bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers in acute kidney injury – pathophysiological basis and clinical performance
Authors: Schrezenmeier E. V. , Barasch J. , Budde K. , Westhoff T. , Schmidt‐Ott K. M.
Published: August 2016

Various biomarkers of acute kidney injury (AKI) have been discovered and characterized in the recent past. These molecules can be detected in urine or blood and signify structural damage to the kidney. Clinically, they are proposed as adjunct diagnostics to serum creatinine and urinary output to improve the early detection, differential diagnosis and prognostic assessment of AKI. The most obvious requirements for a biomarker include its reflection of the underlying pathophysiology of the disease. Hence, a biomarker of AKI should derive from the injured kidney and reflect a molecular process intimately connected with tissue injury. Here, we provide an overview of the basic pathophysiology, the cellular sources and the clinical performance of the most important currently proposed biomarkers of AKI: neutrophil gelatinase‐associated lipocalin (NGAL), kidney injury molecule‐1 (KIM‐1), liver‐type fatty acid‐binding protein (L‐FABP), interleukin‐18 (IL‐18), insulin‐like growth factor‐binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP‐2) and calprotectin (S100A8/9). We also acknowledge each biomarker's advantages and disadvantages as well as important knowledge gaps and perspectives for future studies.
Population pharmacokinetics and analgesic potency of oxycodone
Authors: Choi Byung‐Moon , Lee Yong‐Hun , An Sang‐Mee , Lee Soo‐Han , Lee Eun‐Kyung , Noh Gyu‐Jeong
Published: August 2016

Aims

This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra‐abdominal surgery.

Methods

In the pharmacokinetic study, patients were administered intravenous oxycodone (0.1 mg kg−1), and arterial blood was sampled at pre‐set intervals. In the analgesic‐potency study, patients were administered intravenous oxycodone (0.1 mg kg−1) 30 min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as ≥3 or ≥5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2 mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient.

Results

In the population pharmacokinetic study (n = 54), oxycodone plasma concentration over time was well described by a three‐compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic‐potency study (n = 50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2–42.8) and 74.1 (29.2–128.3) ng ml−1 (first measurements) and 63.4 (15.6–120.1) and 76.1 (32.9–132.7) ng ml−1 (second measurements), respectively.

Conclusions

In major intra‐abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75 ng ml−1 and 60 ng ml−1, respectively.
Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time
Authors: Muth Christiane , Schröck Katharina , Madore Charlotte , Hartmann Kristin , Fanek Zain , Butovsky Oleg , Glatzel Markus , Krasemann Susanne
Published: August 2016

Prion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrPC) into a misfolded isoform (PrPSc) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases; however, their impact on prion disease pathophysiology is unclear with both beneficial PrPSc‐clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology. Here, the degree of microglia activation in the brain of prion infected mice with and without an additional intraperitoneal retrovirus infection was studied. Peripheral murine retrovirus infection leads to activation of parenchymal microglia without recruitment of monocytes. This activation correlated with transient clearance or delay in accumulation of infectious prions specifically from the brain at early time points in the diseases course. Microglia expression profiling showed upregulation of genes involved in protein degradation coinciding with prion clearance. This enforces a concept where microglia act beneficial in prion disease if adequately activated. Once microglia activation has ceased, prion disease reemerges leading to disease kinetics undistinguishable from the situation in prion‐only infected mice. This might be caused by the loss of microglial homeostatic function at clinical prion disease.
Synergistic activity of Card11 mutant and Bcl6 in the development of diffuse large B‐cell lymphoma in a mouse model
Authors: Takahara Taishi , Matsuo Keitaro , Seto Masao , Nakamura Shigeo , Tsuzuki Shinobu
Published: August 2016

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma; it derives from germinal center B cells. Although DLBCL harbors many genetic alterations, synergistic roles between such alterations in the development of lymphoma are largely undefined. We previously established a mouse model of lymphoma by transplanting gene‐transduced germinal center B cells into mice. Here, we chose one of the frequently mutated genes in DLBCL, Card11 mutant, to explore its possible synergy with other genes, using our lymphoma model. Given that BCL6 and BCL2 expression and/or function are often deregulated in human lymphoma, we examined the possible synergy between Card11, Bcl6, and Bcl2. Germinal center B cells were induced in vitro, transduced with Card11 mutant, Bcl6, and Bcl2, and transplanted. Mice rapidly developed lymphomas, with exogenously transduced Bcl2 being dispensable. Although some mice developed lymphoma in the absence of transduced Bcl6, the absence was compensated by elevated expression of endogenous Bcl6. Additionally, the synergy between Card11 mutant and Bcl6 in the development of lymphoma was confirmed by the fact that the combination of Card11 mutant and Bcl6 caused lymphoma or death significantly earlier and with higher penetrance than Card11 mutant or Bcl6 alone. Lymphoma cells expressed interferon regulatory factor 4 and PR domain 1, indicating their differentiation toward plasmablasts, which characterize activated B cell‐like DLBCL that represents a clinically aggressive subtype in humans. Thus, our mouse model provides a versatile tool for studying the synergistic roles of altered genes underlying lymphoma development.
Inhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells
Authors: Guo Wei , Wang Yu , Wang Zhu , Wang Yan‐Ping , Zheng Hong
Published: August 2016

Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor‐suppressing. Thus we studied MDA‐MB‐231 and SK‐BR‐3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI‐triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria. This inhibition increased mitochondrial cytochrome C release which augmented epirubicin‐induced caspase‐dependent apoptosis and cytotoxicity. In addition, the lysosomal neutralizing agent ammonia chloride (AC), and Atg7 knockdown by siRNA, could inhibit epirubicin‐triggered autophagy, enhance cytotoxicity, and increase caspase‐9‐ and caspase‐3‐dependent apoptosis. Thus, autophagy plays a prosurvival role in EPI‐treated MDA‐MB‐231 and SK‐BR‐3 cells, and autophagy inhibition can potentially reverse this effect and increase the cytotoxicity of EPI.
Seroprevalence of Toxoplasma gondii in Iranian patients with idiopathic Parkinson's disease
Authors: Ramezani Mahtab , Shojaii Maziar , Asadollahi Marjan , Karimialavijeh Ehsan , Gharagozli Koorosh
Published: August 2016

Objective

The aim of this research was to investigate the hypothesized association between Toxoplasma gondii infection and idiopathic Parkinson's disease (IPD).

Methods

In the present cross‐sectional study, we investigated T. gondii seropositivity in IPD patients in comparison with patients suffering from other neurological diseases (excluding movement disorders) and healthy people. Initially, all participants underwent a thorough clinical and paraclinical investigation. After this, 5 mL of blood was taken from all participants, and sera were tested for immunoglobulin M and immunoglobulin G (IgG) anti‐toxoplasma antibodies.

Results

A total of 41 IPD patients, 69 patients with other neurological diseases (excluding movement disorders) comprising 40 stroke patients, 10 epilepsy patients, 10 Alzheimer's disease patients and nine with chronic headaches, and 40 healthy people were investigated. All participants were matched in regard to sex, age and socioeconomic status. The frequency of anti‐toxoplasmosis seropositivity and the levels of IgG antibodies were significantly higher in the IPD patients (82.5%), in comparison with healthy participants (65%) and patients with neurological disease (65.2%; P = 0.01).

Conclusion

The present findings support the hypothesis of a probable association between T. gondii infection and IPD.
Relationship between damage‐associated molecular patterns and cytokines in myasthenia gravis
Authors: Uzawa Akiyuki , Kanai Tetsuya , Kawaguchi Naoki , Oda Fumiko , Ozawa Yukiko , Himuro Keiichi , Kuwabara Satoshi
Published: August 2016

Objective

Damage‐associated molecular patterns (DAMP) and cytokines can play a crucial role in inflammation at neuromuscular junctions in myasthenia gravis (MG). However, the relationship between DAMP and cytokine levels in MG pathogenesis remains unknown. To clarify this, we examined the relationship between serum levels of DAMP and cytokines in MG patients.

Methods

Using serum data from 26 patients with anti‐acetylcholine receptor antibody‐positive MG, we investigated the relationship between the levels of DAMP (high‐mobility group box 1 [HMGB1] and peroxiredoxin 5) and cytokines (interleukin [IL]‐4, IL‐15, IL‐19, IL‐20, IL‐28A, IL‐35, a proliferation‐inducing ligand [APRIL] and vascular endothelial growth factor), which were reported to be significantly elevated in MG.

Results

Serum levels of APRIL (r = 0.4789, P = 0.0133), IL‐19 (r = 0.5496, P = 0.0036) and IL‐35 (r = 0.5396, P = 0.0044) were correlated with those of HMGB1, but no cytokine levels were correlated with peroxiredoxin 5 levels. When we carried out multivariate analyses, only APRIL (P = 0.0244) and IL‐19 (P = 0.0009) levels were correlated with HMGB1 levels.

Conclusions

HMGB1 might be related with upregulation of IL‐19 and APRIL levels in MG immunopathogenesis. These molecules could play a key role in controlling autoimmune inflammatory response, and represent a potent therapeutic target in MG.
Frequency of peri‐implant diseases and associated factors
Authors: Gurgel Bruno César de Vasconcelos , Montenegro Sheyla Christine Lira , Dantas Poliana Medeiros Cunha , Pascoal Ana Luísa de Barros , Lima Kenio Costa , Calderon Patrícia dos Santos
Published: August 2016

Objective

To evaluate the frequency of peri‐implant diseases and factors associated with its occurrence.

Material and methods

One hundred and fifty‐five patients with dental implants were evaluated in this cross‐sectional study. Dental implants were clinically and radiographically evaluated to diagnose their peri‐implant condition, according to Mombelli (Proceedings of the 3rd European Workshop on Periodontology, 1999, Quintessence, London). Associations between peri‐implant diseases and independent variables (socioeconomic, demographic and periodontal characteristics) were evaluated through bivariate analysis with chi‐squared and Fisher's exact tests, as well as by multiple logistic regression. The significance level was set at 5%.

Results

The frequencies of the peri‐implant diseases, mucositis and peri‐implantitis, in individuals were 54% and 28% (CI, 95%), respectively. The sample was almost exclusively of patients with untreated periodontal disease (93%). Bivariate analysis showed that these peri‐implant diseases were associated with male patients (prevalence ratio [PR], 3.38), medication use (PR, 2.94), systemic diseases (PR, 2.25), number of implants (PR, 2.53), visible plaque index (PR, 2.49) and gingival index (PR, 2.70). Multiple logistic regression analysis showed that medication use (prevalence ratio adjusted [PRadj], 1.23; 95% CI: 1.04–1.46; P = 0.017), having two or more implants (PRadj, 1.22; 95% CI: 1.02–1.46; P = 0.029) and gingival bleeding index > 10% (PRadj, 1.22; 95% CI: 1.03–1.44; P = 0.022) were associated with the presence of peri‐implant disease.

Conclusion

Peri‐implant diseases were diagnosed in 54% of patients; gingival index of greater than 10%, having more than two implants and use of medication were associated with the frequency of peri‐implant disease.
Persistent Disparities between Recent Rates of Habitat Conversion and Protection and Implications for Future Global Conservation Targets
Authors: Watson James E.M. , Jones Kendall R. , Fuller Richard A. , Marco Moreno Di , Segan Daniel B. , Butchart Stuart H.M. , Allan James R. , McDonald‐Madden Eve , Venter Oscar
Published: August 2016

Anthropogenic conversion of natural habitats is the greatest threat to biodiversity and one of the primary reasons for establishing protected areas (PAs). Here, we show that PA establishment outpaced habitat conversion between 1993 and 2009 across all biomes and the majority (n= 567, 71.4%) of ecoregions globally. However, high historic rates of conversion meant that 447 (56.2%) ecoregions still exhibit a high ratio of conversion to protection, and of these, 127 (15.9%) experienced further increases in this ratio between 1993 and 2009. We identify 41 “crisis ecoregions” in 45 countries where recent habitat conversion is severe and PA coverage remains extremely low. While the recent growth in PAs is a notable conservation achievement, international conventions and associated finance mechanisms should prioritize areas where habitat is being lost rapidly relative to protection, such as the crisis ecoregions identified here.
Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach
Authors: Wadia Subeer Kanwar , Shah Trushil G. , Hedstrom Grady , Kovach Julie A. , Tandon Rajive
Published: August 2016

Purpose

Right ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS.

Methods

We retrospectively measured changes in the following RV parameters from a pre‐ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift.

Results

Over 24 months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4 mm pre‐ARDS to 16.3 mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67 m/s pre‐ARDS to 3.31 m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre‐ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO2/FiO2 ratios), P=.004, and was lower among 30‐day nonsurvivors compared with survivors, P=.002.

Conclusions

Mild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality.
Habitat selection by a large herbivore at multiple spatial and temporal scales is primarily governed by food resources
Authors: Dupke Claudia , Bonenfant Christophe , Reineking Björn , Hable Robert , Zeppenfeld Thorsten , Ewald Michael , Heurich Marco
Published: August 2016

Habitat selection can be considered as a hierarchical process in which animals satisfy their habitat requirements at different ecological scales. Theory predicts that spatial and temporal scales should co‐vary in most ecological processes and that the most limiting factors should drive habitat selection at coarse ecological scales, but be less influential at finer scales. Using detailed location data on roe deer Capreolus capreolus inhabiting the Bavarian Forest National Park, Germany, we investigated habitat selection at several spatial and temporal scales. We tested 1) whether time‐varying patterns were governed by factors reported as having the largest effects on fitness, 2) whether the trade‐off between forage and predation risks differed among spatial and temporal scales and 3) if spatial and temporal scales are positively associated. We analysed the variation in habitat selection within the landscape and within home ranges at monthly intervals, with respect to land‐cover type and proxys of food and cover over seasonal and diurnal temporal scales. The fine‐scale temporal variation follows a nycthemeral cycle linked to diurnal variation in human disturbance. The large‐scale variation matches seasonal plant phenology, suggesting food resources being a greater limiting factor than lynx predation risk. The trade‐off between selection for food and cover was similar on seasonal and diurnal scale. Habitat selection at the different scales may be the consequence of the temporal variation and predictability of the limiting factors as much as its association with fitness. The landscape of fear might have less importance at the studied scale of habitat selection than generally accepted because of the predator hunting strategy. Finally, seasonal variation in habitat selection was similar at the large and small spatial scales, which may arise because of the marked philopatry of roe deer. The difference is supposed to be greater for wider ranging herbivores.
NicheMapR – an R package for biophysical modelling: the microclimate model
Authors: Kearney Michael R. , Porter Warren P.
Published: August 2016

Microclimatic variables are necessary for a wide range of pure and applied problems in environmental science. In ecology, microclimatic conditions are prerequisites for modelling the heat and water budgets of organisms, from which climatic constraints on behaviour, life histories, distribution and abundance can be inferred. Despite the critical importance of microclimates, there is no general‐purpose, accessible microclimate model available for use in ecological studies.

Here we introduce and document the microclimate model of the biophysical modelling package NicheMapR, an R package that includes a suite of programs for mechanistic modelling of heat and mass exchange between organisms and their environments. The NicheMapR microclimate model is based on a Fortran program originally developed by Porter, Mitchell, Beckman and McCullough for predicting hourly above‐ and below‐ground conditions from meteorological, terrain, vegetation and soil data. The model includes routines for computing solar radiation, including effects of shading, slope, aspect and horizon angles (hillshade), and can include variable substrate properties with depth.

Here we configure the program to be called from R as part of the NicheMapR package, and describe the model in detail including new functionality for modelling soil water balance and snow, optional input of hourly or daily weather input data, and an R implementation of the Global Aerosol Data Set for obtaining local estimates of aerosol profiles as input to the model. We include scripts for core operation of the model, for building a global, monthly long‐term average dataset with all necessary environmental inputs, for computing physical properties of air, and for running the model with the global climate database. Example applications are provided in the paper and in the associated vignettes, including customisation the model to run with user‐supplied weather inputs.
A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice
Authors: Steurer Michael , Quittet Philippe , Papadaki Helen A. , Selleslag Dominik , Viallard Jean‐François , Kaiafa Georgia , Janssens Ann , Kozak Tomas , Wadenvik Hans , Schoonen Marieke , Belton Laura , Kreuzbauer Georg
Published: August 2016

Objective

Romiplostim has maintained long‐term platelet counts in patients with immune thrombocytopenia (ITP) for up to 5 yr in clinical studies. This prospective observational study aimed to describe romiplostim utilisation and outcomes in European clinical practice.

Methods

Adults with primary ITP who received romiplostim in routine care were eligible.

Results

Three‐hundred and forty patients were eligible for analysis, of whom 299 (88%) completed the 2‐yr observation period. The median age was 62 yr, with 43% of patients aged ≥65 yr, and two‐thirds of patients initiated romiplostim before splenectomy. The median average weekly dose of romiplostim was 2.8 μg/kg. The median baseline platelet count was 20 × 109/L, which increased after 2 wk of romiplostim treatment and remained >50 × 109/L thereafter. After romiplostim initiation, there was a decrease in rates of grade ≥3 bleeding events (from 12 to 2 per 100 patient‐years) and ITP‐related hospitalisations (from 87 to 33 per 100 patient‐years). The rate of thrombotic events was 2 per 100 patient‐years, and bone marrow fibrosis occurred in two patients.

Conclusions

Romiplostim dosing, effectiveness and safety in an unselected real‐world ITP population seemed comparable with that observed in clinical studies.
Extractability of Pb in urban gardens and orchards linked to soil properties
Authors: McBride M. B.
Published: August 2016

The hypothesis that lability and bioavailability of lead (Pb) in strongly contaminated soil is limited by interaction with phosphate and organic matter was tested on soil from urban gardens and orchards by extracting available Pb and P with the modified Morgan's extractant (ammonium acetate, pH 4.8) and measuring organic matter by loss‐on‐ignition. The extractable fraction of total Pb was larger in general in the urban garden than orchard soil, which indicates greater lability in urban garden soil than was expected if insoluble Pb phosphates such as pyromorphite were limiting Pb extractability. The extractable Pb fraction was generally larger in soil with greater total Pb, an indication that soil with large Pb concentrations contained Pb in more labile forms than soil with small concentrations. Larger organic matter contents in garden soil reduced the extractable fraction of Pb, but large available phosphate concentrations did not have this effect. The results indicate that soil organic matter has an important role in limiting Pb extractability in strongly contaminated soil, whereas a large soil phosphate concentration does not, despite the expectation that formation of insoluble Pb phosphates would reduce Pb lability. Nevertheless, a spatial association of P with Pb in Pb‐rich particles identified in urban garden soil with the electron microprobe suggests that Pb phosphates have formed in such soil from more reactive forms of Pb. The hypothesis is that a small fraction only of the total Pb in the urban soil occurs in a phosphate phase, and more acid‐labile forms of Pb co‐exist with insoluble phosphates for long time periods.

Highlights

Lead bioavailability in soil can potentially be reduced with phosphate.

Hypothesis is that soil Pb availability is limited by available phosphate or total organic matter.

Large soil organic matter content correlated with reduced Pb extractability, but not large available phosphorus content.

Lead‐phosphate phases did not appear to limit soil Pb extractability.
A Study of Logistics Networks: The Value of a Qualitative Approach
Authors: Houé Thierry , Murphy Eileen
Published: August 2016

The purpose of this paper is to demonstrate the relevance of a qualitative approach to map the nature and operation of the plural relationships of different logistics networks. Based on a literature review and an empirical study, a theoretical model of three logistics networks of proximity is presented, explained and linked to a discussion on the appropriateness of qualitative research in supply chain management. A matrix analysis is employed to develop the model. The paper confirms the significance of a qualitative view for the research considered. The advantages and limitations of such an approach are also examined. Finally, the paper provides new perspectives for research and supports the idea of an adaptation or a combination of methods in the field of supply chain management while refuting a methodological dogmatism.
Modeled ecohydrological responses to climate change at seven small watersheds in the northeastern United States
Authors: Pourmokhtarian Afshin , Driscoll Charles T. , Campbell John L. , Hayhoe Katharine , Stoner Anne M. K. , Adams Mary Beth , Burns Douglas , Fernandez Ivan , Mitchell Myron J. , Shanley James B.
Published: August 2016

A cross‐site analysis was conducted on seven diverse, forested watersheds in the northeastern United States to evaluate hydrological responses (evapotranspiration, soil moisture, seasonal and annual streamflow, and water stress) to projections of future climate. We used output from four atmosphere–ocean general circulation models (AOGCMs; CCSM4, HadGEM2‐CC, MIROC5, and MRI‐CGCM3) included in Phase 5 of the Coupled Model Intercomparison Project, coupled with two Representative Concentration Pathways (RCP 8.5 and 4.5). The coarse resolution AOGCMs outputs were statistically downscaled using an asynchronous regional regression model to provide finer resolution future climate projections as inputs to the deterministic dynamic ecosystem model PnET‐BGC. Simulation results indicated that projected warmer temperatures and longer growing seasons in the northeastern United States are anticipated to increase evapotranspiration across all sites, although invoking CO2 effects on vegetation (growth enhancement and increases in water use efficiency (WUE)) diminish this response. The model showed enhanced evapotranspiration resulted in drier growing season conditions across all sites and all scenarios in the future. Spruce‐fir conifer forests have a lower optimum temperature for photosynthesis, making them more susceptible to temperature stress than more tolerant hardwood species, potentially giving hardwoods a competitive advantage in the future. However, some hardwood forests are projected to experience seasonal water stress, despite anticipated increases in precipitation, due to the higher temperatures, earlier loss of snow packs, longer growing seasons, and associated water deficits. Considering future CO2 effects on WUE in the model alleviated water stress across all sites. Modeled streamflow responses were highly variable, with some sites showing significant increases in annual water yield, while others showed decreases. This variability in streamflow responses poses a challenge to water resource management in the northeastern United States. Our analyses suggest that dominant vegetation type and soil type are important attributes in determining future hydrological responses to climate change.
The Formation and Impact of Isomorphic Pressures: Extravagant Position‐Related Consumption in China
Authors: Gong Ting , Xiao Hanyu
Published: August 2016

In this article, we examine the impact of isomorphic pressures on institutional practices, a field that has not been adequately explored and explained. A critical issue, on which this article focuses, is the process by which isomorphic pressures translate into homogenous institutional practices across organizations. Drawing on the case of extravagant position‐related consumption in local governments in China, we identify the sources of isomorphic pressures, how they come to have an impact, in what ways they are manifested and how they are sustained. We find that institutionalized isomorphic pressures may create informal institutional practices in contradiction to formal legal norms. We further analyze the endogenous dynamics behind the formation of isomorphic pressures, which are deeply embedded in the complex web of Chinese bureaucratic relationships. This article is based on 65 in‐depth interviews with government officials as well as relevant government documents and media accounts.
Comparative virulence of in vitro‐cultured primate‐ and pig‐associated Helicobacter suis strains in a BALB/c mouse and a Mongolian gerbil model
Authors: Bosschem Iris , Flahou Bram , Bakker Jaco , Heuvelman Edwin , Langermans Jan A.M. , De Bruyne Ellen , Joosten Myrthe , Smet Annemieke , Ducatelle Richard , Haesebrouck Freddy
Published: August 2016

Background

Helicobacter suis (H. suis) is the most prevalent gastric non‐H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of nonhuman primates. The aim of this study was to obtain better insights into potential differences between pig‐ and primate‐associated H. suis strains in virulence and pathogenesis.

Materials and Methods

In vitro‐isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis), and rhesus monkeys (Macaca mulatta) were used for intragastric inoculation of BALB/c mice and Mongolian gerbils. Nine weeks and six months later, samples of the stomach of inoculated and control animals were taken for PCR analysis and histopathological examination.

Results

The cynomolgus monkey‐associated H. suis strain only colonized the stomach of mice, but not of Mongolian gerbils. All other H. suis strains colonized the stomach in both rodent models. In all colonized animals, severe gastric inflammation was induced. Gastric lymphoid follicles and destruction of the antral epithelium were observed in infected gerbils, but not in mice. Infection with both pig‐ and primate‐associated H. suis strains evoked a similar marked Th17 response in mice and gerbils, accompanied by increased CXCL‐13 expression levels.

Conclusions

Apart from the cynomolgus monkey‐associated strain which was unable of colonizing the stomach of Mongolian gerbils, no substantial differences in virulence were found in rodent models between in vitro‐cultured pig‐associated, cynomolgus monkey‐associated and rhesus monkey‐associated H. suis strains. The experimental host determines the outcome of the immune response against H. suis infection, rather than the original host.
Prognostic value of the albumin–bilirubin grade in patients with hepatocellular carcinoma: Validation in a Chinese cohort
Authors: Li Mu‐xing , Zhao Hong , Bi Xin‐yu , Li Zhi‐yu , Huang Zhen , Han Yue , Zhou Jian‐guo , Zhao Jian‐jun , Zhang Ye‐fan , Cai Jian‐qiang
Published: August 2016

Aim

The prognostic value of the newly raised objective liver function assessment tool, the albumin–bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child–Pugh (C‐P) score in predicting prognosis in this study.

Methods

The clinical data of 491 C‐P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C‐P score in predicting the short‐ and long‐term clinical outcomes were compared.

Results

The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C‐P score. With a median follow‐up of 57 months, the 1‐year, 3‐year, and 5‐year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C‐P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test.

Conclusions

The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C‐P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well‐designed studies with larger sample sizes are warranted.
Translation and evaluation of Chinese version of the symptom experience index
Authors: Li Kun , Fu Mei Rosemary , Zhao Qiheng , Chen Li
Published: August 2016

Symptom assessment is crucial for patient care through the entire disease trajectory. Patients often experience multiple symptoms concurrently. The symptom experience index is reliable and valid as an instrument developed in the USA for assessing multiple symptoms and distress. The aim of the study was to translate and evaluate the Chinese version of the instrument in healthy adults and oncology patients. This is a psychometric study with a cross‐sectional design. To ensure the semantic equivalence and content validity, an integrative translation method was employed to translate the English version into Chinese language. The participants were recruited during 2014 from a large university, two university‐affiliated hospitals and a community in Changchun, China. The Chinese version demonstrated high internal consistency, test–retest reliability and content validity. Construct validity was supported by factor analysis and significant differences of symptom experience scores between healthy and oncology groups. Participants' acceptance of the Chinese version and its ability to collect adequate data among Chinese population provided evidence for using this version among Chinese population. This study provided initial evidence to support the psychometric properties of the Chinese version. The Chinese version demonstrated adequate reliability and validity to assess multiple symptom experience by Chinese populations.
Sociodemographic associations of 4‐year overweight and obese incidence among a racially diverse cohort of healthy weight 18‐year‐olds
Authors: Young D. R. , Koebnick C. , Hsu J. ‐W. Y.
Published: August 2016

Background

Emerging adulthood is a critical time for excess weight gain. Risk can be masked if recommended overweight and obesity cut‐points for Asians are not employed.

Objectives

To determine the associations among sociodemographic factors and occurrence of overweight and obesity among normal weight 18‐year olds.

Methods

Normal weight (body mass index < 25 kg m−2; <23 kg m−2 for Asians) 18‐year‐old (9037 boys, 13 786 girls, 36% Hispanic, 34% non‐Hispanic Whites, 10% Black, 5% Asian) members of a healthcare organization in 2008 were followed through 2012 to identify incidence of overweight and obesity. Hazard ratios (HR) and 95% confidence intervals (CI) were determined controlling for sex, race/ethnicity, neighbourhood education, neighbourhood income and smoking status.

Results

After 3 years of follow‐up, the HR for overweight was 1.28 (95% CI: 1.12, 1.45) in the lowest quartile of neighbourhood education compared with the highest. Asians and Pacific Islanders had greater risk of overweight (HR 2.89, 95% CI: 2.55, 3.28; HR 3.13, 95% CI 2.23, 4.38) than non‐Hispanic Whites. Girls and Blacks were more likely to become obese than boys and non‐Hispanic Whites, as were those living in the lowest neighbourhood education quartile and lower neighbourhood income quartiles.

Conclusions

Girls, Asians, Blacks and those living in low education and income neighbourhoods during adolescence are at risk for excessive weight gain trajectories.
Chloride flux in phagocytes
Authors: Wang Guoshun
Published: August 2016

Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)–H2O2–halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium‐lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes.
Neutral serine proteases of neutrophils
Authors: Kettritz Ralph
Published: August 2016

Neutrophil serine proteases (NSPs) exercise tissue‐degrading and microbial‐killing effects. The spectrum of NSP‐mediated functions grows continuously, not least because of methodological progress. Sensitive and specific FRET substrates were developed to study the proteolytic activity of each NSP member. Advanced biochemical methods are beginning to characterize common and specific NSP substrates. The resulting novel information indicates that NSPs contribute not only to genuine inflammatory neutrophil functions but also to autoimmunity, metabolic conditions, and cancer. Tight regulatory mechanisms control the proteolytic potential of NSPs. However, not all NSP functions depend on their enzymatic activity. Proteinase‐3 (PR3) is somewhat unique among the NSPs for PR3 functions as an autoantigen. Patients with small‐vessel vasculitis develop autoantibodies to PR3 that bind their target antigens on the neutrophil surface and trigger neutrophil activation. These activated cells subsequently contribute to vascular necrosis with life‐threatening multiorgan failure. This article discusses various aspects of NSP biology and highlights translational aspects with strong clinical implications.
Neutrophils in cancer
Authors: Treffers Louise W. , Hiemstra Ida H. , Kuijpers Taco W. , van den Berg Timo K. , Matlung Hanke L.
Published: August 2016

Neutrophils play an important role in cancer. This does not only relate to the well‐established prognostic value of the presence of neutrophils, either in the blood or in tumor tissue, in the context of cancer progression or for the monitoring of therapy, but also to their active role in the progression of cancer. In the current review, we describe what is known in general about the role of neutrophils in cancer. What is emerging is a complex, rather heterogeneous picture with both pro‐ and anti‐tumorigenic roles, which apparently differs with cancer type and disease stage. Furthermore, we will discuss the well‐known role of neutrophils as myeloid‐derived suppressor cells (MDSC), and also on the role of neutrophils as important effector cells during antibody therapy in cancer. It is clear that neutrophils contribute substantially to cancer progression in multiple ways, and this includes both direct effects on the cancer cells and indirect effect on the tumor microenvironment. While in many cases neutrophils have been shown to promote tumor progression, for instance by acting as MDSC, there are also protective effects, particularly when antibody immunotherapy is performed. A better understanding of the role of neutrophils is likely to provide opportunities for immunomodulation and for improving the treatment of cancer patients.
Multifaceted effects of Francisella tularensis on human neutrophil function and lifespan
Authors: Kinkead Lauren C. , Allen Lee‐Ann H.
Published: August 2016

Francisella tularensis in an intracellular bacterial pathogen that causes a potentially lethal disease called tularemia. Studies performed nearly 100 years ago revealed that neutrophil accumulation in infected tissues correlates directly with the extent of necrotic damage during F. tularensis infection. However, the dynamics and details of bacteria–neutrophil interactions have only recently been studied in detail. Herein, we review current understanding regarding the mechanisms that recruit neutrophils to F. tularensis–infected lungs, opsonization and phagocytosis, evasion and inhibition of neutrophil defense mechanisms, as well as the ability of F. tularensis to prolong neutrophil lifespan. In addition, we discuss distinctive features of the bacterium, including its ability to act at a distance to alter overall neutrophil responsiveness to exogenous stimuli, and the evidence which suggests that macrophages and neutrophils play distinct roles in tularemia pathogenesis, such that macrophages are major vehicles for intracellular growth and dissemination, whereas neutrophils drive tissue destruction by dysregulation of the inflammatory response.
Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation
Authors: Ramadass Mahalakshmi , Catz Sergio D
Published: August 2016

Neutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed effector molecules stored in a variety of intracellular granules. Neutrophil granules contain microbicidal factors, the membrane‐bound components of the respiratory burst oxidase, membrane‐bound adhesion molecules, and receptors that facilitate the execution of all neutrophil functions including adhesion, transmigration, phagocytosis, degranulation, and neutrophil extracellular trap formation. The rapid mobilization of intracellular organelles is regulated by vesicular trafficking mechanisms controlled by effector molecules that include small GTPases and their interacting proteins. In this review, we focus on recent discoveries of mechanistic processes that are at center stage of the regulation of neutrophil function, highlighting the discrete and selective pathways controlled by trafficking modulators. In particular, we describe novel pathways controlled by the Rab27a effectors JFC1 and Munc13‐4 in the regulation of degranulation, reactive oxygen species and neutrophil extracellular trap production, and endolysosomal signaling. Finally, we discuss the importance of understanding these molecular mechanisms in order to design novel approaches to modulate neutrophil‐mediated inflammatory processes in a targeted fashion.
Tyrosine kinase signaling pathways in neutrophils
Authors: Futosi Krisztina , Mócsai Attila
Published: August 2016

Neutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation‐induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell‐surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes. In particular, Src‐family and Syk tyrosine kinases couple Fc‐receptors and adhesion receptors (integrins and selectins) to various neutrophil effector functions. This pathway shows surprising similarity to lymphocyte antigen receptor signaling and involves various other enzymes (e.g. PLCγ2), exchange factors (e.g. Vav‐family members) and adapter proteins (such as ITAM‐containing adapters, SLP‐76, and CARD9). Those mediators trigger various antimicrobial functions and play a critical role in coordinating the inflammatory response through the release of inflammatory mediators, such as chemokines and LTB4. Interestingly, however, tyrosine kinases have a limited direct role in the migration of neutrophils to the site of inflammation. Here, we review the role of tyrosine kinase signaling pathways in neutrophils and how those pathways contribute to neutrophil activation in health and disease.
Neutrophils and the inflammatory tissue microenvironment in the mucosa
Authors: Campbell Eric L. , Kao Daniel J. , Colgan Sean P.
Published: August 2016

The interaction of neutrophils (PMNs) and epithelial cells are requisite lines of communication during mucosal inflammatory responses. Consequences of such interactions often determine endpoint organ function, and for this reason, much interest has developed around defining the constituents of the tissue microenvironment of inflammatory lesions. Physiologic in vitro and in vivo models have aided in the discovery of components that define the basic inflammatory machinery that mold the inflammatory tissue microenvironment. Here, we will review the recent literature related to the contribution of PMNs to molding of the tissue microenvironment, with an emphasis on the gastrointestinal (GI) tract. We focus on endogenous pathways for promoting tissue homeostasis and the molecular determinants of neutrophil–epithelial cell interactions during ongoing inflammation. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.
The European Parliament's Diplomacy – a Tool for Projecting EU Power in Times of Crisis? The Case of the Cox–Kwasniewski Mission
Authors: Nitoiu Cristian , Sus Monika
Published: August 2016

The aim of this paper is to shed light on the way the European Parliament's diplomacy affects EU power, particularly during times of crisis. The analysis is focused on the Cox–Kwasniewski mission that the Parliament sent to Ukraine in 2012–13. Based on interviews and existing literature, we discuss the genesis and the development of the mission and then evaluate its impact. We argue that the mission with time became a key diplomatic instrument and enabled EU power projection by giving momentum to the promotion of the EU's approach towards Ukraine, which was already wavering due to the deadlock over the Association Agreement between Kyiv and Brussels and then due to President Yanukovych's refusal to sign the agreement.