bluuebunny/crossref_metadata_2025 huggingface dataset:
Peer Mentoring Is Associated With Positive Change in Physical Activity and Aerobic Fitness of Grades 4, 5, and 6 Students in the Heart Healthy Kids Program
Authors: Spencer Rebecca A. , Bower Jenna , Kirk Sara F. L. , Hancock Friesen Camille
Published: April 2014

Only 7% of Canadian children achieve activity recommendations, contributing to obesity and preventable disease. The Heart Healthy Kids (H2K) program was designed to test the relationship between peer mentoring, physical activity, and cardiovascular fitness. Participants from 10 schools (5 control, 5 intervention) were enrolled in the program. In control schools, H2K included a physical activity challenge and education sessions. Intervention schools included the addition of a peer-mentoring component. Physical activity was measured through daily pedometer recording. Cardiovascular fitness was evaluated using the PACER (Progressive Aerobic Cardiovascular Endurance Run) protocol to calculate maximal oxygen uptake (VO2 max). Participants included 808 children (average age 9.9 ± 1.0 years). Although control and intervention schools did not differ at baseline, participants with peer mentoring logged significantly more steps per school day, on average, than those in control schools (6,785 ± 3,011 vs. 5,630 ± 2,586; p < .001). Male participants logged significantly more steps per school day than female participants. A significant improvement in VO2 max was also noted in intervention schools, with an average increase of 1.72 ml/mg/min. H2K was associated with positive change in physical activity and cardiovascular fitness, suggesting that peer mentoring shows promise for application in health promotion interventions.
Comment on “Measuring the Performance of Nations at Beijing Summer Olympics Using Integer-Valued DEA Model”
Authors: Wang Yang , Kakamu Kazuhiko
Published: April 2014

We correct the results by Wu et al. Although Wu et al. proposed an integer-valued data envelopment analysis (DEA) model, which is based on Charnes-Cooper-Rhodes (CCR) model, the displayed results are based on an integer-valued DEA model, which is based on Banker-Charnes-Cooper (BCC) model. Therefore, we introduce the true models and corresponding results.
Foreign-Born Voting Behavior in Local Elections
Authors: Goldsmith Melissa M. , Holzner Claudio A.
Published: April 2014

Approximately half of immigrants to the United States are now settling directly in cities and towns with little prior history of immigration. Because this dispersed settlement pattern is so recent, we know little about the political behavior of naturalized citizens in these new immigrant destinations. This article begins to fill this gap by exploring the determinants of foreign-born voting in municipal elections using a new dataset that combines official voting information from the state of Utah with demographic information about Utah residents from the Utah Population Database (UPDB). We hypothesize that in addition to individual-level predictors of prior experience with democratic politics and community attachment, the size of cities and their form of government will also affect the likelihood that foreign-born citizens will turn out to vote in local elections. We use multilevel modeling techniques to test these hypotheses and find that prior experience with democratic politics, whether in the United States or in their home country, along with the city-level characteristics of city size and form of government, are powerful predictors of foreign-born voting in local elections. Moreover, we find that while large cities experience lower levels of turnout for all citizens, the negative effect on participation is strongest for foreign-born citizens.
Psychometric Properties of the Dependence Scale in Large Randomized Clinical Trials of Patients With Mild and Moderate Alzheimer’s Disease
Authors: Wyrwich Kathleen W. , Auguste Priscilla , Buchanan Jacqui , Rudell Katja , Lacey Loretto , Leibman Christopher , Symonds Tara , Brashear H. Robert
Published: April 2014

Objective:

The need for assistance from others is a hallmark concern in Alzheimer’s disease (AD). The psychometric properties of the Dependence Scale (DS) for measuring treatment benefit were investigated in large randomized clinical trials of patients with mild to moderate AD.

Methods:

Reliability, validity, and responsiveness of the DS were examined. Path models appraised relationships and distinctiveness of key AD measures. The responder definition was empirically derived.

Results:

Generally acceptable reliability (α ≥ .65), significant ( P < .001) known-groups tests, and moderate to strong correlations ( r ≥ .31) confirmed the DS psychometric properties. Path models supported relationships and distinctiveness of key AD measures. A DS change of ≤1 point for patients with limited home care and ≤2 points for patients with assisted living care best described stability of the level of dependence on caregivers.

Conclusion:

The DS is a psychometrically robust measure in mild to moderate AD. The empirically derived responder definition aids in the interpretation of DS change.
Microphysiological modeling of the reproductive tract: A fertile endeavor
Authors: Eddie Sharon L , Kim J Julie , Woodruff Teresa K , Burdette Joanna E
Published: April 2014

Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs have led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling often referred to as ‘organ-on-a-chip’ or ‘human-on-a-chip’ places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology.
Increased knowledge of the effects of smoking and second-hand smoke encourages smoke-free homes
Authors: Fenton Brenda , Thankappan Kavumpurathu Raman , Champagne Beatriz , Lv Jun , Anthony Denis
Published: April 2014

Objective

To establish the drivers for smoke-free homes among current daily smokers.

Design

A cross-sectional study employing interviews (adults) and self-completed surveys (schoolchildren).

Sample

Children aged 12 and 14 in schools in four cities in China, India, Mexico and England. Adults in the community.

Measurements

Knowledge, attitude, beliefs and behaviour relevant to second-hand smoke in home.

Intervention

None.

Results

A total of 8994 adults and 14,756 children were surveyed. Knowledge of some of the effects of tobacco is high, but other effects are poorly understood in all cities. In Thiruvananthapuram, there is a lack of awareness of the addictiveness of tobacco, and Hangzhou has poor knowledge in general.

Conclusions

Messages about reducing tobacco usage are effective in support of smoke-free homes in the city with poorest knowledge (Hangzhou) but other factors are more important where knowledge is high.
Not All News Sources Are Equally Informative
Authors: Fraile Marta , Iyengar Shanto
Published: April 2014

Across a sample of twenty-seven European nations, we examine variation in the level of factual political knowledge in relation to self-reported exposure to news programs aired by public or commercial channels, and to broadsheet or tabloid newspapers. Unlike previous studies, we estimate the effects of exposure to these news outlets while controlling for self-selection into the audience. Our results show that the positive effects of exposure to broadsheets and public broadcasting on knowledge remain robust. Finally, we show that only exposure to broadsheets (and not to public broadcasting) narrows the knowledge gap within nations; relatively apathetic individuals who read broadsheet newspapers are able to “catch up” with their more attentive counterparts.
Dolutegravir: clinical efficacy and role in HIV therapy
Authors: Fantauzzi Alessandra , Mezzaroma Ivano
Published: April 2014

The human immunodeficiency virus type-1 (HIV-1) integrase enzyme has recently emerged as a primary alternative target to block viral replication, and integrase strand transfer inhibitors (INSTIs) are now considered an alternative ‘third agent’ class of antiretroviral (ARV) drugs. Dolutegravir is the first next-generation INSTI showing some novel and intriguing characteristics: it has a favorable pharmacokinetic profile with a prolonged intracellular halflife, rendering feasible a once daily dosing without the need for pharmacokinetic boosting. Secondly, it is largely metabolized via uridine diphosphate glucuronosyltransferase-1A1 with a minor component of cytochrome P450 isoforms, thus allowing a low grade of drug–drug interactions, so that its metabolic profile consents co-administration with the majority of the other ARV drugs without dose adjustments. Lastly, but no less important, virological studies have clearly demonstrated that dolutegravir has a significant activity against HIV-1 isolates showing raltegravir and/or elvitegravir associated resistance mutations. The attributes of once daily administration and the potential to treat INSTI-resistant viruses make dolutegravir an interesting and promising new agent in the treatment of both naïve and experienced HIV-1 subjects. In this review, the main concerns on dolutegravir efficacy are focused through the analysis of the currently available data from clinical studies in naïve and experienced patients, evaluating its possible place within the anti-HIV-1 drug armamentarium. The development of newer once daily, single tablet coformulations improved drug adherence and maximized the success of ARV therapy. Pharmacokinetic studies and dose-ranging trials suggested that dolutegravir is a good candidate for a single tablet regimen in one or more new coformulated pills that will be available in the near future.
There’s a religious app for that! A framework for studying religious mobile applications
Authors: Campbell Heidi A. , Altenhofen Brian , Bellar Wendi , Cho Kyong James
Published: April 2014

This article provides a new methodological approach to studying religious-oriented mobile applications available on the iTunes app store. Through an extensive review of 451 religious apps a number of problems were noted when relying solely on iTunes categories to identify app functions and purpose. Thus further analysis was done in order to present a new typology and framing of religious apps, which more accurately describe their design. We suggest that the 11 new categories offered here suggest a critical framework for studying religious apps. Thus this study provides a starting point for scholars interested in analyzing religious mobile applications to investigate how app developers integrate religious goals into their designs, and consider the primary ways people are expected to practice religion through mobile apps.
Digital orientations: “Ways of the hand” and practical knowing in media uses and other manual activities
Authors: Moores Shaun
Published: April 2014

This article is concerned with a particular aspect of the relationship between media and mobility. The author draws attention to what he calls the “doubly digital” quality of contemporary media—pointing to the intimate connection between movements through media settings (such as online environments) and movements of the fingers or digits on keyboards, keypads, touch-screens, and so on. His main interest is in mobile, generative ways of the hand that is at home with communication technologies, and in opening up an investigation of media uses as manual activities. In exploring these mobile, generative ways, he also reflects on a range of other manual activities that are apparently unrelated to media use—venturing into the disciplines of philosophy, sociology, and anthropology to discuss phenomenological perspectives on practices of typing, organ and piano playing, and plank sawing. Out of his exploration emerges a focus on embodied, sensuous, practical knowing, and on matters of orientation and habitation (with the author advocating a distinctive nonrepresentational, non-media-centric approach for future studies of media use in everyday life).
Correcting Network Failures: The Evolution of US Innovation Policy in the Wind and Advanced Battery Industries
Authors: Keller Matthew R. , Negoita Marian
Published: April 2014

Innovation and industrial policy debates typically focus on appropriate government responses to market and bureaucratic failures. However, recent research has suggested that in an era of decentralized, “network” production, effective governmental approaches to innovation policy should also consider “network failures” a central obstacle to innovative dynamism. We utilize the network failure concept to analyse past efforts of the United States (US) Government to stimulate innovation in the wind and advanced battery industries, and place ineffectual US efforts to galvanize these fields alongside historically more successful approaches in Denmark and Japan, respectively. The case analysis underscores the relevance of network failures to ineffective US attempts to stimulate technological dynamism, and suggests the importance of both general policy frameworks and case-specific “relational work” in forging or inhibiting industrial collaborations. Finally, we draw on recent data to suggest that though US policy justifications typically remain rooted in market and bureaucratic-centric languages, recent programs have often tacitly turned toward multi-faceted strategies to seed and support complex innovation networks.
The Global Gold Mining Industry: Materiality, Rent-Seeking, Junior Firms and Canadian Corporate Citizenship
Authors: Dougherty Michael L.
Published: April 2014

The growing incidence of conflicts between multinational gold mining companies and host community residents in the developing world is contextualized by discussing the recent proliferation of small, ‘junior’ companies in the gold mining industry. The geological attributes of the geographical distribution of gold deposits and gold's relative scarcity allow for an industry characterized by many small and intensely competitive firms. This competition plays out as a contest for access to resource and finance rents. Firms seek resource rents by investing in lax policy environments with mineralization that favours low-cost production, and firms seek finance rents by legally incorporating in Canada where equity financing for juniors is highly subsidized and corporate governance is lenient. Integrating studies on materiality, rent-seeking and the role of government incentives provides important insights into the rise of junior gold companies and the role of these firms in mineral conflicts around the world.
Can Differences in International Prices Measure Unequal Exchange in International Trade?
Authors: Subasat Turan
Published: April 2014

This article discusses the limitations of using the deviations in international prices as a measure of unequal exchange. It argues that international prices are formed in a complex manner and lower international prices for low income countries cannot simply be considered as evidence for unequal exchange. The empirical validity of the measure is also questionable.
Use of nickel(II) acetylacetonate and dimethylgold(III) acetylacetonate in gold on nickel plating
Authors: Gezerman A. O. , Çorbacıoğlu B. D.
Published: April 2014

This study investigates the use of non-toxic materials in nickel and gold plating baths that are used to plate gold on nickel plated stainless steel surfaces. The physical and mechanical stability and adhesion of the plating obtained using such compositions are investigated. The thickness, colour and adhesion of the plating have been studied using X-ray measurements, visible spectrometry and hydrogen embrittlement tests respectively. The plating baths employed in this study, which contained nickel(II) acetylacetonate and dimethylgold(III) acetylacetonate, were found to be good alternatives to conventional nickel and gold plating baths because they contain toxic nickel sulphate and cyanide salts.
Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia
Authors: Gagne Katelyn E. , Ghazvinian Roxanne , Yuan Daniel , Zon Rebecca L. , Storm Kelsie , Mazur-Popinska Magdalena , Andolina Laura , Bubala Halina , Golebiowska Sydonia , Higman Meghan A. , Kalwak Krzysztof , Kurre Peter , Matysiak Michal , Niewiadomska Edyta , Pels Salley , Petruzzi Mary Jane , Pobudejska-Pieniazek Aneta , Szczepanski Tomasz , Fleming Mark D. , Gazda Hanna T. , Agarwal Suneet
Published: April 2014

Key Points

PS can be overlooked in the differential diagnosis of children with severe congenital anemia. mtDNA deletion testing should be included in the genetic evaluation of patients with congenital anemia of unclear etiology.
SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury
Authors: Niswander Lisa M. , Fegan Katherine H. , Kingsley Paul D. , McGrath Kathleen E. , Palis James
Published: April 2014

Key Points

SDF-1 acutely affects megakaryocyte spatial distribution in the bone marrow at steady state and in the setting of radiation injury. SDF-1-directed localization of megakaryocytes into the vascular niche increases platelet output.
Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus
Authors: Schröder Wiebke , Bernhardt Jörg , Marincola Gabriella , Klein-Hitpass Ludger , Herbig Alexander , Krupp Guido , Nieselt Kay , Wolz Christiane
Published: April 2014

Background

It has been shown previously that aminocoumarin antibiotics such as novobiocin lead to immediate downregulation of recA expression and thereby inhibit the SOS response, mutation frequency and recombination capacity in Staphylococcus aureus. Aminocoumarins function by inhibiting the ATPase activity of DNA gyrase subunit B with a severe impact on DNA supercoiling.

Results

Here, we have analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. Using a novobiocin-resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and northern blot hybridisation revealed that the expression levels of a distinct set of genes were increased (e.g., recF-gyrB-gyrA, the rib operon and the ure operon) or decreased (e.g., arlRS, recA, lukA, hlgC and fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the level of supercoiling in S. aureus. Thus, downregulation of arlRS might partially compensate for the relaxing effect of novobiocin. Global analysis and gene mapping of supercoiling-sensitive genes did not provide any indication that they are clustered in the genome. Promoter fusion assays confirmed that the responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location.

Conclusions

The results indicate that the molecular properties of a given promoter, rather than the chromosomal topology, dictate the responsiveness to changes in supercoiling in the pathogen Staphylococcus aureus.
Protective factors against suicide among young-old Chinese outpatients
Authors: Chen Ying-Jen , Tsai Yun-Fang , Lee Shwu-Hua , Lee Hsiu-Lan
Published: April 2014

Background

Suicide is common among the elderly worldwide. However, no literature could be found on the beliefs/expectations that protect young-old people from attempting suicide. The purpose of this study was to explore young-old outpatients’ reasons for not killing themselves in Taiwan.

Method

Data for this qualitative descriptive study were extracted from a large research series. From the 83 elderly outpatients in the original sample, 31 were chosen for this study because they were young-old (65–74 years old) and from two randomly selected medical centers in northern Taiwan. Data on participants’ reasons for not killing themselves in unhappy situations were collected in individual interviews using a semi-structured guide and analyzed by content analysis.

Results

Analysis of interview data identified six major themes: satisfied with one’s life, suicide cannot resolve problems, fear of humiliating one’s children, religious beliefs, never thought about suicide, and living in harmony with nature.

Conclusion

These identified protective factors (reasons for living) could be added to suicide-prevention programs for the elderly. Our findings may also serve as a reference for geriatric researchers in western countries with increasing numbers of elderly ethnic minority immigrants.
Enhanced hypoglycemic effect of biotin-modified liposomes loading insulin: effect of formulation variables, intracellular trafficking, and cytotoxicity
Authors: Zhang Xingwang , Qi Jianping , Lu Yi , Hu Xiongwei , He Wei , Wu Wei
Published: April 2014

Peroral protein/peptide delivery has been one of the most challenging, but encouraging topics in pharmaceutics. This article was intended to explore the potential of biotin-modified liposomes (BLPs) as oral insulin delivery carriers. By incorporating biotin-DSPE into the lipid bilayer, we prepared BLPs using reverse evaporation/sonication method. We investigated hypoglycemic effects in normal rats after oral administration of BLPs, and the possible absorption mechanism by a series of in vitro tests. The relative pharmacological bioavailability of BLPs was up to 11.04% that was as much as 5.28 folds of conventional liposomes (CLPs). The results showed that the enhanced oral absorption of insulin mainly attributed to biotin ligand-mediated endocytosis. The results provided proof of BLPs as effective carriers for oral insulin delivery.
Detection of subtle neurological alterations by the Catwalk XT gait analysis system
Authors: Chen Ying-Ju , Cheng Fu-Chou , Sheu Meei-Ling , Su Hong-Lin , Chen Chun-Jung , Sheehan Jason , Pan Hung-Chuan
Published: April 2014

Background

A new version of the CatWalk XT system was evaluated as a tool for detecting very subtle alteration in gait based on higher speed sample rate; the system could also demonstrate minor changes in neurological function. In this study, we evaluated the neurological outcome of sciatic nerve injury intervened by local injection of hyaluronic acid. Using the CatWalk XT system, we looked for differences between treated and untreated groups and differences within the same group as a function of time so as to assess the power of the Catwalk XT system for detecting subtle neurological change.

Methods

Peripheral nerve injury was induced in 36 Sprague–Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of two groups: Group I: crush injury as the control; Group II: crush injury and local application with hyaluronic acid. These animals were subjected to neurobehavior assessment, histomorphology evaluation, and electrophysiology study periodically. These data were retrieved for statistical analysis.

Results

The density of neurofilament and S-100 over the distal end of crushed nerve showed significant differences either in inter-group comparison at various time points or intra-group comparison from 7 to 28 days. Neuronal structure architecture, axon counts, intensity of myelination, electrophysiology, and collagen deposition demonstrate significant differences between the two groups. There was significant difference of SFI and angle of ankle in inter- group analysis from 7 to 28 days, but there were no significant differences in SFI and angle of ankle at time points of 7 and 14 days. In the Cat Walk XT analysis, the intensity, print area, stance duration, and swing duration all showed detectable differences at 7, 14, 21, and 28 days, whereas there were no significant difference at 7 and 14 days with CatWalk 7 testing. In addition, there were no significant differences of step sequence or regularity index between the two versions.

Conclusion

Hyaluronic acid augmented nerve regeneration as early as 7 days after crush injury. This subtle neurological alteration could be detected through the CatWalk XT gait analysis but not the SFI, angle of ankle, or CatWalk 7 methods.
A Simplified Up-Down Method (SUDO) for Measuring Mechanical Nociception in Rodents Using von Frey Filaments
Authors: Bonin Robert P , Bories Cyril , De Koninck Yves
Published: April 2014

Background:

The measurement of mechanosensitivity is a key method for the study of pain in animal models. This is often accomplished with the use of von Frey filaments in an up-down testing paradigm. The up-down method described by Chaplan et al. (J Neurosci Methods 53:55–63, 1994) for mechanosensitivity testing in rodents remains one of the most widely used methods for measuring pain in animals. However, this method results in animals receiving a varying number of stimuli, which may lead to animals in different groups receiving different testing experiences that influences their later responses. To standardize the measurement of mechanosensitivity we developed a simplified up-down method (SUDO) for estimating paw withdrawal threshold (PWT) with von Frey filaments that uses a constant number of five stimuli per test. We further refined the PWT calculation to allow the estimation of PWT directly from the behavioral response to the fifth stimulus, omitting the need for look-up tables.

Results:

The PWT estimates derived using SUDO strongly correlated (r > 0.96) with the PWT estimates determined with the conventional up-down method of Chaplan et al., and this correlation remained very strong across different levels of tester experience, different experimental conditions, and in tests from both mice and rats. The two testing methods also produced similar PWT estimates in prospective behavioral tests of mice at baseline and after induction of hyperalgesia by intraplantar capsaicin or complete Freund's adjuvant.

Conclusion:

SUDO thus offers an accurate, fast and user-friendly replacement for the widely used up-down method of Chaplan et al.
TCMSP: a database of systems pharmacology for drug discovery from herbal medicines
Authors: Ru Jinlong , Li Peng , Wang Jinan , Zhou Wei , Li Bohui , Huang Chao , Li Pidong , Guo Zihu , Tao Weiyang , Yang Yinfeng , Xu Xue , Li Yan , Wang Yonghua , Yang Ling
Published: April 2014

Background

Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed.

Description

The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski’s rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development.

Conclusions

The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at http://sm.nwsuaf.edu.cn/lsp/tcmsp.php.
Micro‐patterned surfaces reduce bacterial colonization and biofilm formation in vitro: Potential for enhancing endotracheal tube designs
Authors: May Rhea M , Hoffman Matthew G , Sogo Melinda J , Parker Albert E , O’Toole George A , Brennan Anthony B , Reddy Shravanthi T
Published: April 2014

Background

Ventilator‐associated pneumonia (VAP) is a leading hospital acquired infection in intensive care units despite improved patient care practices and advancements in endotracheal tube (ETT) designs. The ETT provides a conduit for bacterial access to the lower respiratory tract and a substratum for biofilm formation, both of which lead to VAP. A novel microscopic ordered surface topography, the Sharklet micro‐pattern, has been shown to decrease surface attachment of numerous microorganisms, and may provide an alternative strategy for VAP prevention if included on the surface of an ETT. To evaluate the feasibility of this micro‐pattern for this application, the microbial range of performance was investigated in addition to biofilm studies with and without a mucin‐rich medium to simulate the tracheal environment in vitro.

Methods

The top five pathogens associated with ETT‐related pneumonia, Methicillin‐Resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Klebsiella pneumonia, Acinetobacter baumannii, and Escherichia coli, were evaluated for attachment to micro‐patterned and un‐patterned silicone surfaces in a short‐term colonization assay. Two key pathogens, MRSA and Pseudomonas aeruginosa, were evaluated for biofilm formation in a nutrient rich broth for four days and minimal media for 24 hours, respectively, on each surface type. P. aeruginosa was further evaluated for biofilm formation on each surface type in a mucin‐modified medium mimicking tracheal mucosal secretions. Results are reported as percent reductions and significance is based on t‐tests and ANOVA models of log reductions. All experiments were replicated at least three times.

Results

Micro‐patterned surfaces demonstrated reductions in microbial colonization for a broad range of species, with up to 99.9% (p < 0.05) reduction compared to un‐patterned controls. Biofilm formation was also reduced, with 67% (p = 0.12) and 52% (p = 0.05) reductions in MRSA and P. aeruginosa biofilm formation, respectively. Further, a 58% (p < 0.01) reduction was demonstrated on micro‐patterned surfaces for P. aeruginosa biofilms under clinically‐simulated conditions when compared to un‐patterned controls.

Conclusions

This engineered micro‐pattern reduces the colonization and biofilm formation of key VAP‐associated pathogens in vitro. Future application of this micro‐pattern on endotracheal tubes may prevent or prolong the onset of VAP without the need for antimicrobial agents.
Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages
Authors: Ye Liang , Wen Zhongyang , Li Yanqun , Chen Bingni , Yu Ting , Liu Lanying , Zhang Jinshun , Ma Yanmei , Xiao Shuying , Ding Liping , Li Li , Huang Zhong
Published: April 2014

Introduction

Our objective in the present study was to determine the signaling pathway of interleukin 10 (IL-10) for modulating IL-17 expression in macrophages and the importance of this mediation in collagen-induced arthritis (CIA).

Methods

IL-10-knockout (IL-10−/−) mice and wild-type (WT) mice were immunized with chicken type II collagen (CII) to induce arthritis. The expression levels of IL-17 and retinoid-related orphan receptor γt (RORγt) in macrophages and joint tissues of IL-10−/− and WT mice were analyzed by enzyme-linked immunosorbent assay, quantitative RT-PCR (qRT-PCR) and Western blotting. The F4/80 macrophages and positive IL-17-producing macrophages in synovial tissues of the mice were determined by immunohistochemistry. The populations of classically activated macrophage (M1) and alternatively activated macrophage (M2) phenotypes were analyzed by flow cytometry. The expression of genes associated with M1 and M2 markers was analyzed by qRT-PCR.

Results

Compared to WT mice, IL-10−/− mice had exacerbated CIA development, which was associated with increased production of T helper 17 cell (Th17)/Th1 proinflammatory cytokines and CII-specific immunoglobulin G2a antibody after CII immunization. Macrophages in IL-10−/− mice had increased amounts of IL-17 and RORγt compared with the amounts in WT mice with CIA. Immunofluorescence microscopy showed that the number of IL-17-producing macrophages in synovial tissues was significantly higher in IL-10−/− mice than in WT mice. IL-10 deficiency might promote macrophage polarization toward the proinflammatory M1 phenotype, which contributes to the rheumatoid arthritis inflammation response.

Conclusion

IL-10 inhibits IL-17 and RORγt expression in macrophages and suppresses macrophages toward the proinflammatory M1 phenotype, which is important for the role of IL-10 in mediating the pathogenesis of CIA.
Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study
Authors: Chen Yun-Xia , Li Chun-Sheng
Published: April 2014

Introduction

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores.

Methods

Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems.

Results

Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD.

Conclusions

The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.
Transcriptional dissection of pancreatic tumors engrafted in mice
Authors: Martinez-Garcia Raquel , Juan David , Rausell Antonio , Muñoz Manuel , Baños Natalia , Menéndez Camino , Lopez-Casas Pedro P , Rico Daniel , Valencia Alfonso , Hidalgo Manuel
Published: April 2014

Background

Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient-derived xenograft (PDX) models is a promising platform for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine tumor environment on the gene expression of the engrafted human tumoral cells.

Methods

We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data of 18 PDX models, 53 primary tumors and 41 cell lines from PDAC. The results obtained in the PDAC system were further compared with public available microarray data from 42 PDX models, 108 primary tumors and 32 cell lines from hepatocellular carcinoma (HCC). We developed a robust analysis protocol to explore the gene expression space. In addition, we completed the analysis with a functional characterization of PDX models, including if changes were caused by murine environment or by serial passing.

Results

Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable from each other based on their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models can be separated into two different groups that share some partial similarity with their corresponding original primary tumors. Our results point to the lack of human stromal involvement in PDXs as a major factor contributing to their differences from the original primary tumors. The main functional differences between pancreatic PDX models and human PDAC are the lower expression of genes involved in pathways related to extracellular matrix and hemostasis and the up- regulation of cell cycle genes. Importantly, most of these differences are detected in the first passages after the tumor engraftment.

Conclusions

Our results suggest that PDX models of PDAC and HCC retain, to some extent, a gene expression memory of the original primary tumors, while this pattern is not detected in conventional cancer cell lines. Expression changes in PDXs are mainly related to pathways reflecting the lack of human infiltrating cells and the adaptation to a new environment. We also provide evidence of the stability of gene expression patterns over subsequent passages, indicating early phases of the adaptation process.
Effects of enamel matrix derivative on the proliferation and osteogenic differentiation of human gingival mesenchymal stem cells
Authors: Wu Shu-Man , Chiu Hsien-Chung , Chin Yu-Tang , Lin Heng-Yi , Chiang Cheng-Yang , Tu Hsiao-Pei , Fu Martin MJ , Fu Earl
Published: April 2014

Introduction

Gingiva-derived mesenchymal stem cells (GMSCs) have recently been harvested and applied for rebuilding lost periodontal tissue. Enamel matrix derivative (EMD) has been used for periodontal regeneration and the formation of new cementum with inserting collagen fibers; however, alveolar bone formation is minimal. Recently, EMD has been shown to enhance the proliferation and mineralization of human bone marrow mesenchymal stem cells. Because the gingival flap is the major component to cover the surgical wound, the effects of EMD on the proliferation and mineralization of GMSCs were evaluated in the present study.

Methods

After single cell suspension, the GMSCs were isolated from the connective tissues of human gingiva. The colony forming unit assay of the isolated GMSCs was measured. The expression of stem cell markers was examined by flow cytometry. The cellular telomerase activity was identified by polymerase chain reaction (PCR). The osteogenic, adipogenic and neural differentiations of the GMSCs were further examined. The cell proliferation was determined by MTS assay, while the expression of mRNA and protein for mineralization (including core binding factor alpha, cbfα-1; alkaline phosphatase, ALP; and osteocalcin, OC; ameloblastin, AMBN) were analyzed by real time-PCR, enzyme activity and confocal laser scanning microscopy.

Results

The cell colonies could be easily identified and the colony forming rates and the telomerase activities increased after passaging. The GMSCs expressed high levels of surface markers for CD73, CD90, and CD105, but showed low expression of STRO-1. Osteogenic, adipogenic and neural differentiations were successfully induced. The proliferation of GMSCs was increased after EMD treatment. ALP mRNA was significantly augmented by treating with EMD for 3 hours, whereas AMBN mRNA was significantly increased at 6 hours after EMD treatment. The gene expression of OC was enhanced at the dose of 100 μg/ml EMD at day 3. Increased protein expression for cbfα-1 at day 3, for ALP at day 5 and 7, and for OC at week 4 after the EMD treatments were observed.

Conclusions

Human GMSCs could be successfully isolated and identified. EMD treatments not only induced the proliferation of GMSCs but also enhanced their osteogenic differentiation after induction.
Reduced consumption of protein-rich foods follows immune challenge in a polyphagous caterpillar
Authors: Mason Peri A. , Smilanich Angela M. , Singer Michael S.
Published: April 2014

Advances in ecological immunity have illustrated that, like vertebrates, insects exhibit adaptive immunity, including induced changes in feeding behavior that aid the immune system. In particular, recent studies have pointed to the importance of protein intake in mounting an immune response. In this study, we tested the hypothesis that the polyphagous caterpillar, Grammia incorrupta (Hy. Edwards, Erebidae), would adaptively change its feeding behavior in response to immune challenge, predicting that caterpillars would increase their intake of dietary protein. We further predicted that this response would enhance the melanization response, a component of the immune system that acts against parasitoids. We challenged the immune system using either tachinid fly parasitoids or a bead injection technique that has been used in studies to simulate parasitism, and measured feeding before and after immune challenge on diets varying in their macronutrient content. To evaluate the effects of diet on melanization, we quantified melanization of beads following feeding assays. Contrary to our prediction, we found that parasitized or injected caterpillars given a choice between high and low protein foods reduced their intake of the high protein food. Furthermore, in a no-choice experiment, caterpillars offered food with a protein concentration that is optimal for growth reduced feeding following immune challenge, whereas those offered a low protein food did not. Although variation in protein intake did not change caterpillars' melanization response, increased carbohydrate intake did increase melanization, suggesting a prophylactic role for carbohydrates. We discuss alternative mechanisms by which variation in protein intake could negatively or positively affect parasitized caterpillars, including nutritional interactions with the caterpillar's self-medication response.
Energy metabolism and regeneration impaired by seawater acidification in the infaunal brittlestar,Amphiura filiformis
Authors: Hu Marian Y. , Casties Isabel , Stumpp Meike , Ortega-Martinez Olga , Dupont Sam T.
Published: April 2014

Seawater acidification due to anthropogenic release of CO2 as well as the potential leakage of pure CO2 from sub-seabed carbon capture storage sites (CCS) may impose a serious threat to marine organisms. Although infaunal organisms can be expected to be particularly impacted by decreases in seawater pH, due to naturally acidified conditions in benthic habitats, information regarding physiological and behavioral responses is still scarce. Determination of pO2 and pCO2 gradients within the burrows of the brittlestar Amphiura filiformis during environmental hypercapnia demonstrated that besides hypoxic conditions, increases of environmental pCO2 are additive to the already high pCO2 (up to 0.08 kPa) within the burrows. In response to up to 4 weeks exposure to pH 7.3 (0.3 kPa pCO2) and pH 7.0 (0.6 kPa pCO2), metabolic rates of A.filiformis were significantly reduced in pH 7.0 treatments accompanied by increased ammonium excretion rates. Gene expression analyses demonstrated significant reductions of acid-base (NBCe and AQP9) and metabolic (G6PDH, LDH) genes. Determination of extracellular acid-base status indicated an uncompensated acidosis in CO2 treated animals, which could explain depressed metabolic rates. Metabolic depression is associated with a retraction of filter feeding arms into sediment burrows. Regeneration of lost arm tissues following traumatic amputation is associated with significant increases in metabolic rate, and hypercapnic conditions (pH 7.0, 0.6 KPa) dramatically reduce the metabolic scope for regeneration reflected in 80% reductions in regeneration rate. Thus, the present work demonstrates that elevated seawater pCO2 significantly affects the environment and the physiology of infaunal organisms like A. filiformis.
Diurnal dung beetles use the intensity gradient and the polarization pattern of the sky for orientation
Authors: el Jundi Basil , Smolka Jochen , Baird Emily , Byrne Marcus J. , Dacke Marie
Published: April 2014

To escape competition at the dung pile, a ball-rolling dung beetle forms a piece of dung into a ball and rolls it away. To ensure an their efficient escape from the dung pile, the beetles rely on a celestial compass to move along a straight paths. Here, we analyzed the reliability of different skylight cues for this compass and found that dung beetles rely not only on the sun, but also on the skylight polarization pattern. Moreover, we show the first evidence of an insect using the celestial light intensity gradient for orientation. Using a polarizer, we manipulated skylight so that the polarization pattern appeared to turn by 90°. The beetles then changed their bearing close to the expected 90°. This behavior was abolished if the sun was visible to the beetle, suggesting that polarized light is hierarchically subordinate to the sun. If the sky was depolarized and the sun was invisible, the beetles could still move along straight paths. We therefore analyzed the use of the celestial intensity gradient for orientation. Artificially rotating the intensity pattern by 180° caused beetles to orient in the opposite direction. The intensity cue was also found to be subordinate to the sun, and could play a role in disambiguating the polarization signal, especially at low sun elevations.