bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic Dentoalveolar and Maxillofacial Injuries in Cats
Authors: Soukup Jason W , Snyder Christopher J
Published: October 2014

Practical relevance:

Maxillofacial and traumatic dentoalveolar injuries can cause pain and inflammation, and reduce function of the mouth, impacting a cat’s quality of life. Many traumatically induced feline fractures have been reported to involve the mandible or skull and, in cats with maxillofacial trauma, traumatic dentoalveolar injuries are particularly prevalent. Traumatic dentoalveolar injuries can also often be found in otherwise healthy cats.

Clinical challenges:

Some traumatic dentoalveolar injuries require emergency treatment; timely recognition and managment is therefore important for achieving the optimal outcome. Multiple approaches exist for the management and repair of maxillofacial traumatic injuries. However, those for traumatic dentoalveolar injuries may be more limited.

Audience:

This review is aimed at feline and general practitioners, as well as veterinarians with expertise in dentistry.

Evidence base:

The authors draw on their clinical experience and evidence from the literature, where appropriate, to produce an overview of foundation guidelines. It is hoped that this will serve as a stimulus for deeper consideration as to what constitutes ‘best practice’ principles for cats with traumatic dentoalveolar and maxillofacial injuries.
Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis
Authors: Padmanabhan Anand , Jones Curtis G. , Bougie Daniel W. , Curtis Brian R. , McFarland Janice G. , Wang Demin , Aster Richard H.
Published: October 2014

Key Points

Platelet-activating, but not nonactivating, human HIT antibodies bind to and activate PF4-treated platelets. Activating antibodies may recognize subtle conformational changes induced in PF4 by chondroitin-4-sulfate, the major platelet glycosaminoglycan.
CDK6 as a key regulator of hematopoietic and leukemic stem cell activation
Authors: Scheicher Ruth , Hoelbl-Kovacic Andrea , Bellutti Florian , Tigan Anca-Sarmiza , Prchal-Murphy Michaela , Heller Gerwin , Schneckenleithner Christine , Salazar-Roa María , Zöchbauer-Müller Sabine , Zuber Johannes , Malumbres Marcos , Kollmann Karoline , Sexl Veronika
Published: October 2014

Key Points

CDK6 acts as a transcriptional regulator to suppress Egr1 in HSCs and LSCs, allowing their activation. Cdk6 −/− HSCs fail to contribute to repopulation in competitive transplants, and BCR-ABLp210+Cdk6−/− LSCs fail to inflict disease.
Three-step method for systematic lymphadenectomy in gastric cancer surgery using the ‘curettage and aspiration dissection technique’ with Peng’s multifunctional operative dissector
Authors: Wu Wenguang , Dong Ping , Wu Xiangsong , Li Maolan , Ding Qichen , Zhang Lin , Yang Jiahua , Weng Hao , Ding Qian , Tan Zhujun , Lu Jianhua , Gu Jun , Liu Yingbin
Published: October 2014

Background

Gastric cancer is one of the most common malignancies and is a leading cause of cancer death worldwide. Surgery is the most effective and successful method of treatment for gastric cancer, and systematic lymph node (LN) dissection is unquestionably the most effective procedure for treating LN metastases of gastric cancer. Systematic lymphadenectomy is the most important part of curative resection, but lymphadenectomy is also the most difficult procedure in gastric cancer surgery. The aim of this study is to report our three-step method for lymphadenectomy in gastric cancer.

Methods

In this study, the lymph node stations and groups were defined according to the 13th edition of the Japanese Classification for Gastric Carcinoma. The authors’ novel, simplified method consists of three steps: (1) the Kocher maneuver and dissection of the greater omentum together with the anterior sheet of the mesocolon, (2) dissection of the lesser omentum, and (3) lymphadenectomy following the main vessels. We primarily used Peng’s multifunctional operative dissector, which combines four different functions (cutting, separating, aspirating and coagulating). Our systematic lymphadenectomy included three steps, and the main procedure started from right to left and in the caudal to cranial direction.

Results

A total of 830 consecutive patients underwent our three-step-method systematic lymphadenectomy in advanced gastric cancer surgery. The mean operation time was 146 minutes, and the mean blood loss was 248 ml. The median postoperative hospital stay was 10.9 ± 4.8 days. The median number of examined LN was 31.6 (range 17 to 72) per patient, and the median number of metastatic LN was 5.6 (range 0 to 42) per patient. The overall incidence of postoperative complications was 10.6%, and the rate of hospital death was 0.9%. The overall three-year survival rate was 52.6%.

Conclusions

Our three-step method for lymphadenectomy is easy to perform and is a useful procedure for gastric cancer surgery.
Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms
Authors: Malmström Kristiina , Lehto Maili , Majuri Marja‐Leena , Paavonen Timo , Sarna Seppo , Pelkonen Anna S , Malmberg L Pekka , Lindahl Harry , Kajosaari Merja , Saglani Sejal , Alenius Harri , Mäkelä Mika J
Published: October 2014

Background

Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies.

Methods

Thirty‐nine infants (median age 0.9 years) underwent lung function testing by whole‐body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies.

Results

The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro‐inflammatory cytokine proteins IL‐1β, IL‐17A, IL‐18, IL‐23, and IL‐33 were found, whereas levels of Th2‐type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro‐inflammatory cytokine profile. Lung function did not correlate with any cytokine.

Conclusions

A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro‐inflammatory cytokines associated positively with frequent wheeze.
Delivery of fetus death with misoprostol in a pregnant woman with H7N9 avian influenza A virus pneumonia and ARDS
Authors: Guo Qiang , Zhao Daguo , Dong Fenglin , Liu Shenlan , Chen Youguo , Jin Jun , Fraidenburg Dustin R , Huang Jian-an
Published: October 2014

No abstract
Leptin induces upregulation of sphingosine kinase 1 in oestrogen receptor-negative breast cancer via Src family kinase-mediated, janus kinase 2-independent pathway
Authors: Alshaker Heba , Krell Jonathan , Frampton Adam E , Waxman Jonathan , Blyuss Oleg , Zaikin Alexey , Winkler Mathias , Stebbing Justin , Yagüe Ernesto , Pchejetski Dmitri
Published: October 2014

Introduction

Obesity is a known risk factor for breast cancer. Sphingosine kinase 1 (SK1) is an oncogenic lipid kinase that is overexpressed in breast tumours and linked with poor prognosis, however, its role in obesity-driven breast cancer was never elucidated.

Methods

Human primary and secondary breast cancer tissues were analysed for SK1 and leptin receptor expression using quantitative real-time polymerase chain reaction (qRT-PCR) assay. Leptin-induced signalling was analysed in human oestrogen receptor (ER)-positive and negative breast cancer cells using Western blotting, qRT-PCR and radiolabelling assays.

Results

Our findings show for the first time that human primary breast tumours and associated lymph node metastases exhibit a strong correlation between SK1 and leptin receptor expression (Pearson R = 0.78 and R = 0.77, respectively, P <0.001). Both these genes are elevated in metastases of ER-negative patients and show a significant increase in patients with higher body mass index (BMI). Leptin induces SK1 expression and activation in ER-negative breast cancer cell lines MDAMB-231 and BT-549, but not in ER-positive cell lines. Pharmacological inhibition and gene knockdown showed that leptin-induced SK1 activity and expression are mediated by activation of extracellular signal-regulated kinases 1/2 (ERK1/2) and Src family kinase (SFK) pathways, but not by the major pathways downstream of leptin receptor (LEPR) - janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Src-homology 2 domain-containing phosphatase 2 (SHP2) appeared to be key to SK1 activation, and may function as an adaptor protein between SFKs and LEPR. Importantly, leptin-induced breast cancer cell proliferation was abrogated by SK1-specific small interfering RNA (siRNA).

Conclusions

Overall, our findings demonstrate a novel SFK/ERK1/2-mediated pathway that links leptin signalling and expression of oncogenic enzyme SK1 in breast tumours and suggest the potential significance of this pathway in ER-negative breast cancer.
Ubiquitin-specific proteases as therapeutic targets for the treatment of breast cancer
Authors: Pal Anupama , Donato Nicholas J
Published: October 2014

Key mediators of signaling pathways in breast cancer involve post-translational protein modification, primarily mediated through phosphorylation and ubiquitination. While previous studies focused on phosphorylation events, more recent analysis suggests that ubiquitin plays a parallel and equally important role in several signaling and cell regulatory events in breast cancer. Availability of new tools capable of sensitive detection of gene mutations and aberrant expression of genes and proteins coupled with gene-specific knockdown and silencing protocols have provided insight into the previously unexplored ubiquitin regulatory process within these tumors. Ubiquitin-specific proteases are one class of enzymes with protein deubiquitinating activity, making up the majority of protein deubiquitinating diversity within mammalian cells. Ubiquitin-specific proteases are also emerging as potential therapeutic targets in many diseases, including cancer. In this report, we summarize the involvement of this class of enzymes in breast cancer signaling and cell regulation and illustrate the potential for additional studies to define novel targets and approaches in breast cancer therapy.
Improved characterization of medically relevant fungi in the human respiratory tract using next-generation sequencing
Authors: Bittinger Kyle , Charlson Emily S , Loy Elizabeth , Shirley David J , Haas Andrew R , Laughlin Alice , Yi Yanjie , Wu Gary D , Lewis James D , Frank Ian , Cantu Edward , Diamond Joshua M , Christie Jason D , Collman Ronald G , Bushman Frederic D
Published: October 2014

Background

Fungi are important pathogens but challenging to enumerate using next-generation sequencing because of low absolute abundance in many samples and high levels of fungal DNA from contaminating sources.

Results

Here, we analyze fungal lineages present in the human airway using an improved method for contamination filtering. We use DNA quantification data, which are routinely acquired during DNA library preparation, to annotate output sequence data, and improve the identification and filtering of contaminants. We compare fungal communities and bacterial communities from healthy subjects, HIV+ subjects, and lung transplant recipients, providing a gradient of increasing lung impairment for comparison. We use deep sequencing to characterize ribosomal rRNA gene segments from fungi and bacteria in DNA extracted from bronchiolar lavage samples and oropharyngeal wash. Comparison to clinical culture data documents improved detection after applying the filtering procedure.

Conclusions

We find increased representation of medically relevant organisms, including Candida, Cryptococcus, and Aspergillus, in subjects with increasingly severe pulmonary and immunologic deficits. We analyze covariation of fungal and bacterial taxa, and find that oropharyngeal communities rich in Candida are also rich in mitis group Streptococci, a community pattern associated with pathogenic polymicrobial biofilms. Thus, using this approach, it is possible to characterize fungal communities in the human respiratory tract more accurately and explore their interactions with bacterial communities in health and disease.
mirMark: a site-level and UTR-level classifier for miRNA target prediction
Authors: Menor Mark , Ching Travers , Zhu Xun , Garmire David , Garmire Lana X
Published: October 2014

MiRNAs play important roles in many diseases including cancers. However computational prediction of miRNA target genes is challenging and the accuracies of existing methods remain poor. We report mirMark, a new machine learning-based method of miRNA target prediction at the site and UTR levels. This method uses experimentally verified miRNA targets from miRecords and mirTarBase as training sets and considers over 700 features. By combining Correlation-based Feature Selection with a variety of statistical or machine learning methods for the site- and UTR-level classifiers, mirMark significantly improves the overall predictive performance compared to existing publicly available methods. MirMark is available from https://github.com/lanagarmire/MirMark.
Wastewater treatment using integrated anaerobic baffled reactor and Bio-rack wetland planted with Phragmites sp. and Typha sp.
Authors: Jamshidi Shervin , Akbarzadeh Abbas , Woo Kwang-Sung , Valipour Alireza
Published: October 2014

The purpose of this study is to examine the potential use of anaerobic baffled reactor (ABR) followed by Bio-rack wetland planted with Phragmites sp. and Typha sp. for treating domestic wastewater generated by small communities (751 mg COD/L, 500 SCOD mg/L, 348 mg BOD5/L). Two parallel laboratory-scale models showed that the process planted with Phragmites sp. and Typha sp. are capable of removing COD by 87% & 86%, SCOD by 90% & 88%, BOD5 by 93% & 92%, TSS by 88% & 86%, TN by 79% & 77%, PO4-P by 21% & 14% at an overall HRT of 21 (843 g COD/m3/day & 392 g BOD5/m3/day) and 27 (622 g COD/m3/day & 302 g BOD5/m3/day) hours, respectively. Microbial analysis indicated a high reduction in the MPN of total coliform and TVC as high as 99% at the outlet end of the processes. The vegetated system using Phragmites sp. showed significantly greater (p <0.05) pollutant removal efficiencies due to its extensive root and mass growth rate (p <0.05) of the plant compared to Typha sp. The Phragmites sp. indicated a higher relative growth rate (3.92%) than Typha sp. (0.90%). Microorganisms immobilized on the surface of the Bio-rack media (mean TVC: 2.33 × 107 cfu/cm2) were isolated, identified and observed using scanning electron microscopy (SEM). This study illustrated that the present integrated processes could be an ideal approach for promoting a sustainable decentralization, however, Phragmites sp. would be more efficient rather than Typha sp.
Characterization of B and plasma cells in blood, bone marrow, and secondary lymphoid organs of rhesus macaques by multicolor flow cytometry
Authors: Neumann Berit , Klippert Antonina , Raue Katharina , Sopper Sieghart , Stahl-Hennig Christiane
Published: October 2014

B cells, as an important part of the humoral immune response, are generated in the BM, migrate to secondary lymphoid organs, and upon activation, differentiate into antibody-producing memory B cells or plasma cells. Despite the pivotal roles that they play in different diseases, a comprehensive characterization in healthy rhesus macaques, which serve as valuable models for a variety of human diseases, is still missing. With the use of multiparameter flow cytometry, we analyzed B cells in BM collected from two locations, i.e., the iliac crest (BMca) and the femur (BMfem), PB, as well as secondary lymphoid organs of healthy rhesus macaques. We assessed the frequencies of immature and mature B cells, as well as CD19+ CD20– CD38+/++ CD138+/++ plasmablasts/plasma cells. Furthermore, we found site-specific differences in the expression of markers for B cell activation and proliferation, chemokine receptors and Igs, as well as the distribution of memory B cell subpopulations. As secondary lymphoid organs harbor the highest frequencies of naive B cells, expression of CD80, CD95, and Ki67 was lower compared with B cells in the periphery and BM, whereas expression of IgD, CXCR4 (CD184), and CCR7 (CD197) was higher. Interestingly, BMca differed from BMfem regarding frequencies of B cells, their expression of CD80 and CXCR4, T cells, and plasma cells. In summary, these data identify baseline values for the above-mentioned parameters and provide the foundation for future studies on B and plasma cells in different diseases.
Determining fractal dimension from nuclear magnetic resonance data in rocks with internal magnetic field gradients
Authors: Daigle Hugh , Johnson Andrew , Thomas Brittney
Published: October 2014

Pore size distributions in rocks may be represented by fractal scaling, and fractal descriptions of pore systems may be used for prediction of petrophysical properties such as permeability, tortuosity, diffusivity, and electrical conductivity. Transverse relaxation time ([Formula: see text]) distributions determined by nuclear magnetic resonance (NMR) measurements may be used to determine the fractal scaling of the pore system, but the analysis is complicated when internal magnetic field gradients at the pore scale are sufficiently large. Through computations in ideal porous media and laboratory measurements of glass beads and sediment samples, we found that the effect of internal magnetic field gradients was most pronounced in rocks with larger pores and a high magnetic susceptibility contrast between the pore fluid and mineral grains. We quantified this behavior in terms of pore size and Carr-Purcell-Meiboom-Gill (CPMG) half-echo spacing through scaling arguments. We additionally found that the effects of internal field gradients may be mitigated in the laboratory by performing [Formula: see text] measurements with different CPMG half-echo spacings and fitting the apparent fractal dimensions determined by the NMR measurements with a model to determine the true pore system fractal dimension.
Multidisciplinary approach in determining the best zone to land a Haynesville horizontal well
Authors: Liu Shujie , Zett Adrian , Spain David , Rabinovich Michael , Gillham Travis , Gangopadhyay Abhijit , Lucas Jennifer , Zhou Qiang , Gysen Alain
Published: October 2014

The Upper Jurassic Haynesville Shale Formation in the East Texas Basin, North America, is a black, organic-rich, calcareous mudstone that lies below the Bossier Shale and above the Cotton Valley Limestone. The reservoir quality was controlled by primary depositional process and secondary diagenesis. The best lithology type in terms of drilling, completion, and production is the organic-rich, silty calcareous mudstone with low clay content. The studied well traversed the entire Haynesville Formation with the objective to assess the production potential of this formation. We acquired open-hole, triple-combo logging while drilling (LWD) logs, two types of production logs, and regional microseismic data. Postdrill log modeling confirmed that the horizontal well stayed on the planned trajectory, based on the log correlation between the horizontal and offset wells. Log modeling demonstrated that the LWD resistivity logs in horizontal wells are subject to resistivity anisotropy and polarization horn effects. We integrated the production log results with the open-hole, log formation evaluation and mineralogy-based brittleness index, to understand the static reservoir properties and dynamic inflow performance. The open-hole and cased-hole logs consistently showed that the “rabbit ears” interval at the base of the Upper Haynesville and the top interval of the Upper Haynesville were excellent lateral well-landing zones for best production. We combined microseismic data with production log data and found that the effective stimulated rock volume by hydraulic fracturing was mostly concentrated in the top interval of the Upper Haynesville and the “rabbit ears” interval at the base of the Upper Haynesville. The study demonstrated that a multidisciplinary approach was necessary in determining the best zone to land Haynesville horizontal wells.
Homomonadology: Leo Bersani’s Essentialism
Authors: Tuhkanen Mikko
Published: October 2014

“Homomonadology” outlines the emergence and elaboration of Leo Bersani’s onto-ethics/aesthetics over the past half a century, focusing particularly on his interest in the shared references to Leibnizian metaphysics in twentieth-century philosophical and literary texts. The essay begins by detailing Bersani’s early engagement, in Balzac to Beckett: Center and Circumference in French Fiction (1970), with Marcel Proust and Samuel Beckett, as well as Gilles Deleuze’s and Maurice Blanchot’s commentaries on the two writers. Having borrowed Deleuze’s description of Proust as a “Leibnizian,” Bersani moves from the Proustian to the Beckettian text, organizing his reading in such later texts as Arts of Impoverishment (1993, cowritten with Ulysse Dutoit) around Beckett’s allusions to monadology. “Homomonadology” argues that the concept of the Leibnizian monad allows Bersani to articulate an onto-ethics of singularity and correspondences, of nonrelatedness and unity, in a way that comes to inform his post-1980s work on queer theory and queer ethics. It is Bersani’s commitment to ontology that renders his work, despite its influence on a number of fields, something of an anomaly in the contemporary critical field. With his varied sources—Deleuze, Proust, and Beckett among the most important—Bersani becomes, as he puts it in an interview, “an essentialist villain” in scholarly fields often driven by constructivist, antiessentialist imperatives.
Feminist Aesthetics: Transformative Practice, Neoliberalism, and the Violence of Formalism
Authors: Ziarek Ewa Plonowska
Published: October 2014

This essay develops further the main implications of a feminist theory of aesthetics and modernism first articulated in Feminist Aesthetics and the Politics of Modernism. By engaging critically with Theodor Adorno and Giorgio Agamben in the context of feminist theories of gender and race, the author examines complex relations between political and aesthetic transformations, stressing their relation to gender and race differences as well as the role of materiality in political contestation and aesthetic invention. The theory of feminist aesthetics discussed here traces what has been violently erased from history and asks how this erasure is inscribed in new possibilities for writing, sexuality, and being in the world. In particular, the essay stresses two central characteristics of feminist aesthetic practice in modernity. First, it reinterprets the endlessly replicated contradiction between feminist emancipatory struggles and gender/race melancholia—evident, for example, in current discussions of vulnerability and resilience, or negative and recuperative readings—as two inseparable dimensions of the transformative potential inherent in feminist aesthetic practices. Second, the essay stresses the relational character of women’s literature and artworks because the possibility of women’s aesthetic practice emerges from political intersubjective alliances; from the oscillation between loss and transformation; from gendered and racialized relations to the human and the nonhuman world; and from the contestation of gendered and racist violence of abstract formalism. Consequently, feminist aesthetics has to approach any artistic practice in nonindividualist, and even not entirely anthropocentric, terms. Only such a relational feminist approach to the impossibility and possibility of transformative artistic practices can offer resistance to art’s appropriation by the politics of modernity and contemporary neoliberalism.
Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions
Authors: Chakraborty Sandeep , Rao Basuthkar J. , Asgeirsson Bjarni , Dandekar Abhaya M.
Published: October 2014

Ebola, considered till recently as a rare and endemic disease, has dramatically transformed into a potentially global humanitarian crisis. The genome of Ebola, a member of the Filoviridae family, encodes seven proteins. Based on the recently implemented software (PAGAL) for analyzing the hydrophobicity and amphipathicity properties of alpha helices (AH) in proteins, we characterize the helices in the Ebola proteome. We demonstrate that AHs with characteristically unique features are involved in critical interactions with the host proteins. For example, the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain has an AH with a large hydrophobic moment. The ability of this AH to bind to other host proteins is disrupted by a neutralizing antibody derived from a human survivor of the 1995 Kikwit outbreak, emphasizing the critical nature of this secondary structure in the virulence of the Ebola virus. Our method ensures a comprehensive list of such `hotspots'. These helices probably are or can be the target of molecules designed to inhibit AH mediated protein-protein interactions. Further, by comparing the AHs in proteins of the related Marburg viruses, we are able to elicit subtle changes in the proteins that might render them ineffective to previously successful drugs. Such differences are difficult to identify by a simple sequence or structural alignment. Thus, analyzing AHs in the small Ebola proteome can aid rational design aimed at countering the `largest Ebola epidemic, affecting multiple countries in West Africa' (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html).
What Makes It Green? The Role of Centrality of Green Attributes in Evaluations of the Greenness of Products
Authors: Gershoff Andrew D. , Frels Judy K.
Published: October 2014

An increasing body of research addresses consumers' green product purchasing behavior, and yet little work has examined how consumers form perceptions of the greenness of products in the first place. Drawing on theories of attribute centrality (the degree to which an attribute is integral in defining an object), the authors argue that products with identical environmental benefits will be judged more or less green depending on whether the benefit stems from a central versus a peripheral attribute. They present four studies that support the hypotheses and explore factors that influence the effect of central attributes, including product category membership and integration of the green attribute with other elements of the product. They include controls for firm motivations and importance of the attribute to the individual consumer. The authors conclude the article with managerial and public policy implications, such as advice for firms on where to make green investments for maximum consumer impact and insight for public policy makers on the need for consumer assistance in objectively evaluating products with identical environmental benefits that achieve those benefits in different ways.
Shifting gears: industrial policy and automotive industry after the 2008 financial crisis
Authors: Oh Seung-Youn
Published: October 2014

Apart from being one of the hardest hit sectors during the 2008 financial crisis, the auto sector is also a prominent sector where emerging auto markets such as China have fared relatively well compared to their competitors in North America and Europe. This paper examines various ways that nations have shifted their policy gears to revive and restructure the automotive industry by using the case studies of the USA, France, and China. New sets of policy initiatives are contingent on particular industrial and institutional contexts, but both developed and developing countries have employed wide range of “murky” protectionist measures. This makes it unlikely for the WTO member countries to take a naming and shaming approach and file a case at the WTO level, which poses challenges to the WTO rules and trade liberalization.
Beta-casein nanocarriers of celecoxib for improved oral bioavailability
Authors: Perlstein Hadas , Bavli Yaelle , Turovsky Tanya , Rubinstein Abraham , Danino Dganit , Stepensky David , Barenholz Yechezkel
Published: October 2014

Beta-casein (bCN) micelles were developed as a platform for improved oral bioavailability (BA) of poorly water-soluble drugs. Here we demonstrate a proof-of-concept using the NSAID celecoxib (Cx) loaded into bCN micelles (Cx/bCN). In a crossover pharmacokinetic (PK) study in pigs (n=4), dosed intraduodenally with either the commercial Cx formulation Celebra
Changes in Public Opinion and the Occurrence of International Terrorism
Authors: Malečková Jitka , Stanišić Dragana
Published: October 2014

This paper is a contribution to the study of the impact of public opinion and evolutions in opinion on the occurrence of international terrorism. First, we replicate Krueger and Malečková’s (2009) model of the relationship between attitudes towards world leaders and occurrences of international terrorist incidents, using more recent data-the Gallup Survey data from 2010 on public opinion in Middle Eastern and North African countries and the National Counterterrorism Center (NCTC) data on international terrorism from 2009 to 2011. The analysis confirms the model of the earlier study, although, due to the distribution of terrorist incidents in the new sample, the evidence of the correlation between terrorist attacks and public opinion weakens. Second, we exercise an out-of-sample prediction of terrorist attacks using the estimated model based on the data from the 2004 to 2008 period to predict the occurrence of attacks in 2009–2011. The findings suggest that Krueger and Malečková’s (2009) model is unstable, either due to the instability of the process or the problematic nature of terrorism data. Further research is necessary to explain and test these results.
Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection
Authors: Ljubisavljevic Srdjan , Stojanovic Ivana
Published: October 2014

The role of nitrosative stress in the early pathogenesis of neuroinflammation and demyelination is undoubtedly wide. This review summarizes and integrates the results, found in previously performed studies, which have evaluated nitrosative stress participation in neuroinflammation. The largest number of studies indicates that the supply of nitrosative stress inhibitors has led to the opposite clinical effects in experimental studies. Some results claim that attributing the protective role to nitric oxide, outside the total changes of redox oxidative processes and without following the clinical and paraclinical correlates of neuroinflammation, is an overrated role of this mediator. The fact is that the use of nitrosative stress inhibitors would be justified in the earlier phases of neuroinflammation. The ideal choice would be a specific inducible nitric oxide synthase (iNOS) inhibitor, because its use would preserve the physiological features of nitric oxide produced by the effects of constitutive NOS. This review discusses the antinitrosative therapy as a potential mode of therapy that aims to control neuroinflammation in early phases, delaying its later phases, which are accompanied with irreversible neurological disabilities. Some parameters of nitrosative stress might serve as surrogate biomarkers for neuroinflammation intensity and its radiological and clinical correlates.
Temperature- and moisture-dependency of CsLiB6O10. A new phase, β-CsLiB6O10
Authors: Sennova Natalia A. , Cordier Gerhard , Albert Barbara , Filatov Stanislav K. , Bubnova Rimma S. , Isaenko Ludmila I. , Gubenko Lyubov I. , Klöckner Jan-Peter , Prosenc Marc H.
Published: October 2014

The structural behavior of the non-linear optical, nanoporous compound CsLiB6O10 was studied in a wide temperature range. Both the highly anisotropic thermal expansion of the borate with temperature variation and the deterioration of its crystals were investigated. The electron density distribution was analyzed in detail. A reversible, partial transition to a new modification, β-CsLiB6O10, was observed during cooling crystalline and moist samples of CsLiB6O10 to –25 °C. The crystal structure of the new phase is described.
Microstructure-Scale In-Situ Image Correlation-Based Study of Grain Deformation and Crack Tip Displacements in Al–Cu Alloys
Authors: Gupta Vipul K. , Willard Scott A. , Hochhalter Jacob D. , Smith Stephen W.
Published: October 2014

Mechanistic understanding based on experimental measurements of grain and crack tip deformation at relevant length scales is critical for improvement of physics-based modeling of microstructurally-sensitive fatigue crack propagation and for the computationally-assisted design of more durable materials. In this study, single-crystal, bi-crystal, and large-grain multi-crystal specimens of Al–Cu alloys are fabricated, characterized using electron backscattered diffraction (EBSD), and mechanically tested. In addition to conventional optic al–imaging based 3D image correlation (IC), scanning electron microscope (SEM) based high-resolution 2D IC is used to measure displacements within grain interiors, near crack tips, and grain boundaries. The use of micro-scale IC and EBSD-based experiments is discussed as they relate to the development of crystal-plasticity-based finite element models (CP–FEMs). This article specifically highlights experimental methods that have been developed to obtain the relevant data needed for CP–FEM calibration and validation.
Visceral adiposity index and DHEAS are useful markers of diabetes risk in women with polycystic ovary syndrome
Authors: Amato M C , Magistro A , Gambino G , Vesco R , Giordano C
Published: October 2014

Objective

On the basis of the known diabetes risk in polycystic ovary syndrome (PCOS), recent guidelines of the Endocrine Society recommend the use of an oral glucose tolerance test (OGTT) to screen for impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) in all women with PCOS. However, given the high prevalence of PCOS, OGTT would have a high cost–benefit ratio. In this study, we identified, through a receiver operating characteristic analysis, simple predictive markers of the composite endpoint (impaired fasting glucose (IFG) or IGT or IFG+IGT or T2DM) in women with PCOS according to the Rotterdam criteria.

Design

We conducted a cross-sectional study of 241 women with PCOS in a university hospital setting.

Methods

Clinical, anthropometric, and metabolic (including OGTT) parameters were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity, and the oral dispositional index and visceral adiposity index (VAI) were determined.

Results

Out of 241 women included in this study, 28 (11.6%) had an IFG, 13 (5.4%) had IGT, four (1.7%) had IFG+IGT, and four (1.7%) had T2DM. Among the anthropometric variables examined, the VAI had a significantly higher C-statistic compared with BMI (0.760 (95% CI: 0.70–0.81) vs 0.613 (95% CI: 0.54–0.67);P=0.014) and waist circumference (0.760 (95% CI: 0.70–0.81) vs 0.619 (95% CI: 0.55–0.68);P=0.028). Among all the hormonal and metabolic serum variables examined, DHEAS showed the highest C-statistic (0.720 (95% CI: 0.65–0.77);P<0.001).

Conclusions

In addition to fasting glucose, the VAI and DHEAS may be considered useful tools for prescreening in all women with PCOS without the classical risk factors for diabetes.
Uterine natural killer cells: supervisors of vasculature construction in early decidua basalis
Authors: Rätsep Matthew T , Felker Allison M , Kay Vanessa R , Tolusso Leandra , Hofmann Alexander P , Croy B Anne
Published: October 2014

Mammalian pregnancy involves tremendousde novomaternal vascular construction to adequately support conceptus development. In early mouse decidua basalis (DB), maternal uterine natural killer (uNK) cells oversee this process directing various aspects during the formation of supportive vascular networks. The uNK cells recruited to early implantation site DB secrete numerous factors that act in the construction of early decidual vessels (neoangiogenesis) as well as in the alteration of the structural components of newly developing and existing vessels (pruning and remodeling). Although decidual and placental development sufficient to support live births occur in the absence of normally functioning uNK cells, development and structure of implantation site are optimized through the presence of normally activated uNK cells. Human NK cells are also recruited to early decidua. Gestational complications including recurrent spontaneous abortion, fetal growth restriction, preeclampsia, and preterm labor are linked with the absence of human NK cell activation via paternally inherited conceptus transplantation antigens. This review summarizes the roles that mouse uNK cells normally play in decidual neoangiogenesis and spiral artery remodeling in mouse pregnancy and briefly discusses changes in early developmental angiogenesis due to placental growth factor deficiency.
A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans
Authors: Hawkins Edward G , Martin Ian , Kondo Lindsay M , Judy Meredith E , Brings Victoria E , Chan Chung-Lung , Blackwell GinaMari G , Bettinger Jill C , Davies Andrew G
Published: October 2014

Understanding the genes and mechanisms involved in acute alcohol responses has the potential to allow us to predict an individual’s predisposition to developing an alcohol use disorder. To better understand the molecular pathways involved in the activating effects of alcohol and the acute functional tolerance that can develop to such effects, we characterized a novel ethanol-induced hypercontraction response displayed by Caenorhabditis elegans. We compared body size of animals prior to and during ethanol treatment and showed that acute exposure to ethanol produced a concentration-dependent decrease in size followed by recovery to their untreated size by 40 min despite continuous treatment. An increase in cholinergic signaling, leading to muscle hypercontraction, is implicated in this effect because pretreatment with mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, blocked ethanol-induced hypercontraction, as did mutations causing defects in cholinergic signaling (cha-1 and unc-17). Analysis of mutations affecting specific subunits of nAChRs excluded a role for the ACR-2R, the ACR-16R, and the levamisole-sensitive AChR and indicated that this excitation effect is dependent on an uncharacterized nAChR that contains the UNC-63 α-subunit. We performed a forward genetic screen and identified eg200, a mutation that affects a conserved glycine in EAT-6, the α-subunit of the Na+/K+ ATPase. The eat-6(eg200) mutant fails to develop tolerance to ethanol-induced hypercontraction and remains contracted for at least 3 hr of continuous ethanol exposure. These data suggest that cholinergic signaling through a specific α-subunit-containing nAChR is involved in ethanol-induced excitation and that tolerance to this ethanol effect is modulated by Na+/K+ ATPase function.
Protein Kinases Are Associated with Multiple, Distinct Cytoplasmic Granules in Quiescent Yeast Cells
Authors: Shah Khyati H , Nostramo Regina , Zhang Bo , Varia Sapna N , Klett Bethany M , Herman Paul K
Published: October 2014

The cytoplasm of the eukaryotic cell is subdivided into distinct functional domains by the presence of a variety of membrane-bound organelles. The remaining aqueous space may be further partitioned by the regulated assembly of discrete ribonucleoprotein (RNP) complexes that contain particular proteins and messenger RNAs. These RNP granules are conserved structures whose importance is highlighted by studies linking them to human disorders like amyotrophic lateral sclerosis. However, relatively little is known about the diversity, composition, and physiological roles of these cytoplasmic structures. To begin to address these issues, we examined the cytoplasmic granules formed by a key set of signaling molecules, the protein kinases of the budding yeast Saccharomyces cerevisiae. Interestingly, a significant fraction of these proteins, almost 20%, was recruited to cytoplasmic foci specifically as cells entered into the G0-like quiescent state, stationary phase. Colocalization studies demonstrated that these foci corresponded to eight different granules, including four that had not been reported previously. All of these granules were found to rapidly disassemble upon the resumption of growth, and the presence of each was correlated with cell viability in the quiescent cultures. Finally, this work also identified new constituents of known RNP granules, including the well-characterized processing body and stress granule. The composition of these latter structures is therefore more varied than previously thought and could be an indicator of additional biological activities being associated with these complexes. Altogether, these observations indicate that quiescent yeast cells contain multiple distinct cytoplasmic granules that may make important contributions to their long-term survival.
The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients
Authors: Reddy Akhila , Yennurajalingam Sriram , Desai Hem , Reddy Suresh , Cruz Maxine , Wu Jimin , Liu Diane , Rodriguez Eden Mae , Waletich Jessica , Shin Seong Hoon , Gayle Vicki , Patel Pritul , Dalal Shalini , Vidal Marieberta , Tanco Kimberson , Arthur Joseph , Tallie Kimmie , Williams Janet , Silvestre Julio , Bruera Eduardo
Published: October 2014

Purpose.

Cancer pain management guidelines recommend initial treatment with intermediate-strength analgesics such as hydrocodone and subsequent escalation to stronger opioids such as morphine. There are no published studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the opioid rotation ratio (ORR) of hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients.

Patients and Methods.

We reviewed the records of consecutive patient visits at our supportive care center in 2011–2012 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected from patients who returned for follow-up within 6 weeks. Linear regression analysis was used to estimate the ORR between hydrocodone and MEDD. Successful OR was defined as 2-point or 30% reduction in the pain score and continuation of the new opioid at follow-up.

Results.

Overall, 170 patients underwent OR from hydrocodone to stronger opioid. The median age was 59 years, and 81% had advanced cancer. The median time between OR and follow-up was 21 days. We found 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow-up, the median ORR from hydrocodone to MEDD was 1.5 (quintiles 1–3: 0.9–2). The ORR was associated with hydrocodone dose (r = −.52; p < .0001) and was lower in patients receiving ≥40 mg of hydrocodone per day (p < .0001). The median ORR of hydrocodone to morphine was 1.5 (n = 44) and hydrocodone to oxycodone was 0.9 (n = 24).

Conclusion.

The median ORR from hydrocodone to MEDD was 1.5 and varied according to hydrocodone dose.
Low Socioeconomic Status Is Associated With More Aggressive End-of-Life Care for Working-Age Terminal Cancer Patients
Authors: Chang Chun-Ming , Wu Chin-Chia , Yin Wen-Yao , Juang Shiun-Yang , Yu Chia-Hui , Lee Ching-Chih
Published: October 2014

Background.

The relationship between low socioeconomic status (SES) and aggressiveness of end-of-life (EOL) care in cancer patients of working age (older than 18 years and younger than 65 years) is not clear. We assessed the association between aggressiveness of EOL care and differences in SES among working-age terminal cancer patients from Taiwan between 2009 and 2011.

Methods.

A total of 32,800 cancer deaths were identified from the Taiwan National Health Insurance Research Database. The indicators of aggressive EOL care (chemotherapy, more than one emergency room [ER] visit or hospital admission, more than 14 days of hospitalization, intensive care unit [ICU] admission, and death in an acute care hospital) in the last month of life were examined. The associations between SES and the indicators were explored.

Results.

Up to 81% of the cancer deaths presented at least one indicator of aggressive EOL care. Those who were aged 35–44 years and male, had low SES, had metastatic malignant disease, lived in urban areas, or were in hospitals with more abundant health care resources were more likely to receive aggressive EOL care. In multilevel logistic regression analyses, high-SES cancer deaths had less chemotherapy (p < .001), fewer ER visits (p < .001), fewer ICU admissions (p < .001), and lower rates of dying in acute hospitals (p < .001) compared with low-SES cancer deaths.

Conclusion.

Working-age terminal cancer patients in Taiwan received aggressive EOL care. EOL cancer care was even more aggressive in those with low SES. Public health strategies should continue to focus on low-SES patients to provide them with better EOL cancer care.
Una experiencia de simulación empresarial para el desarrollo de competencias profesionales
Authors: Peña Miguel Noemi , Sedano Hoyos Máximo
Published: October 2014

Los simuladores empresariales permiten transmitir contenidos, potenciar habilidades y competencias en gestión empresarial como herramientas formativas y educativas. En inglés son conocidos bajo el nombre de business games, los que a su vez son una modalidad deserious games. El propósito de este trabajo es analizar la potencialidad de un simulador empresarial como herramienta no solo formativa para promover el aprendizaje, sino también para potenciar capacidades y habilidades. En este sentido, la metodología utilizada se fundamenta en el análisis de una experiencia concreta de éxito en el uso de este simulador para el ámbito formativo como elemento dinamizador y catalizador para trabajar competencias en el entorno e-learning. En este análisis se detallará cómo se pueden trabajar dichas competencias en cada una de las fases de toma de decisiones del simulador empresarial llamado “Fórmula i”. El usuario debe gestionar una escudería de Fórmula 1 tratando de obtener los mejores resultados deportivos posibles a partir de una serie de decisiones tanto estratégicas como operativas. Finalmente, a través de un modelo econométrico de regresión de elaboración propia, se analizan los resultados obtenidos en su primera puesta en práctica para evaluar la influencia de esta metodología en la evaluación de la gestión de competencias de los recursos humanos en la empresa.