz Carlos , Ribeiro Renata Vitalino , Arcoverde Karla Valeria
Published: August 2015

Objetivo: Trata-se de uma revisão integrativa de literatura que objetiva revisar as produções referentes ao transplante cardíaco pediátrico e os aspectos na qualidade de vida, sintetizando o impacto do transplante neste grupo. Método: Revisão integrativa, onde foram eleitos descritores; testados combinações; realizada busca nas bases de dados e análise temática para examinar os achados. Resultados: Do recorte de 68 artigos pesquisados, foram selecionados 23, dentre eles apenas 10, se enquadravam em todos os critérios, e foram analisados. Conclusão: As cardiopatias congênitas complexas podem ser tratadas com o transplante cardíaco, em alguma fase de sua evolução, sem aumento da mortalidade ou morbidade, fato que evidenciamos nas complicações medicas passíveis de controle. Descritores: Qualidade de vida, Transplante de coração, Criança, Enfermagem.
Popular education in health with fishermen: an experience outside the nurse´s “comfort zone”
Authors: Batista Ribeiro Crystiane Ribas , Sabóia Vera Maria
Published: August 2015

O presente artigo reflete sobre uma atividade educativa participativa desenvolvida com um grupo de pescadores artesanais, de uma comunidade no município de São Gonçalo-Rio de Janeiro. Tal ação foi contextualizada por achados prévios relacionados à questões sócio-clínico-demográficas e poluição ambiental local. Participaram da atividade quatro pescadores, com tempo de pesca variando entre 2 e 20 anos. A atividade aconteceu no período da manhã no mês de julho, após a inserção da pesquisadora no cenário nos seis meses anteriores. Foram levantadas as principais dificuldades encontradas pelos pescadores na atividade pesqueira, dúvidas sobre problemas de saúde como hipertensão arterial e diabetes mellitus, ocorrência de feridas cutâneas e formas de tratamento, utilizando-se estratégia participativa associada a recursos didáticos. A experiência permitiu conhecer singularidades e desafios enfrentados pelo grupo. Ao final foi elaborado um banner contendo orientações educativas construídas com os pescadores. Descritores: Educação em Saúde, Grupos, Enfermagem.
Nursing interventions for children and adolescents with câncer during the chemotherapy treatment
Authors: Dos Santos Thaís Regina Araújo , De Souza Sônia Regina
Published: August 2015

RESUMO Objetivos: Identificar, a partir da produção científica, as ações de enfermagem para crianças e adolescentes durante o tratamento de quimioterapia; Classificar as ações de enfermagem, identificadas na literatura, de acordo com os domínios da Taxonomia NIC (Intervenções de Enfermagem); Compor um quadro referencial com as principais Intervenções de Enfermagem, segundo a Taxonomia NIC, para crianças e adolescentes durante o tratamento quimioterápico.  Métodos: Trata-se de uma revisão integrativa que tem o objetivo de identificar as intervenções de enfermagem à criança e ao adolescente com câncer durante o tratamento quimioterápico. Resultados: Foram identificadas dez ações de enfermagem. Estas foram classificadas de acordo com os domínios da Taxonomia NIC (Intervenções de Enfermagem). Conclusão:  A intervenção psicológica, o apoio dos profissionais e a presença da família junto à criança e/ou ao adolescente geram resultados positivos durante o tratamento e depois do fim do mesmo. O principal foco da presente pesquisa é mostrar que a assistência de enfermagem prestada às crianças e aos adolescentes com câncer não deve se limitar a atender somente o corpo biológico, mas também considerá-los como seres em crescimento e desenvolvimento. Descritores:  Assistência de Enfermagem, Criança/Adolescente, Quimioterapia.
Effect of liquid addition on the bulk and flow properties of fine and coarse glass beads
Authors: Scicolone James V. , Metzger Matthew , Koynov Sara , Anderson Kellie , Takhistov Paul , Glasser Benjamin J. , Muzzio Fernando J.
Published: August 2015

The effect of water on the packing and flow properties of fine and coarse particles was experimentally investigated. Four different particle sizes of glass beads, from 5 to 275 μm, were studied with increasing water weight‐percentages. Using a FT4 Powder Rheometer, changes in bulk properties were collected as a function of water content and particle size. The results show that water content plays a significant role on the packing and flow of the particles. Small amounts of water created porous aggregates due to liquid bridging. Greater amounts of water resulted in the filling of the void‐spaces. This was indicated by an increase in basic flow energy, density, and pressure drop, with a decrease in porosity. A greater understanding of bulk properties of wetted material is useful to develop standard systems that can be used to examine the behavior of more complex situations, and implement changes to improve materials handling and processing. © 2015 American Institute of Chemical Engineers AIChE J, 62: 648–658, 2016
Cervical spinal cord injuries associated with resuscitation from fatal circulatory collapse
Authors: Miyata Kei , Mikami Takeshi , Koyanagi Izumi , Mikuni Nobuhiro , Narimatsu Eichi
Published: August 2015

Introduction

Fatal cervical spinal cord injury (SCI) associated with collapse of the circulatory and/or respiratory system usually consists of high cervical SCI caused by high‐energy trauma. As the elderly population grows, however, the etiology of fatal SCI may be changing. The aim of the present study was to understand the current clinical features of fatal SCI.

Methods

Retrospective analysis was performed on 73 consecutive patients with acute cervical SCI between 2007 and 2013. Fourteen (19%) of them presented in a state of coma due to severe circulatory collapse after cardiac arrest (CA, n = 11) or respiratory arrest (RA, n = 3), and were resuscitated at the scene or hospital. The clinical features and radiological findings of these 14 patients were compared with those of the other 59.

Results

Eleven of the 14 fatal SCI patients were injured by minor traumas. Computed tomography revealed C1‐2 fractures or dislocations in 11 patients and subaxial injuries in three patients. Eleven patients showed some kind of ossification of the spinal column ligaments. In a univariate analysis, the predictive factors associated with fatal circulatory collapse were age (P = 0.02), estimated C1/2 injury (P < 0.0001), and complete tetraplegia (P < 0.0001). In a multiple regression model for fatality, the odds ratios (OR) for C1/2 injury and ASIA impairment score (AIS) A were 20.58 (P = 0.006) and 151.97 (P = 0.002).

Conclusions

A state of unconsciousness with fatal circulatory collapse was significantly associated with C1/2 injury and AIS A. Moreover, our data show that fatal SCI can occur due to minor trauma in elderly people.
Structure of Nanochannel Entrances in Stopcock‐Functionalized Zeolite L Composites
Authors: Tabacchi Gloria , Fois Ettore , Calzaferri Gion
Published: August 2015

Multifunctional hybrid materials are obtained by modifying zeolite L (ZL) with stopcock molecules, consisting of a tail group that can enter the ZL nanochannels and a head group too large to pass the channel opening. However, to date no microscopic‐level structural information on modified ZL materials has been reported. Herein we draw atomistic pictures of channel openings and stopcock‐functionalized ZL based on first‐principles calculations. We elucidate the interactions of the tail group with the inner surface of ZL channels and the space‐filling properties of the stopcocks, revealing cork‐ or lid‐sealing modes. Water is essential to obtain stable modifications. AlOH groups are the preferred modification sites, bipodal modifications suffer from strain, and tripod binding is ruled out. Our results suggest the viability of recursive functionalization by cross‐linking.
Identification of 1H‐indene‐(1,3,5,6)‐tetrol derivatives as potent pancreatic lipase inhibitors using molecular docking and molecular dynamics approach
Authors: Kalathiya Umesh , Padariya M. , Baginski M.
Published: August 2015

Pancreatic lipase is a potential therapeutic target to treat diet‐induced obesity in humans, as obesity‐related diseases continue to be a global problem. Despite intensive research on finding potential inhibitors, very few compounds have been introduced to clinical studies. In this work, new chemical scaffold 1H‐indene‐(1,3,5,6)‐tetrol was proposed using knowledge‐based approach, and 36 inhibitors were derived by modifying its functional groups at different positions in scaffold. To explore binding affinity and interactions of ligands with protein, CDOCKER and AutoDock programs were used for molecular docking studies. Analyzing results of rigid and flexible docking algorithms, inhibitors C_12, C_24, and C_36 were selected based on different properties and high predicted binding affinities for further analysis. These three inhibitors have different moieties placed at different functional groups in scaffold, and to characterize structural rationales for inhibitory activities of compounds, molecular dynamics simulations were performed (500 nSec). It has been shown through simulations that two structural fragments (indene and indole) in inhibitor can be treated as isosteric structures and their position at binding cleft can be replaced by each other. Taking into account these information, two lines of inhibitors can further be developed, each line based on a different core scaffold, that is, indene/indole.
Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography–mass spectrometry
Authors: Burkard Lexi , Scheuermann Alexis , Simithy Johayra , Calderón Angela I.
Published: August 2015

Plasmodium falciparum (Pf) like most other organisms, has a sophisticated antioxidant system, part of which includes glutathione reductase (GR). GR works by recycling toxic glutathione disulfide to glutathione, thereby reducing reactive oxygen species and making a form of glutathione (GSH) the parasite can use. Inhibition of this enzyme in Pf impedes parasite growth. In addition, it has been confirmed that PfGR is not identical to human GR. Thus, PfGR is an excellent target for antimalarial drug development. A functional assay utilizing liquid chromatography–mass spectrometry was developed to specifically identify and evaluate inhibitors of PfGR. Using recombinant PfGR enzyme and 1,4‐naphthoquinone (1) as a reference compound and 4‐nitrobenzothiadiazole (2) and methylene blue (3) as additional compounds, we quantified the concentration of GSH produced compared with a control to determine the inhibitory effect of these compounds. Our results coincide with that presented in literature: compounds 1–3 inhibit PfGR with IC50 values of 2.71, 8.38, and 19.23 µm, respectively. Good precision for this assay was exhibited by low values of intraday and interday coefficient of variation (3.1 and 2.4%, respectively). Thus, this assay can be used to screen for other potential inhibitors of PfGR quickly and accurately. Copyright © 2015 John Wiley & Sons, Ltd.
(Chemotaxonomic) Implications of Postharvest/Storage‐Induced Changes in Plant Volatile Profiles – the Case of Artemisia absinthium L. Essential Oil
Authors: Blagojević Polina D. , Radulović Niko S. , Skropeta Danielle
Published: August 2015

The plant volatile profile and the essential‐oil chemical composition change during the storage of plant material. The objective of this study was to develop a mathematical model able to predict, explain, and quantify these changes. Mathematical equations, derived under the assumption that the essential oil contained within plant material could be treated as an ideal solution (Raoult's law), were applied for tracking of postharvest changes in the volatile profile of Artemisia absinthium L. (the essential oils were analyzed by GC‐FID and GC/MS). Starting from a specific chemical composition of an essential‐oil sample obtained from plant material after a short drying period (typically 5–10 d), and by using the equations derived from this model, one could easily predict evaporation‐induced changes in the volatile profile of the plant material. Based on the composition of the essential‐oil sample obtained after a given storage time t, it is possible to identify those components that were involved in chemical reactions, both as reactants and possible products. The established model even allowed the recognition of pairs of transformation, i.e., ‘daughter’ products and their ‘parent’ compounds. The obtained results highlight that the essential‐oil composition is highly dependent on the storage period of any plant material and urges caution in different types of phytochemical studies, especially chemotaxonomic ones, or practical application.
Fatty‐Acid Composition of Seeds and Chemotaxonomic Evaluation of Sixteen Sapindaceae Species
Authors: Coutinho Diogenes J. Gusmão , Barbosa Mariana O. , Silva Rejane M. , da Silva Suzene I. , de Oliveira Antonio Fernando M.
Published: August 2015

Circumscriptions for the Sapindaceae family and its infrafamilial relationships have been widely discussed. Certain groups are highly morphologically similar; thus, it is difficult to identify certain taxa. DNA Analyses have also indicated complex phylogenetic relationships, and it is difficult to relate such analyses to morphological data. Given the above concerns, this study aimed to investigate the fatty‐acid profiles of the seed oils of 16 Sapindaceae species belonging to five tribes and to evaluate their potential chemotaxonomic significance. In total, eleven fatty acids were identified, and eicosenoic acid predominated in nine species. Multivariate analyses (principal component and cluster analyses) of the fatty‐acid profiles of the seed oils allowed to separate them in two major clusters. The first cluster, characterized by oils with high eicosenoic acid levels, included all species belonging to the Paullinieae tribe (Cardiospermum, Paullinia, and Serjania species). In the second main cluster, the chemical similarity of the oils was lower, and the species belonged to different tribes. Nevertheless, the tree investigated Allophylus species (Thouinieae tribe) constituted a separate subcluster. Thus, the results showed that the fatty‐acid composition of the seed oils of Sapindaceae species provide chemotaxonomic support for the separation of the Paullinieae tribe from the other tribes studied.
Five New Guaiane Sesquiterpenes from the Endophytic Fungus Xylaria sp. YM 311647 of Azadirachta indica
Authors: Huang Rong , Xie Xiao‐Song , Fang Xiao‐Wei , Ma Kai‐Xia , Wu Shao‐Hua
Published: August 2015

Five new guaiane sesquiterpenes, 1–5, were isolated from the culture broth of the endophytic fungus Xylaria sp. YM 311647, isolated from Azadirachta indica A. Juss. The structures of these compounds were elucidated on the basis of spectroscopic analyses, and their inhibitory activities against five pathogenic fungi were evaluated. All guaiane sesquiterpenes showed moderate or weak antifungal activities in a broth microdilution assay.
Kinetics of Catalytic Oxidation of Sulfite in Diluted Aqueous Solutions
Authors: Opletal Michal , Novotný Petr , Rejl František J. , Moucha Tomáš , Kordač Michal
Published: August 2015

The reaction kinetics for low concentrations of sulfite close to the stoichiometric ration of oxygen was investigated in a rapid‐mixing apparatus. Air‐ or pure oxygen‐saturated solution containing the catalyst was mixed with aqueous sulfite solution. Mixing ratios with stoichiometric excess of dissolved oxygen were tested. Reaction orders for sulfite, oxygen, and a Co(II) catalyst from literature were confirmed in the tested concentration range. The apparent kinetic constant and activation energy data are presented. The high importance of proper mixing of the two reacting solutions is reported, which was revealed during the development of the precise experimental technique providing reliable kinetic data.
Mass Transfer from Single Taylor Bubbles in Minichannels
Authors: Kastens Sven , Hosoda Shogo , Schlüter Michael , Tomiyama Akio
Published: August 2015

Mass transfer from single CO2 Taylor bubbles in vertical minichannels was measured for various channel hydraulic diameters Dh. The effects of channel geometries on the mass transfer were also investigated by using square ducts and circular pipes. Bubble rising velocities, vB, in the ducts were much faster than those in the pipes due to large liquid flow areas in the corners of the ducts. The values of mass transfer coefficients in the pipes were almost the same as those in the ducts, in spite of a large difference in vB. Sherwood numbers, ShD, using Dh as a characteristic length, are well‐correlated in terms of the Eötvös number. The proposed ShD correlation can well predict a long‐term dissolution process of a Taylor bubble.
Mechanistic Investigations of the Stereoselective Rare Earth Metal‐Mediated Ring‐Opening Polymerization of β‐Butyrolactone
Authors: Altenbuchner Peter T. , Kronast Alexander , Kissling Stefan , Vagin Sergei I. , Herdtweck Eberhardt , Pöthig Alexander , Deglmann Peter , Loos Robert , Rieger Bernhard
Published: August 2015

Poly(3‐hydroxybutyrate) (PHB) is produced by numerous bacteria as carbon and energy reserve storage material. Whereas nature only produces PHB in its strictly isotactic (R) form, homogeneous catalysis, when starting from racemic (rac) β‐butyrolactone (BL) as monomer, can in fact produce a wide variety of tacticities. The variation of the metal center and the surrounding ligand structure enable activity as well as tacticity tuning. However, no homogeneous catalyst exists to date that is easy to modify, highly active, and able to produce PHB with high isotacticities fromrac‐β‐BL. Therefore, in this work, the reaction kinetics of various 2‐methoxyethylamino‐bis(phenolate) lanthanide (Ln=Sm, Tb, Y, Lu) catalysts are examined in detail. The order in monomer and catalyst are determined to elucidate the reaction mechanism and the results are correlated with DFT calculations of the catalytic cycle. Furthermore, the enthalpies and entropies of the rate‐determining steps are determined through temperature‐dependent in situ IR measurements. Experimental and computational results converge in one specific mechanism for the ring‐opening polymerization of BL and even allow us to rationalize the preference forsyndiotacticPHB.
Stabilizing and Activating Nitrogen Catenates
Authors: Bohle D. Scott , Chua Zhijie , Singer Hobbs Maya , Perepichka Inna , Waked Alexander
Published: August 2015

The remarkably stable catenated hexa‐nitrogen chain in bis(benzotriazene‐4‐one) is structurally, theoretically, and spectroscopically characterized to illustrate the durability of the central NN bond in this hexaazo chain. The reactions of this species illustrate the potential of these nitrogen catenates for the preparation of other condensed heterocycles, such as bispyrazolones, by thermal nitrogen exclusion or by trapping the single ring‐opened Dimroth intermediates. In these latter reactions, 2‐naphtholate anion condenses with bis(benzotriazene‐4‐one) to trap and retain a zwitterionic diazonium intermediate as an isolated diazo product, whereas transition metals ring effect ring‐extrusion of dinitrogen from the Dimroth intermediate to generate chelating σ‐aryls. The catenated nitrogen species can be stabilized by incorporating strong formal sp2sp2 NN σ bonds with orthogonal orientations. Extending these stabilization and activation principles may allow these types of nitrogen catenates to be useful synthons for other polyaza species.
A Prebiotic Synthesis of Pterins
Authors: Marín‐Yaseli Margarita R. , Mompeán Cristina , Ruiz‐Bermejo Marta
Published: August 2015

The genesis of life on Earth is a hypothesis of evolutionary science that can be, at least partially, tested experimentally. The prebiotic synthesis of cofactors or coenzymes is a poorly explored issue, likely because their formation under plausible prebiotic conditions is not clear. In this sense, it has been proposed that the cofactors are “molecular fossils” of an early phase of life. In contrast, Eschenmoser and Loewenthal suggested a prebiotic hydrocyanic origin of cofactor building blocks. In the present paper, the formation of a set of pterins from cyanide polymerizations is demonstrated, showing that the main structure of some cofactors can be prebiotically formed. Indeed, it was observed that aqueous aerosols additionally increase the relative composition for pterins in the insoluble NH4CN polymers synthesized. The novel identification of pterins in NH4CN polymers, together with the previous detection of other important biomonomers, indicates that cyanide polymerizations were essential in the early state of prebiotic chemistry.
Palladiumkatalyse im industriellen Einsatz
Authors: Schlummer Björn
Published: August 2015

Palladiumkatalysierte Reaktionen sind mittlerweile fest als industrielle Produktionstechnologie etabliert. Hierbei sind die C‐C‐ aber auch die C‐N‐Kreuzkupplungsreaktionen in der homogenen Katalyse zu herausragender Bedeutung gelangt. Aufgrund der Vielfältigkeit der einsetzbaren Kupplungspartner sind neue Substanzklassen einfach zugänglich geworden, die unterschiedlichste Funktionalitäten auf verschiedensten Feldern der biologischen oder technischen Applikationen zeigen. Die Einfachheit und Robustheit dieser Synthesetechnik trägt wesentlich zur erfolgreichen technischen Implementierung bei.
Paracetamol: gefährlicher als man denkt!
Authors: Brune Kay
Published: August 2015

Vor 130 Jahren wurde durch einen Zufall die antipyretische Wirkung des Acetanilids, eines direkten Abkömmlings des Anilins entdeckt. Trotz gefährlicher Methämoglobinbildung fand Acetanilid und das daraus entwickelte Phenacetin weltweit Anwendung. Phenacetin kam nach 50 Jahren intensiven Gebrauchs in Verdacht, Nierenschäden auszulösen. Dieses Problem sollte durch die Anwendung von Paracetamol, des Hauptabbauprodukts des Phenacetins, vermieden werden. Paracetamol erwies sich allerdings als hepatotoxisch. Auch gefährliche Hautreaktionen und eine erhöhte Leukämiegefahr werden vermutet. Wissenschaftliche Ergebnisse der letzten Jahre zeigen, dass Paracetamol bei geringer analgetischer Wirksamkeit das Auftreten aller Probleme der nichtsteroidalen Analgetika (Zyklooxygenasehemmer) provozieren kann: Magen‐Darm‐Schäden, Herzinfarkte und Schlaganfälle. Zusätzlich löst es gelegentlich bereits in therapeutischer Dosierung schwere Leberschäden aus. Da es harmlosere und wirksamere Schmerzmittel gibt, sollte der Einsatz von Paracetamol überdacht werden. Modernen Sicherheitsanforderungen entspricht dieser Wirkstoff nicht. Eine Neuzulassung wäre heute unmöglich.
Experimental Design of Fenton Process for the Oxidation and Mineralization of Monocrotophos
Authors: Üstün Gökhan Ekrem , Solmaz Seval Kutlu Akal , Azak Hilal Safiye
Published: August 2015

In this study, the Fenton treatment of Monocrotophos (MCP) was evaluated in terms of oxidation and mineralization efficiency using response surface methodology (RSM). The effects of MCP, Fe2+, H2O2 concentrations and reaction time, and the interactions between these factors on (i) the oxidation efficiency of MCP and (ii) the mineralization of MCP were studied. Hence, the objective of this study was to optimize MCP oxidation and mineralization by the Fenton process (FP) using RSM. The obtained optimum conditions for MCP oxidation and mineralization using FP were 0.022:0.03:0.15 MCP/Fe2+/H2O2 and a reaction time of 65 min. MCP was mineralized easily through the Fenton reaction. The MCP oxidation efficiency was 90% and the mineralization efficiency was 66%. The initial MCP concentration was the most significant variable affecting both the oxidation and mineralization efficiency of MCP. Addition of Fe2+ had a more significant effect on the MCP oxidation compared to the MCP mineralization.
Synthesis of 2‐[18F]Fluoro‐2‐deoxyisosorbide 5‐mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET)
Authors: Santschi Nico , Wagner Stefan , Daniliuc Constantin , Hermann Sven , Schäfers Michael , Gilmour Ryan
Published: August 2015

Herein we disclose the synthesis of 2‐fluoro‐2‐deoxyisosorbide 5‐mononitrate (2F‐IS‐5MN), a fluorinated analogue of the commonly prescribed vasodilator isosorbide 5‐mononitrate (IS‐5MN). X‐ray structural data for IS‐5MN and its C2‐epimeric congener IM‐5MN are presented together with structural data for 2F‐IS‐5MN. Radioisotope labeling of 2F‐IS‐5MN has, for the first time, allowed observation of the in vivo biodistribution of this organic nitrate by means of dynamic positron emission tomography (PET) in wild‐type mice.
Remote storage management in science gateways via data bridging
Authors: Hajnal Ákos , Márton István , Farkas Zoltán , Kacsuk Péter
Published: August 2015

State‐of‐the‐art science gateways can be connected to several distributed computing infrastructures (DCIs) and are able to run jobs and workflows simultaneously in all those DCIs. Flexibility of accessing diverse data storages from these workflows and assisting end users to manage these storages are however the missing features in current gateway implementations, in which these problems often prove to be a barrier of exploiting the power of distributed computing by user communities having no or little IT competence. This paper addresses these issues by integrating a data bridging service called Data Avenue into WS‐PGRADE/gUSE portal framework. Data Avenue offers tools for the end users to easily manage their data residing on various storage resources, and also, jobs become capable of accessing different storages regardless of the particular distributed computing infrastructure where the job is currently being run. Copyright © 2014 John Wiley & Sons, Ltd.
An experimental test on time constraint and sexual conflict over parental care
Authors: Griggio Matteo
Published: August 2015

Because parental care is costly, a sexual conflict between parents over parental investment is expected to arise. Parental care behavior is an adaptive decision, involving trade‐offs between remating, and consequently desertion of the brood, and continuing parental effort. If the main advantage of desertion is remating, then this will be a time constraint, because the deserting individual will require a certain minimum period of time to breed again in the same breeding season. So, a short breeding season should force certain individuals to desert the first brood to have enough time to successfully complete their second breeding attempt. The rock sparrow, Petronia petronia, is an unusual species in which brood desertion can occur in both sexes and the breeding season is quite short so it is a good species to investigate the role of time constraint on brood desertion. For 3 years, I investigated the brood desertion modality of the rock sparrow. Then, for 2 years, I removed a group of experimental nest boxes during the autumn. Later, I re‐installed the experimental nest boxes after the start of the breeding season (2 weeks after the first egg was laid), mimicking a shortening of the breeding season for the (experimental) pairs that used experimental nest boxes. I found that in the experimental pairs, the percentage of deserting individuals was significantly higher than in the control groups, and the deserting individuals were older females. This experiment adds to our knowledge of timing of reproduction effects on individual decisions to desert by showing that a short and delayed breeding season may have different effects on males and females. To my knowledge, this is the first experimental study that demonstrates a direct link between time constraint and brood desertion.
Type I IFN‐mediated synergistic activation of mouse and human DC subsets by TLR agonists
Authors: Kreutz Martin , Bakdash Ghaith , Dolen Yusuf , Sköld Annette E. , van Hout‐Kuijer Maaike A. , de Vries I. Jolanda M. , Figdor Carl G.
Published: August 2015

Novel approaches of dendritic cell (DC) based cancer immunotherapy aim at harnessing the unique attributes of different DC subsets. Classical monocyte‐derived DC vaccines are currently being replaced by either applying primary DCs or specifically targeting antigens and adjuvants to these subsets in vivo. Appropriate DC activation in both strategies is essential for optimal effect. For this purpose TLR agonists are favorable adjuvant choices, with TLR7 triggering being essential for inducing strong Th1 responses. However, mouse CD8α+ DCs, considered to be the major cross‐presenting subset, lack TLR7 expression. Interestingly, this DC subset can respond to TLR7 ligand upon concurrent TLR3 triggering. Nevertheless, the mechanism underlying this synergy remains obscure. We now show that TLR3 ligation results in the production of IFN‐α, which rapidly induces the expression of TLR7, resulting in synergistic activation. Moreover, we demonstrate that this mechanism conversely holds for plasmacytoid DCs that respond to TLR3 ligation when TLR7 pathway is mobilized. We further demonstrate that this mechanism of sharpening DC senses is also conserved in human BDCA1+ DCs and plasmacytoid DCs. These findings have important implications for future clinical trials as it suggests that combinations of TLR ligands should be applied irrespective of initial TLR expression profiles on natural DC subsets for optimal stimulation.
What would Treg‐cell biology look like when viewed from a rationalized perspective?
Authors: Cohn Melvin
Published: August 2015

The argument that Treg cells play a role in determining the Self (S)‐Nonself (NS) discrimination (i.e. tolerance) is challenged based on two theoretical constructs, the two stage–two signal model for the S‐NS discrimination and the Tritope model of TCR function. The conclusions are then tested by reinterpreting a published probing set of data purporting to show that Treg cells regulate tolerance. It is concluded that the major role of suppression is to operate as a feedback mechanism modulating the magnitude of the effector response; it is not a determinant of the S‐NS discrimination (i.e. tolerance).
Starved human T lymphocytes keep fighting
Authors: Finlay David K.
Published: August 2015

Cellular metabolism is emerging as a key determinant of T‐lymphocyte differentiation and function. While this new paradigm has been primarily characterized in murine systems, research is now characterizing a role for different aspects of cellular metabolism in controlling human T‐lymphocyte biology. In this issue of the European Journal of Immunology, Renner et al. [Eur. J. Immunol. 2015. 45: 2504–2516] analyze the glycolytic and mitochondrial activity of activated human CD4+ and CD8+ T cells, and correlate it to T‐cell function. The authors show that although neither glucose deprivation nor mitochondrial restriction affects cytokine production, the glycolytic inhibitor 2‐deoxyglucose severely affects T‐cell function.
Advances in capillary electrophoresis for miniaturizing assays on kinase enzymes for drug discovery
Authors: Nehmé Reine , Morin Philippe
Published: August 2015

CE has become a frequently used tool for miniaturizing enzyme assays due particularly to its well‐recognized low sample consumption. CE‐based enzyme assays cover all aspects of kinetic analysis including the evaluation of enzyme activity, substrate and modulator characterization, and identification. These assays are performed to conduct high‐quality primary (hit finding) and secondary (confirmation by determining the half maximal inhibitory concentration, IC50) screening. Nowadays, the kinase family is among the most actively studied pharmaceutical targets in oncology, and in neurodegenerative and inflammation diseases. In this article, we review the fundamentals of the different approaches that may be employed for assaying kinase kinetics. Their advantages and limitations will also be discussed by covering the literature of CE‐based assays for purified kinases as well as for kinases in living cells. The last section will be devoted to perspectives by showing some applications of multiplexed and of microchip devices for high‐throughput screening kinase assays.
Recent advances in the application of capillary electromigration methods for food analysis and Foodomics
Authors: Acunha Tanize , Ibáñez Clara , García‐Cañas Virginia , Simó Carolina , Cifuentes Alejandro
Published: August 2015

This review work presents and discusses the main applications of capillary electromigration methods in food analysis and Foodomics. Papers that were published during the period February 2013–February 2015 are included following the previous review by Garcia‐Cañas et al. (Electrophoresis, 2014, 35, 147–169). Analysis by CE of a large variety of food‐related molecules with different chemical properties, including amino acids, hazardous amines, peptides, proteins, phenols, polyphenols, lipids, carbohydrates, DNAs, vitamins, toxins, contaminants, pesticides, residues, food additives, as well as small organic and inorganic compounds. This work includes recent results on food quality and safety, nutritional value, storage, bioactivity, as well as applications of CE for monitoring food processing. The use, among other CE developments, of microchips, CE‐MS, and chiral CE in food analysis and Foodomics is also discussed.
Phenolic compounds, antioxidant, and antibacterial properties of pomace extracts from four Virginia‐grown grape varieties
Authors: Xu Yixiang , Burton Sheanell , Kim Chyer , Sismour Edward
Published: August 2015

Grape pomace is a potential source of natural antioxidant and antimicrobial agents. Phenolic compounds, antioxidant, and antibacterial properties of pomace extracts from four Virginia‐grown grape varieties were investigated. White grape pomaces had higher (P < 0.05) solvent extraction yield than red varieties. Concentrations of total phenolic (TPC), total flavonoid (TFC), total anthocyanin (TAC), tannins, condensed tannins (CT), as well as antioxidant capacities (DPPH• and ABTS•+free radical scavenging) differed (P < 0.05) among four pomace extracts. ABTS•+ scavenging capacity was positively correlated with TPC, TFC, tannins, and CT (P < 0.05), whereas DPPH• capacity was positively correlated with TAC (P < 0.05). Nine flavonoid compounds were identified, of which catechin and epicatechin were the two most abundant. Antibacterial activity was observed against Listeria monocytogenes ATCC 7644 and Staphylococcus aureus ATCC 29213, but not against Escherichia coli O157:H7 ATCC 3510 and Salmonella typhimurium ATCC 14028. L. monocytogenes was more susceptible than S. aureus.
Metformin use and survival after colorectal cancer: A population‐based cohort study
Authors: Mc Menamin Úna C. , Murray Liam J. , Hughes Carmel M. , Cardwell Chris R.
Published: August 2015

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time‐related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer‐specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer‐specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time‐dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post‐diagnostic exposure to metformin and colorectal cancer‐specific mortality. Overall, there was no evidence of an association between metformin use and cancer‐specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer‐specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti‐diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all‐cause mortality. This population‐based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.
The complex relationship between human papillomavirus and cervical adenocarcinoma
Authors: Molijn Anco , Jenkins David , Chen Wen , Zhang Xun , Pirog Edyta , Enqi Wu , Liu Bin , Schmidt Johannes , Cui Jiangfeng , Qiao Youlin , Quint Wim ,   on behalf of Chinese HPV Typing Group
Published: August 2015

Human Papillomavirus (HPV) is reported in 60–100% of cervical adenocarcinoma (CADC) globally. We investigated this relationship in a hospital‐based survey in China. 718 CADC samples from nine Chinese regions were analysed. Expert pathologists reviewed cases with p16 and progesterone receptor immunostaining. Cases were tested for HPV using whole‐tissue sections (WTS) and laser‐capture microdissection. All cases were HPV‐tested by L1 based broad‐spectrum SPF10‐DEIA‐LiPA25 PCR. Negative cases were tested for DNA adequacy and with E6 oncogene, type‐specific HPV PCRs. Using WTS‐PCR CADC showed overall 75% HPV‐positivity (33–100% for different histological types). LCM‐PCR showed that none of minimal deviation or serous CADC, and <10% of all clear cell and endometrioid CADC were HPV‐positive in tumour cells. Usual and adenosquamous CADC showed a single HPV genotype in 60 and 78% cases. In some cases, HPV was found in adjacent cervix but not in tumour. HPV 16, 18 and 45 accounted for 90% of HPV in tumour cells. Patients with HPV‐positive tumours were on average 6 years younger and presented at a lower clinicopathological stage as compared to patients with HPV‐negative cancers. CADC is diverse pathologically and in HPV status. Special histopathological tumor subtypes may develop through different cellular and molecular pathways. Between 20 and 40% usual and adenosquamous types, in particular these diagnosed in older women and at advanced FIGO stages, are not driven by oncogenic HPV. In these cases HPV may not be involved in carcinogenisis or maybe lost during tumour progression.
Heat shock proteins in hepatocellular carcinoma: Molecular mechanism and therapeutic potential
Authors: Wang Cun , Zhang Yurong , Guo Kun , Wang Ning , Jin Haojie , Liu Yinkun , Qin Wenxin
Published: August 2015

Heat shock proteins (HSPs) are highly conserved proteins, which are expressed at low levels under normal conditions, but significantly induced in response to cellular stresses. As molecular chaperones, HSPs play crucial roles in protein homeostasis, apoptosis, invasion and cellular signaling transduction. The induction of HSPs is an important part of heat shock response, which could help cancer cells to adapt to stress conditions. Because of the constant stress condition in tumor microenvironment, HSPs overexpression is widely reported in many human cancers. In light of the significance of HSPs for cancer cells to survive and obtain invasive phenotype under stress condition, HSPs are often associated with poor prognosis and treatment resistance in many types of human cancers. It has been described that upregulation of HSPs may serve as diagnostic and prognostic markers in hepatocellular carcinoma (HCC). Targeting HSPs with specific inhibitor alone or in combination with chemotherapy regimens holds promise for the improvement of outcomes for HCC patients. In this review, we summarize the expression profiles, functions and molecular mechanisms of HSPs (HSP27, HSP70 and HSP90) as well as a HSP‐like protein (clusterin) in HCC. In addition, we address progression and challenges in targeting these HSPs as novel therapeutic strategies in HCC.
High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan
Authors: Amayiri Nisreen , Tabori Uri , Campbell Brittany , Bakry Doua , Aronson Melyssa , Durno Carol , Rakopoulos Patricia , Malkin David , Qaddoumi Ibrahim , Musharbash Awni , Swaidan Maisa , Bouffet Eric , Hawkins Cynthia , Al‐Hussaini Maysa ,   On behalf of BMMRD consortium
Published: August 2015

Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome affecting primarily individuals from consanguinous families resulting in multiple childhood cancers including high grade gliomas (HGG). This is the first study to assess the prevalence of bMMRD among patients with HGG in countries where consanguinity is high. We collected molecular and clinical information on all children diagnosed with HGG and supratentorial primitive neuroectodermal tumors (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison was made to a similar cohort from Toronto. Clinical data regarding presence of café au lait macules(CAL), family history of cancer, consanguinity, pathology and treatment were collected. Tumors were centrally reviewed and tested for MMRD by immunohistochemistry of the corresponding proteins. Forty‐two patients fulfilled the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of whom79% also lost MMR staining in the corresponding normal cells suggestive of bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (p = 0.0003).The frequency of MMRD was significantly lower in Toronto cohort (23%, p = 0.03). Both evidence of CAL and consanguinity correlated with bMMRD (p = 0.005 and 0.05,respectively) but family history of cancer didn't. HGG with all three bMMRD risk factors had evidence of MMRD and all children affected by multiple bMMRD related cancers had identical gene loss by immunohistochemical staining. In Jordan, the frequency of clinical and immunohistochemical alterations suggestive of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate counseling and cancer screening to improve survival of these patients.