bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge S
copalina ruetzleri
Authors: Biegelmeyer Renata , Schröder Rafael , Rambo Douglas F , Dresch Roger R , Stout E Paige , Carraro João L F , Mothes Beatriz , Moreira José C F , Molinski Tadeusz F , da Frota Junior Mário L C , Henriques Amélia T
Published: January 2015

Objectives

Marine sponges are among the most promising sources of chemically diversified fatty acids (FAs). In addition, several studies have shown the effect of polyunsaturated FAs on cancer therapy. This research carried out a biological and chemical evaluation of the sponge Scopalina ruetzleri collected on the South Brazilian coastline.

Methods

Bioassay-guided fractionation of S. ruetzleri was performed in human glioma (U87) and neuroblastoma (SH-SY5Y) cell lines, and the in-vitro effects on free radicals were evaluated.

Key findings

The ethyl acetate fraction of S. ruetzleri showed promising cytotoxic effects in cancer cell lines, with IC50 < 20 μg/ml. Fingerprint 1H Nuclear Magnetic Resonance (NMR) analysis showed that this fraction is mainly constituted of FAs. Through FA methyl ester analysis, it was possible to identify 32 FAs. In addition, some minor unusual FAs for the marine biosphere were identified. The results of conjugated dienes method showed that FAs fraction, at concentrations above 50 μg/ml, has a pro-oxidant effect, indicating that lipid peroxidation may be partially responsible for the mechanism of cytotoxicity on cancer cells.

Conclusion

This work also contributes to studies that focus on the application of FAs on cancer therapy as a new adjuvant to radio or chemotherapy, or as a chemotherapeutic agent.
The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm – volume 2
Authors: Hatzakis A. , Chulanov V. , Gadano A. C. , Bergin C. , Ben‐Ari Z. , Mossong J. , Schréter I. , Baatarkhuu O. , Acharya S. , Aho I. , Anand A. C. , Andersson M. I. , Arendt V. , Arkkila P. , Barclay K. , Bessone F. , Blach S. , Blokhina N. , Brunton C. R. , Choudhuri G. , Cisneros L. , Croes E. A. , Dahgwahdorj Y. A. , Dalgard O. , Daruich J. R. , Dashdorj N. R. , Davaadorj D. , de Knegt R. J. , de Vree M. , Estes C. , Flisiak R. , Gane E. , Gower E. , Halota W. , Henderson C. , Hoffmann P. , Hornell J. , Houlihan D. , Hrusovsky S. , Jarčuška P. , Kershenobich D. , Kostrzewska K. , Kristian P. , Leshno M. , Lurie Y. , Mahomed A. , Mamonova N. , Mendez‐Sanchez N. , Norris S. , Nurmukhametova E. , Nymadawa P. , Oltman M. , Oyunbileg J. , Oyunsuren Ts. , Papatheodoridis G. , Pimenov N. , Prabdial‐Sing N. , Prins M. , Radke S. , Rakhmanova A. , Razavi‐Shearer K. , Reesink H. W. , Ridruejo E. , Safadi R. , Sagalova O. , Sanchez Avila J. F. , Sanduijav R. , Saraswat V. , Seguin‐Devaux C. , Shah S. R. , Shestakova I. , Shevaldin A. , Shibolet O. , Silva M. O. , Sokolov S. , Sonderup M. , Souliotis K. , Spearman C. W. , Staub T. , Stedman C. , Strebkova E. A. , Struck D. , Sypsa V. , Tomasiewicz K. , Undram L. , van der Meer A. J. , van Santen D. , Veldhuijzen I. , Villamil F. G. , Willemse S. , Zuckerman E. , Zuure F. R. , Puri P. , Razavi H.
Published: January 2015

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.
Strategies to manage hepatitis C virus (HCV) infection disease burden – volume 2
Authors: Gane E. , Kershenobich D. , Seguin‐Devaux C. , Kristian P. , Aho I. , Dalgard O. , Shestakova I. , Nymadawa P. , Blach S. , Acharya S. , Anand A. C. , Andersson M. I. , Arendt V. , Arkkila P. , Baatarkhuu O. , Barclay K. , Ben‐Ari Z. , Bergin C. , Bessone F. , Blokhina N. , Brunton C. R. , Choudhuri G. , Chulanov V. , Cisneros L. , Croes E. A. , Dahgwahdorj Y. A. , Daruich J. R. , Dashdorj N. R. , Davaadorj D. , de Knegt R. J. , de Vree M. , Gadano A. C. , Gower E. , Halota W. , Hatzakis A. , Henderson C. , Hoffmann P. , Hornell J. , Houlihan D. , Hrusovsky S. , Jarčuška P. , Kostrzewska K. , Leshno M. , Lurie Y. , Mahomed A. , Mamonova N. , Mendez‐Sanchez N. , Mossong J. , Norris S. , Nurmukhametova E. , Oltman M. , Oyunbileg J. , Oyunsuren Ts. , Papatheodoridis G. , Pimenov N. , Prins M. , Puri P. , Radke S. , Rakhmanova A. , Razavi H. , Razavi‐Shearer K. , Reesink H. W. , Ridruejo E. , Safadi R. , Sagalova O. , Sanchez Avila J. F. , Sanduijav R. , Saraswat V. , Schréter I. , Shah S. R. , Shevaldin A. , Shibolet O. , Silva M. O. , Sokolov S. , Sonderup M. , Souliotis K. , Spearman C. W. , Staub T. , Stedman C. , Strebkova E. A. , Struck D. , Sypsa V. , Tomasiewicz K. , Undram L. , van der Meer A. J. , van Santen D. , Veldhuijzen I. , Villamil F. G. , Willemse S. , Zuckerman E. , Zuure F. R. , Prabdial‐Sing N. , Flisiak R. , Estes C.
Published: January 2015

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV‐related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.
Highly siderophile element (HSE) abundances in the mantle of Mars are due to core formation at high pressure and temperature
Authors: Righter K. , Danielson L. R. , Pando K. M. , Williams J. , Humayun M. , Hervig R. L. , Sharp T. G.
Published: January 2015

Highly siderophile elements (HSEs) can be used to understand accretion and core formation in differentiated bodies, due to their strong affinity for FeNi metal and sulfides. Coupling experimental studies of metal–silicate partitioning with analyses of HSE contents of Martian meteorites can thus offer important constraints on the early history of Mars. Here, we report new metal–silicate partitioning data for the PGEs and Au and Re across a wide range of pressure and temperature space, with three series designed to complement existing experimental data sets for HSE. The first series examines temperature effects for D(HSE) in two metallic liquid compositions—C‐bearing and C‐free. The second series examines temperature effects for D(Re) in FeO‐bearing silicate melts and FeNi‐rich alloys. The third series presents the first systematic study of high pressure and temperature effects for D(Au). We then combine our data with previously published partitioning data to derive predictive expressions for metal–silicate partitioning of the HSE, which are subsequently used to calculate HSE concentrations of the Martian mantle during continuous accretion of Mars. Our results show that at midmantle depths in an early magma ocean (equivalent to approximately 14 GPa, 2100 °C), the HSE contents of the silicate fraction are similar to those observed in the Martian meteorite suite. This is in concert with previous studies on moderately siderophile elements. We then consider model calculations that examine the role of melting, fractional crystallization, and sulfide saturation/undersaturation in establishing the range of HSE contents in Martian meteorites derived from melting of the postcore formation mantle. The core formation modeling indicates that the HSE contents can be established by metal–silicate equilibrium early in the history of Mars, thus obviating the need for a late veneer for HSE, and by extension volatile siderophile elements, or volatiles in general.
A Comparison of Sequential and Information‐based Methods for Determining the Co‐integration Rank in Heteroskedastic VAR Models
Authors: Cavaliere Giuseppe , Angelis Luca De , Rahbek Anders , Robert Taylor A. M.
Published: January 2015

In this article, we investigate the behaviour of a number of methods for estimating the co‐integration rank in VAR systems characterized by heteroskedastic innovation processes. In particular, we compare the efficacy of the most widely used information criteria, such as Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) , with the commonly used sequential approach of Johansen [Likelihood‐based Inference in Cointegrated Vector Autoregressive Models(1996)] based around the use of either asymptotic or wild bootstrap‐based likelihood ratio type tests. Complementing recent work done for the latter in Cavaliere, Rahbek and Taylor [Econometric Reviews(2014) forthcoming], we establish the asymptotic properties of the procedures based on information criteria in the presence of heteroskedasticity (conditional or unconditional) of a quite general and unknown form. The relative finite‐sample properties of the different methods are investigated by means of a Monte Carlo simulation study. For the simulation DGPs considered in the analysis, we find that the BIC‐based procedure and the bootstrap sequential test procedure deliver the best overall performance in terms of their frequency of selecting the correct co‐integration rank across different values of the co‐integration rank, sample size, stationary dynamics and models of heteroskedasticity. Of these, the wild bootstrap procedure is perhaps the more reliable overall as it avoids a significant tendency seen in the BIC‐based method to over‐estimate the co‐integration rank in relatively small sample sizes.
On the Practice of Lagging Variables to Avoid Simultaneity
Authors: Reed William Robert
Published: January 2015

A common practice in applied economics research consists of replacing a suspected simultaneously determined explanatory variable with its lagged value. This note demonstrates that this practice does not enable one to avoid simultaneity bias. The associated estimates are still inconsistent, and hypothesis testing is invalid. An alternative is to use lagged values of the endogenous variable in instrumental variable estimation. However, this is only an effective estimation strategy if the lagged values do not themselves belong in the respective estimating equation, and if they are sufficiently correlated with the simultaneously determined explanatory variable.
Interphotoreceptor Retinoid‐Binding Protein Protects Retinoids from Photodegradation
Authors: Gonzalez‐Fernandez Federico , Betts‐Obregon Brandi , Yust Brian , Mimun Joshua , Sung Dongjin , Sardar Dhiraj , Tsin Andrew T.
Published: January 2015

Retinol degrades rapidly in light into a variety of photoproducts. It is remarkable that visual cycle retinoids can evade photodegradation as they are exchanged between the photoreceptors, retinal pigment epithelium and Müller glia. Within the interphotoreceptor matrix, all‐trans retinol, 11‐cis retinol and retinal are bound by interphotoreceptor retinoid‐binding protein (IRBP). Apart from its role in retinoid trafficking and targeting, could IRBP have a photoprotective function? HPLC was used to evaluate the ability of IRBP to protect all‐trans and 11‐cis retinols from photodegradation when exposed to incandescent light (0 to 8842 μW cm−2); time periods of 0–60 min, and bIRBP: retinol molar ratios of 1:1 to 1:5. bIRBP afforded a significant prevention of both all‐trans and 11‐cis retinol to rapid photodegradation. The effect was significant over the entire light intensity range tested, and extended to the bIRBP: retinol ratio 1:5. In view of the continual exposure of the retina to light, and the high oxidative stress in the outer retina, our results suggest IRBP may have an important protective role in the visual cycle by reducing photodegradation of all‐trans and 11‐cis retinols. This role of IRBP is particularly relevant in the high flux conditions of the cone visual cycle.
Promoting weight loss in asthma
Authors: Dixon Anne E. , Gerald Lynn B.
Published: January 2015

See article, page 243
A Story of Post‐Fordist Exploitation: Financialization and Small‐Scale Maize Farmers in Turkey
Authors: Borlu Yetkin
Published: January 2015

After the implementation of economic restructuring policies in Turkish agriculture, farming communities experienced significant changes in the patterns of agricultural production over the last decade. The dramatic shift from labor‐intensive field crops to maize farming represents such a change, particularly for small‐scale farmers, since high‐yield maize farming is driven by private agrifood corporate demand. In this article, I explore how this shift influences the relations of production in agriculture through a commodity‐system analysis of the maize sector in Turkey. Through the qualitative analysis of the semistructured in‐depth interviews and secondary data, I find that small‐scale farmers are able to participate in maize farming, even as their dependence on production credits to participate in industrial maize farming crucially reduces their bargaining power with private industry. I argue that the traditional Marxist approach, accumulation by dispossession, is not sufficient to explain the participation of small‐scale farmers. Instead, I propose a new concept, entrepreneurial exploitation, to describe the participation of small‐scale investors in the post‐Fordist regime. Thereby, I point to the important role of expansion of credit markets as a consequence of financialization.
The Flavone Eupatilin Inhibits Eotaxin Expression in an NF‐κB‐Dependent and STAT6‐Independent Manner
Authors: Jeon J. I. , Ko S. H. , Kim Y.‐J. , Choi S. M. , Kang K. K. , Kim H. , Yoon H. J. , Kim J. M.
Published: January 2015

The CC chemokine eotaxin contributes to epithelium‐induced inflammation in airway diseases such as asthma. Eupatilin (5,7‐dihydroxy‐3′,4′,6′‐trimethoxyflavone), a bioactive component of Artemisia asiatica Nakai (Asteraceae), is reported to inhibit the adhesion of eosinophils to bronchial epithelial cells. However, little is known about the molecular mechanism of eupatilin‐induced attenuation of bronchial epithelium‐induced inflammation. In this study, we investigated the effect of eupatilin on expression of eotaxin‐1 (CCL11), a potent chemoattractant for eosinophils. Eupatilin significantly inhibited eotaxin expression in bronchial epithelial cells stimulated with TNF‐α, while NF‐κB and IκBα kinase (IKK) activities declined concurrently. Eupatilin also inhibited mitogen‐activated protein kinase (MAPK) activity; however, all of these anti‐inflammatory activities were reversed by MAPK overexpression. In contrast, eupatilin did not affect the signal transducer and activator of transcription 6 (STAT6) signalling in bronchial epithelial cells stimulated with IL‐4. Furthermore, eupatilin significantly attenuated TNF‐α‐induced eosinophil migration. These results suggest that the eupatilin inhibits the signalling of MAPK, IKK, NF‐κB and eotaxin‐1 in bronchial epithelial cells, leading to inhibition of eosinophil migration.
Contribution of IL‐12A and IL‐12B Polymorphisms to Chlamydia trachomatis‐Specific Cell‐Mediated Immune Responses
Authors: Öhman H. , Natividad A. , Bailey R. , Ragoussis J. , Johnson L.‐L. , Tiitinen A. , Halttunen M. , Paavonen J. , Surcel H.‐M.
Published: January 2015

Inherited variance in the IL‐12B gene is associated with susceptibility to Chlamydia trachomatis‐induced tubal factor infertility and disease severity. In this study, our aim was to discover how polymorphisms in IL‐12‐coding genes influence C. trachomatis‐induced immune responses and IL‐12 production. The study population consisted of 240 women. IL‐12A and IL‐12B single nucleotide polymorphisms (SNPs) were determined from isolated DNA using the Sequenom system with matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry. We studied lymphocyte proliferative (LP) responses to C. trachomatis strains E and F elementary bodies (EBs) and recombinant chlamydial heat‐shock protein 60 (CHSP60) antigen. IL‐12p40 and IL‐12p70 levels were measured using the BD Flex Set method. We found a statistically significant association between the C. trachomatis EB antigen‐specific LP response and the rs2853694 SNP (P = 0.02). Our study demonstrates that the IL‐12 cytokine family is involved in C. trachomatis‐specific immune responses. Moreover, C. trachomatis‐induced IL‐12 production and the IL‐12B rs2853694 SNP partially explain individual variation in the C. trachomatis LP response.
Cry1Ab Protein from Bacillus thuringiensis and MON810 cry1Ab‐transgenic Maize Exerts No Adjuvant Effect After Airway Exposure
Authors: Andreassen M. , Bøhn T. , Wikmark O.‐G. , Van den Berg J. , Løvik M. , Traavik T. , Nygaard U. C.
Published: January 2015

The genetically modified (GM) maize event MON810 has been inserted with a processed version of the transgene, cry1Ab, derived from the soil bacterium Bacillus thuringiensis (Bt) to express proteins with insecticidal properties. Such proteins may introduce new allergens and also act as adjuvants that promote allergic responses. While focus has been on safe consumption and hence the oral exposure to GM food and feed, little is known regarding inhalation of pollen and desiccated airborne plant material from GM crops. The aim of this study was to investigate whether plant material from the Cry1Ab‐expressing maize variety MON810, or trypsin‐activated Cry1Ab (trypCry1Ab) protein produced in recombinant bacteria, may act as adjuvants against the allergen ovalbumin (OVA) in a mouse model of airway allergy. A clear proallergic adjuvant effect of the mucosal adjuvant cholera toxin (CT) was demonstrated, determined as increased specific IgE, eosinophils and Th2 cytokines in MLN cell supernates, while no elevation in OVA‐specific antibodies or cytokine release from MLN cells after stimulation with OVA were observed in mice receiving Cry1Ab‐containing plant materials or the trypCry1Ab protein. Our data suggest that Cry1Ab proteins had no detectable systemic adjuvant effect in mice after airway exposure. Further experiments with purified plant proteins, as well as long‐term exposures needs be conducted to further evaluate exposures experienced in real‐life situations.
Phased‐array of microcoils allows MR microscopy of ex vivo human skin samples at 9.4 T
Authors: Göbel K. , Gruschke O. G. , Leupold J. , Kern J. S. , Has C. , Bruckner–Tuderman L. , Hennig J. , von Elverfeldt D. , Baxan N. , Korvink J. G.
Published: January 2015

Purpose

The aim of this study was to demonstrate the feasibility of a custom‐made phased‐array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology.

Materials and methods

A dedicated 7‐channel microcoil‐based MR detector arranged in a phased‐array geometry was developed to combine the advantages of both a large field of view and a high signal‐to‐noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo.

Results

In this study, the feasibility of using this type of microdetector, combined with specially manufactured sample holders, to achieve high‐resolution MR images of fresh and formalin‐fixed, normal and hidradenitis suppurativa diseased skin was successfully demonstrated. The setup presented in this work allows reliable acquisitions of high‐resolution images with in‐plane resolution up to 25 × 25 μm², and 100 μm in the orthogonal direction, thereby allowing the differentiation of typical layers of the skin, sebaceous glands and hair follicle.

Conclusion

This study demonstrates that MR microscopy on skin biopsies can be applied at low cost on a standard animal MR imaging system. The successful imaging of different skin structures ex vivo is a prerequisite for non‐invasive, in vivo application of skin MR microscopy for accurate complementary disease diagnosis in dermatology.
Long‐proboscid brachyceran flies in Cretaceous amber (Diptera: Stratiomyomorpha: Zhangsolvidae)
Authors: ARILLO ANTONIO , PEÑALVER ENRIQUE , PÉREZ‐DE LA FUENTE RICARDO , DELCLÒS XAVIER , CRISCIONE JULIA , BARDEN PHILLIP M. , RICCIO MARK L. , GRIMALDI DAVID A.
Published: January 2015

The monophyletic family Zhangsolvidae comprises stout‐bodied brachyceran flies with a long proboscis and occurring only in the Cretaceous, originally known in shale from the Early Cretaceous Laiyang Formation (Fm.) in China (Zhangsolva Nagatomi & Yang), subsequently from limestones of the Early Cretaceous Crato Fm. of Brazil. Cratomyoides Wilkommen is synonymized with Cratomyia Mazzarolo & Amorim, both from the Crato Fm.; Cratomyiidae is synonymized with Zhangsolvidae. Two genera and three species of Zhangsolvidae are described: Buccinatormyia magnifica Arillo, Peñalver & Pérez‐de la Fuente, gen. et sp.n. and B. soplaensis Arillo, Peñalver & Pérez‐de la Fuente, sp.n., in Albian amber from Las Peñosas Fm. in Spain; and Linguatormyia teletacta Grimaldi, gen. et sp.n., in Upper Albian–Lower Cenomanian amber from Hukawng Valley in Myanmar. Buccinatormyia soplaensis and Linguatormyia teletacta are unique among all Brachycera, extant or extinct, by their remarkably long, flagellate antennae, about 1.6× the body length in the latter species. A phylogenetic analysis of 52 morphological characters for 35 taxa is presented, 11 taxa being Cretaceous species, which supports placement of the family within Stratiomyomorpha, although not to any particular family within the infraorder.

This published work has been registered in Zoobank, http://zoobank.org/urn:lsid:zoobank.org:pub:F32CF887‐7C37‐45D5‐BD6B‐135FE9B729A7.
Host‐associated genetic divergence and taxonomy in theRhinusa pilosaGyllenhal species complex: an integrative approach
Authors: TOŠEVSKI IVO , CALDARA ROBERTO , JOVIĆ JELENA , HERNÁNDEZ‐VERA GERARDO , BAVIERA COSIMO , GASSMANN ANDRE , EMERSON BRENT C.
Published: January 2015

A combined taxonomic, morphological, molecular and biological study revealed that stem‐galling weevils from the genusRhinusaassociated with toadflaxes from the genusLinaria(Plantaginaceae) are composed of three different species:Rhinusa pilosa,Rhinusa brondeliiandRhinusa rarasp.n.The authentic field host plants are respectively,Linaria vulgaris,Linaria purpureaandLinaria genistifolia/ Linaria dalmatica. These weevil species can be distinguished from each other by a few subtle morphological characteristics, mainly in the shape of the rostrum and of the integument. An analysis of the mitochondrial [cytochrome oxidase subunit II gene (COII) and16Sribosomal RNA gene (16S)] and nuclear (elongation factor‐1α,EF‐1α) sequence data revealed high genetic divergence among these species. Uncorrected pairwise distances on mtCOIIgene were 14.3% betweenR. pilosaandR. brondelii, 15.7% betweenR. pilosaandR. rara, whileR. brondeliiandR. rarawere approximately 11% divergent from each other. Divergences obtained on16Sand nuclearEF‐1αgenes were congruent. However, substantial intraspecific mitochondrial divergence was recorded for all studied populations ofR. pilosas.s. showing two mtDNAlineages, with estimatedCOIIand16Sdivergences of 4% and 1.6%, respectively. Nuclear pseudogenes (Numts) andWolbachiainfluence, although recorded within both lineages, were excluded as possible causatives of the mtDNAdivergence, whileEF‐1αindicated absence of lineage sorting. Species from theR. pilosacomplex are estimated to have diverged from each other approximately 7.2 million years ago (mya; lateMiocene), whileR. brondeliiandR. raradiverged from each other about 4.7 mya (earlyPliocene).

This published work has been registered in ZooBank,http://zoobank.org/urn:lsid:zoobank.org:pub:EEDD6248‐01DB‐4B4A‐B79D‐C5606393E3AA.
An investigation into the relationship between age and physiological function in highly active older adults
Authors: Pollock Ross D. , Carter Scott , Velloso Cristiana P. , Duggal Niharika A. , Lord Janet M. , Lazarus Norman R. , Harridge Stephen D. R.
Published: January 2015

Key Points

The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual.

This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill‐defined and low levels of physical activity.

This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55–79 years in whom the effects of lifestyle factors would be ameliorated.

Significant associations between age and function were observed for many functions. was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual.

The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity.

Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross‐sectional nature. These include inter‐subject genetic variation, as well as inter‐generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well‐being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross‐sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies.
Single-channel blind separation using L1-sparse complex non-negative matrix factorization for acoustic signals
Authors: Parathai P. , Woo W. L. , Dlay S. S. , Gao Bin
Published: January 2015

An innovative method of single-channel blind source separation is proposed. The proposed method is a complex-valued non-negative matrix factorization with probabilistically optimal L1-norm sparsity. This preserves the phase information of the source signals and enforces the inherent structures of the temporal codes to be optimally sparse, thus resulting in more meaningful parts factorization. An efficient algorithm with closed-form expression to compute the parameters of the model including the sparsity has been developed. Real-time acoustic mixtures recorded from a single-channel are used to verify the effectiveness of the proposed method.
Sarcopenia Defined by Combining Height- and Weight-Adjusted Skeletal Muscle Indices is Closely Associated With Poor Physical Performance
Authors: Meng Nai-Hsin , Li Chia-Ing , Liu Chiu-Shong , Lin Wen-Yuan , Lin Chih-Hsueh , Chang Chin-Kai , Li Tsai-Chung , Lin Cheng-Chieh
Published: January 2015

Objectives:

To compare muscle strength and physical performance among subjects with and without sarcopenia of different definitions.

Design:

A population-based cross-sectional study.

Participants:

857 community residents aged 65 years or older.

Methods:

Sarcopenia was defined according to the European Working Group of Sarcopenia in Older People consensus criteria. Dual-energy X-ray absorptiometry measured lean soft tissue mass. Sarcopenic participants with low height-adjusted or weight-adjusted skeletal muscle index (SMI) were classified as having h-sarcopenia or w-sarcopenia, respectively. Combined sarcopenia (c-sarcopenia) was defined as having either h- or w-sarcopenia. The participants underwent six physical performance tests: walking speed, timed up-and-go, six-minute walk, single-leg stance, timed chair stands, and flexibility test. The strength of five muscle groups was measured.

Results:

Participants with h-sarcopenia had lower weight, body mass index (BMI), fat mass, and absolute muscle strength (p ≤ .001); those with w-sarcopenia had higher weight, BMI, fat mass (p < .001), and low relative muscle strength (p ≤ .003). Participants with c-sarcopenia had poorer performance in all physical performance tests, whereas h-sarcopenia and w-sarcopenia were associated with poor performance in four tests.

Conclusion:

Subjects with h- and w-sarcopenia differ significantly in terms of obesity indicators. Combining height- and weight-adjusted SMIs can be a feasible method to define sarcopenia.
Exercise for Mild Balance Dysfunction: Research into Practice
Authors: Williams Susan , Meyer Claudia , Batchelor Frances , Hill Keith
Published: January 2015

The objective of this study was to determine whether improved balance outcomes achieved in a randomized controlled trial (RCT) using balance screening to identify mild balance dysfunction and home exercises could be translated into community settings. Community-dwelling people aged over 65 who expressed concerns about their balance, had less than two falls in the preceding 12 months, and who had mild balance impairment on screening were given an individualized home-based balance and strengthening exercise program with intermittent home-visit support by a physiotherapist. Of 71 participants assessed (mean age 77.3 years, 76% female), 58 (82%) completed the six-month intervention. Twenty six percent of participants regained balance performance within normal limits—similar to those achieved in the previous RCT. Successful results from a previous RCT were able to be translated into community settings, with a similar magnitude of effect on balance and mobility.
Extended-Duration Dosing and Distribution of Dalbavancin into Bone and Articular Tissue
Authors: Dunne Michael W. , Puttagunta Sailaja , Sprenger Craig R. , Rubino Chris , Van Wart Scott , Baldassarre James
Published: January 2015

Dalbavancin is an intravenous lipoglycopeptide with activity against Gram-positive pathogens and an MIC
90
for
Staphylococcus aureus
of 0.06 μg/ml. With a terminal half-life of >14 days, dosing regimens with infrequent parenteral administration become available to treat infectious diseases such as osteomyelitis and endocarditis that otherwise require daily dosing for many weeks. In order to support a rationale for these novel regimens, the pharmacokinetics over an extended dosing interval and the distribution of dalbavancin into bone and articular tissue were studied in two phase I trials and pharmacokinetic modeling was performed. Intravenous administration of 1,000 mg of dalbavancin on day 1 followed by 500 mg weekly for seven additional weeks was well tolerated and did not demonstrate evidence of drug accumulation. In a separate study, dalbavancin concentrations in cortical bone 12 h after infusion of a single 1,000-mg intravenous infusion were 6.3 μg/g and 2 weeks later were 4.1 μg/g. A two-dose, once-weekly regimen that would provide tissue exposure over the dalbavancin MIC for
Staphylococcus aureus
for 8 weeks, maximizing the initial exposure to treatment while minimizing the frequency of intravenous therapy, is proposed.
A Phase 2, Randomized, Double-Blind, Multicenter Trial To Evaluate the Safety and Efficacy of Three Dosing Regimens of Isavuconazole Compared with Fluconazole in Patients with Uncomplicated Esophageal Candidiasis
Authors: Viljoen J. , Azie N. , Schmitt-Hoffmann A.-H. , Ghannoum M.
Published: January 2015

Esophageal candidiasis is a frequent cause of morbidity in immunocompromised patients. Isavuconazole is a novel, broad-spectrum antifungal developed for the treatment of opportunistic fungal infections. This phase 2 trial compared the efficacy and safety of three oral dosing regimens of isavuconazole with an oral fluconazole regimen in the primary treatment of uncomplicated esophageal candidiasis. The isavuconazole regimens were as follows: 200 mg on day 1 and then 50 mg once daily (arm A), 400 mg on day 1 and then 400 mg once-weekly (arm B), and 400 mg on day 1 and then 100 mg once daily (arm C). Patients in arm D received fluconazole at 200 mg on day 1 and then 100 mg once daily. The minimum treatment duration was 14 days. The primary endpoint was the rate of endoscopically confirmed clinical response at end of therapy. Safety and tolerability were also assessed. Efficacy was evaluated in 153 of 160 enrolled patients. Overall, 146 (95.4%) achieved endoscopically confirmed clinical success. Each of the isavuconazole regimens was shown to be not inferior to fluconazole, i.e., arm A versus D, −0.5% (95% confidence interval [CI] −10.0 to 9.4), arm B versus D, 3.5% (95% CI, −5.6 to 12.7), and arm C versus D, −0.2% (95% CI, −9.8 to 9.4). The frequency of adverse events was similar in arm A (
n
= 22; 55%), arm B (
n
= 18; 45%), and arm D (
n
= 22; 58%), but higher in arm C (
n
= 29; 71%). In summary, efficacy and safety of once-daily and once-weekly isavuconazole were comparable with once-daily fluconazole in the primary treatment of uncomplicated esophageal candidiasis.
Molecular Mechanisms of Sulbactam Antibacterial Activity and Resistance Determinants in Acinetobacter baumannii
Authors: Penwell William F. , Shapiro Adam B. , Giacobbe Robert A. , Gu Rong-Fang , Gao Ning , Thresher Jason , McLaughlin Robert E. , Huband Michael D. , DeJonge Boudewijn L. M. , Ehmann David E. , Miller Alita A.
Published: January 2015

Sulbactam is a class A β-lactamase inhibitor with intrinsic whole-cell activity against certain bacterial species, including
Acinetobacter baumannii
. The clinical use of sulbactam for
A. baumannii
infections is of interest due to increasing multidrug resistance in this pathogen. However, the molecular drivers of its antibacterial activity and resistance determinants have yet to be precisely defined. Here we show that the antibacterial activities of sulbactam vary widely across contemporary
A. baumannii
clinical isolates and are mediated through inhibition of the penicillin-binding proteins (PBPs) PBP1 and PBP3, with very low frequency of resistance; the rare
pbp3
mutants with high levels of resistance to sulbactam are attenuated in fitness. These results support further investigation of the potential clinical utility of sulbactam.
The Sensor Histidine Kinase RgfC Affects Group B Streptococcal Virulence Factor Expression Independent of Its Response Regulator RgfA
Authors: Gendrin Claire , Lembo Annalisa , Whidbey Christopher , Burnside Kellie , Berry Jessica , Ngo Lisa , Banerjee Anirban , Xue Liang , Arrington Justine , Doran Kelly S. , Tao W. Andy , Rajagopal Lakshmi
Published: January 2015

Group B streptococci (GBS;Streptococcus agalactiae) are beta-hemolytic, Gram-positive bacteria that are common asymptomatic colonizers of healthy adults. However, these opportunistic bacteria also cause invasive infections in human newborns and in certain adult populations. To adapt to the various environments encountered during its disease cycle, GBS encodes a number of two-component signaling systems. Previous studies have indicated that the TCS comprising the sensor histidine kinase RgfC and the response regulator RgfA mediate GBS binding to extracellular matrix components, such as fibrinogen. However, in certain GBS clinical isolates, a point mutation inrgfAresults in premature truncation of the response regulator. The truncated RgfA protein lacks the C-terminal DNA binding domain necessary for promoter binding and gene regulation. Here, we show that deletion ofrgfCin GBS strains lacking a functional RgfA increased systemic infection. Furthermore, infection with thergfCmutant increased induction of proinflammatory signaling pathwaysin vivo. Phosphoproteomic analysis revealed that 19 phosphopeptides corresponding to 12 proteins were differentially phosphorylated at aspartate, cysteine, serine, threonine, or tyrosine residues in thergfCmutant. This included aspartate phosphorylation of a tyrosine kinase, CpsD, and a transcriptional regulator. Consistent with this observation, microarray analysis of thergfCmutant indicated that >200 genes showed altered expression compared to the isogenic wild-type strain and included transcriptional regulators, transporters, and genes previously associated with GBS pathogenesis. Our observations suggest that in the absence of RgfA, nonspecific RgfC signaling affects the expression of virulence factors and GBS pathogenesis.
Monostotic Paget's disease of the second metacarpal
Authors: Cakmak Selami , Umur Levent , Keklikci Kenan , Rodop Osman
Published: January 2015

Paget's disease of the bone is a focal chronic disorder proceeding with elevated osteoblastic and osteoclastic activity in the affected area. The most common sites are pelvis, femur, lower lumbar vertebrae and skull. Monostotic disease is reported in 15–30% of all cases. We report a case of monostotic Paget's disease of the second metacarpal, which is a rare location even for polyostotic disease.
Biparietal variant of Alzheimer's disease: a rare presentation of a common disease
Authors: Marques Inês B , Tábuas-Pereira Miguel , Milheiro Miguel , Santana Isabel
Published: January 2015

Alzheimer's disease (AD) is a clinically heterogeneous disease that may have atypical presentations with focal cortical syndromes and relatively preserved episodic memory. The posterior variant of AD has two subtypes: occipitotemporal, presenting with visuoperceptive impairment, and biparietal, presenting with visuospatial dysfunction and apraxia. We report a case of a 51-year-old woman with progressive limb apraxia and choreiform movements. Her neuropsychological evaluation was compatible with dementia, and revealed ideomotor and ideational limb apraxia, severe visuoconstructive ability impairment, dyscalculia and posterior aphasia. Workup excluded metabolic, infectious, inflammatory or neoplastic causes, and hereditary conditions as Huntington's disease and familial AD. Cerebrospinal fluid biomarkers revealed β-amyloid reduction and τ protein increase. Brain imaging showed marked biparietal atrophy and hypoperfusion, and widespread cortical β-amyloid deposition. Biparietal variant of AD was diagnosed and acetylcholinesterase inhibitor treatment induced clinical stabilisation. AD may present with atypical features and a high clinical suspicion is necessary for an early diagnosis.
Double jeopardy: two episodes of forearm compartment syndrome in the same patient
Authors: Seth Rohit , Vijayan Roshan , Khandwala Asit
Published: January 2015

A 55-year-old woman taking warfarin for previous deep venous thrombosis (DVT), presented with an acutely swollen and painful forearm after forcefully contracting her forearm flexor compartment while using a car hand brake and later, an axe. Compartment syndrome was diagnosed and emergency fasciotomy performed, with a haematoma discovered between the flexor compartments of flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP). After evacuation and resolution of symptoms, the wounds were closed 4 days later. Following discharge on the fifth day, symptoms recurred without warning, prompting re-exploration and discovery of further haematoma. Symptoms again resolved and in due course a skin graft was applied to close the wound without tension.
A new score for the diagnosis of acute coronary syndrome in acute chest pain with non-diagnostic ECG and normal troponin
Authors: Boubaker Hamdi , Grissa Mohamed Habib , Beltaief Kaouther , Haj Amor Mohamed , Mdimagh Zouhaier , Boukhris Amor , Ben Amor Mehdi , Dridi Zohra , Letaief Mondher , Bouida Wahid , Boukef Riadh , Najjar Fadhel , Nouira Semir
Published: January 2015

Background

Acute coronary syndrome (ACS) represents a difficult diagnostic challenge in patients with undifferentiated chest pain. There is a need for a valid clinical score to improve diagnostic accuracy.

Objectives

To compare the performance of a model combining the Thrombolysis in Myocardial Infarction (TIMI) score and a score describing chest pain (ACS diagnostic score: ACSD score) with that of both scores alone in the diagnosis of ACS in ED patients with chest pain associated with a non-diagnostic ECG and normal troponin.

Methods

In this observational cohort study, we enrolled 809 patients admitted to a chest pain unit with normal ECG and normal troponin. They were prospectively evaluated in order to calculate TIMI score, chest pain characteristics score and ACSD score. Diagnosis of ACS was the primary outcome and defined on the basis of 2 cardiologists after reviewing the patient medical records and follow-up data. Mortality and major cardiovascular events were followed for 1 month for patients discharged directly from ED. Discriminative power of scores was evaluated by the area under the ROC curve.

Results

ACS was confirmed in 90 patients (11.1%). The area under the ROC curve for ACSD score was 0.85 (95% CI 0.80 to 0.90) compared with 0.74 (95% CI 0.67 to 0.81) for TIMI and 0.79 (95% CI 0.74 to 0.84) for chest pain characteristics score. A threshold value of 9 appeared to optimise sensitivity (92%) and negative predictive value (99%) without excessively compromising specificity (62%) and positive predictive value (23%).

Conclusions

The ACSD score showed a good discrimination performance and an excellent negative predictive value which allows safely ruling out ACS in ED patients with undifferentiated chest pain. Our findings should be validated in a larger multicentre study.
Transradial access in acute ischemic stroke intervention
Authors: Haussen Diogo C , Nogueira Raul G , DeSousa Keith G , Pafford Ryan N , Janjua Nazli , Ramdas Kevin N , Peterson Eric C , Elhammady Mohamed Samy , Yavagal Dileep R
Published: January 2015

Objective

To describe the feasibility and safety of transradial access (TRA) in the interventional management of acute ischemic stroke (AIS).

Methods

A retrospective review of the local institutional AIS interventional databases of three tertiary academic centers was performed and the use of TRA identified.

Results

TRA was attempted in 15 (1.5%) of 1001 patients; it was used in 12 cases due to transfemoral access (TFA) failure and in 3 as the primary strategy. The mean age was 72.3±8.6 and 46% were male. Baseline National Institutes of Health Stroke Scale score was 19.5±8.7, two patients (14%) received intravenous tissue plasminogen activator, and mean time from last known normal to intra-arterial therapy was 17.0±20.1 h. Five patients had anterior circulation occlusive disease and 10 had vertebrobasilar occlusions. TRA was effective in allowing clot engagement in 13 of 15 cases: one patient had a hypoplastic radial artery that precluded sheath advancement and one had chronic innominate artery occlusion that could not be crossed. Mean time to switch from TFA to TRA was 1.9±1.3 h and the mean time from radial puncture to reperfusion was 2.2±1.0 h. Modified Thrombolysis In Cerebral Infarction 2b–3 reperfusion via TRA was achieved in 9 of 15 patients (60%). No radial puncture site complications were noted. At 90 days, two patients (13%) had a good clinical outcome and seven (50%) had died.

Conclusions

Failure of TFA in the endovascular treatment of AIS is uncommon but leads to unacceptable delays in reperfusion and poor outcomes. Standardization of benchmarks for access switch could serve as a guide for neurointerventionalists. TRA is a valid approach for the endovascular treatment of AIS.
Initial experience with the PulseRider for the treatment of bifurcation aneurysms: report of first three cases in the USA
Authors: Spiotta Alejandro M , Chaudry M Imran , Turk Aquilla S , Turner Raymond D
Published: January 2015

Introduction

The PulseRider is a novel device intended for use in the treatment of aneurysms arising at bifurcations. We present the initial results of the first three cases in the USA employing the PulseRider device.

Methods

Aneurysms intended to be treated with the PulseRider device at a single institution were identified prospectively. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad-necked were considered candidates for treatment with the novel device.

Results

Patients were pretreated with dual antiplatelet therapy. All cases were performed under general endotracheal anesthesia. An appropriately sized PulseRider device was deployed across the neck of the aneurysm. A microcatheter was then navigated over a 0.014 inch microwire through the device into the aneurysm. Complete occlusion of the aneurysm was achieved in all cases without intraprocedural complications.

Conclusions

We have found in our early experience with the Pulse Rider device that its use is safe and effective as an adjunct in the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist.
Silica sulfuric acid magnetic nanoparticle: an efficient and ecofriendly catalyst for synthesis of spiro[2-amino-4H-pyran-oxindole]s
Authors: Karimi Ali Reza , Sourinia Meysam , Dalirnasab Zeinab , Karimi Marzie
Published: January 2015

Silica sulfuric acid magnetic nanoparticles efficiently catalyze the one-pot, three-component reaction of isatins and malononitrile with dimedone, 1,3-dimethylbarbituric acid or 4-hydroxycoumarin in EtOH–H2O to afford the corresponding spiro[2-amino-4H-pyran-oxindole] derivatives in high yields under ultrasound irradiation at 60 °C. The heterogeneous nanocatalyst could be recovered easily from the reaction mixture using an external magnet and reused many times without significant loss of its catalytic activity.