bluuebunny/crossref_metadata_2025 huggingface dataset:
Whey Protein Lycosome Formulation Improves Vascular Functions and Plasma Lipids with Reduction of Markers of Inflammation and Oxidative Stress in Prehypertension
Authors: Petyaev Ivan M. , Dovgalevsky Pavel Y. , Klochkov Victor A. , Chalyk Natalya E. , Kyle Nigel
Published: December 2012

Parameters reflecting cardiovascular health and inflammation were studied in a pilot clinical trial conducted on 40 patients with prehypertension. The patients were treated with a new proprietary formulation of a whey protein (WP) isolate embedded into lycopene micelles (WPL) during a 1-month period. Control groups received lycopene or WP as a singular formulation or placebo pills for the same period of time. Combined WPL formulation of whey protein and lycopene has caused multiple favorable changes in the cardiovascular function (including a tendency to the reduced systemic blood pressure), the plasma lipid profile, and the inflammatory status of patients with prehypertension, whereas singular formulations of the compounds and placebo did not have such an effect. The reduction of plasma triglycerides and cholesterol fractions and almost two-fold decline in C-reactive protein (CRP) and inflammatory oxidative damage (IOD) levels as well as an increase in nitric oxide (NO), tissue oxygenation (StO2), and flow-mediated dilation values constitute the most significant benefit/outcome of the treatment with the combined formulation of whey protein and lycopene. The treatment did not affect the values of ankle-brachial index (ABI), body weight, and body mass index (BMI).
A Bat Algorithm with Mutation for UCAV Path Planning
Authors: Wang Gaige , Guo Lihong , Duan Hong , Liu Luo , Wang Heqi
Published: December 2012

Path planning for uninhabited combat air vehicle (UCAV) is a complicated high dimension optimization problem, which mainly centralizes on optimizing the flight route considering the different kinds of constrains under complicated battle field environments. Original bat algorithm (BA) is used to solve the UCAV path planning problem. Furthermore, a new bat algorithm with mutation (BAM) is proposed to solve the UCAV path planning problem, and a modification is applied to mutate between bats during the process of the new solutions updating. Then, the UCAV can find the safe path by connecting the chosen nodes of the coordinates while avoiding the threat areas and costing minimum fuel. This new approach can accelerate the global convergence speed while preserving the strong robustness of the basic BA. The realization procedure for original BA and this improved metaheuristic approach BAM is also presented. To prove the performance of this proposed metaheuristic method, BAM is compared with BA and other population-based optimization methods, such as ACO, BBO, DE, ES, GA, PBIL, PSO, and SGA. The experiment shows that the proposed approach is more effective and feasible in UCAV path planning than the other models.
Antimicrobial Activity and Phytochemical Screening ofBuchenavia tetraphylla(Aubl.) R. A. Howard (Combretaceae: Combretoideae)
Authors: de Oliveira Ygor Lucena Cabral , Nascimento da Silva Luís Cláudio , da Silva Alexandre Gomes , Macedo Alexandre José , Araújo Janete Magali de , Correia Maria Tereza dos Santos , Silva Márcia Vanusa da
Published: December 2012

This study evaluated the antimicrobial and hemolytic activities and phytochemical constituents of hydroalcoholic extract and its fractions fromBuchenavia tetraphyllaleaves. Cyclohexane (BTCF), ethyl acetate (BTEF), and n-butanol-soluble (BTSBF) and non-soluble (BTNBF) fractions were obtained from a liquid-liquid partition of hydroalcoholic extract (BTHE) fromB. tetraphyllaleaves. The hemolytic activity of active fractions was checked. The BTHE inhibited the growth ofMicrococcus luteus(MIC: 0.10 mg/mL),Pseudomonas aeruginosa(MIC: 0.20 mg/mL),Mycobacterium smegmatis(MIC: 0.39 mg/mL),Proteus vulgaris,andStaphylococcus aureus(MIC: 0.78 mg/mL for both). The more active fractions were BTCF and BTBSF. BTCF showed better potential to inhibitM. luteus(0.10 mg/mL),P. aeruginosa(0.20 mg/mL),S. enteritidis(0.39 mg/mL), andS. aureus(1.56 mg/mL). BTBSF showed the best results forM. luteus(0.10 mg/mL),M. smegmatis,B. subtilis(0.39 mg/mL for both), andP. vulgaris(0.10 mg/mL). The HC50 were greater than observed MIC: 20.30, 4.70 and 2.53 mg/mL, respectively, to BTBF, BTHE and BTCF, which. The phytochemical analysis detected the presence of flavanoids, triterpene, carbohydrate, and tannin. Our work showed for the first time the broad-spread antimicrobial activity ofB. tetraphylla, which has nonhemolytic action, creating a new perspective on the interesting association of traditional and scientific knowledge.
Chemical Composition and Fatty Acid Content of Some Spices and Herbs under Saudi Arabia Conditions
Authors: Al-Jasass Fahad Mohammed , Al-Jasser Mohammed Saud
Published: December 2012

Some Saudi herbs and spices were analyzed. The results indicated that mustard, black cumin, and cress seeds contain high amount of fat 38.45%, 31.95% and 23.19%, respectively, as compared to clove (16.63%), black pepper (5.34%) and fenugreek (4.51%) seeds. Cress, mustard, black cumin and black pepper contain higher protein contents ranging from 26.61 to 25.45%, as compared to fenugreek (12.91%) and clove (6.9%). Crude fiber and ash content ranged from 6.36 to 23.6% and from 3.57 to 7.1%, respectively. All seeds contain high levels of potassium (ranging from 383 to 823 mg/100g), followed by calcium (ranging from 75 to 270 mg/100g), Magnesium (ranged from 42 to 102 mg/100g) and iron (ranged from 20.5 to 65 mg/100g). However, zinc, manganese and copper were found at low levels. The major fatty acids in cress and mustard were linolenic acid (48.43%) and erucic acid (29.81%), respectively. The lenoleic acid was the major fatty acid in black cumin, fenugreek, black pepper and clove oils being 68.07%, 34.85%, 33.03% and 44.73%, respectively. Total unsaturated fatty acids were 83.24, 95.62, 86.46, 92.99, 81.34 and 87.82% for cress, mustard, black cumin, fenugreek, black pepper and clove, respectively. The differences in the results obtained are due to environmental factors, production areas, cultivars used to produce seeds and also due to the different methods used to prepare these local spices.
CHH islands: de novo DNA methylation in near-gene chromatin regulation in maize
Authors: Gent Jonathan I. , Ellis Nathanael A. , Guo Lin , Harkess Alex E. , Yao Yingyin , Zhang Xiaoyu , Dawe R. Kelly
Published: December 2012

Small RNA-mediated regulation of chromatin structure is an important means of suppressing unwanted genetic activity in diverse plants, fungi, and animals. In plants specifically, 24-nt siRNAs direct de novo methylation to repetitive DNA, both foreign and endogenous, in a process known as RNA-directed DNA methylation (RdDM). Many components of the de novo methylation machinery have been identified recently, including multiple RNA polymerases, but specific genetic features that trigger methylation remain poorly understood. By applying whole-genome bisulfite sequencing to maize, we found that transposons close to cellular genes (particularly within 1 kb of either a gene start or end) are strongly associated with de novo methylation, as evidenced both by 24-nt siRNAs and by methylation specifically in the CHH sequence context. In addition, we found that the major classes of transposons exhibited a gradient of CHH methylation determined by proximity to genes. Our results further indicate that intergenic chromatin in maize exists in two major forms that are distinguished based on proximity to genes—one form marked by dense CG and CHG methylation and lack of transcription, and one marked by CHH methylation and activity of multiple forms of RNA polymerase. The existence of the latter, which we call CHH islands, may have implications for how cellular gene expression could be coordinated with immediately adjacent transposon repression in a large genome with a complex organization of genes interspersed in a landscape of transposons.
Diagnostic value of serum concentrations of high‐mobility group‐box protein 1 and soluble hemoglobin scavenger receptor in brucellosis
Authors: Ayarcı Ayşe Oğuz , Yılmaz Emel , Sığırlı Deniz , Budak Ferah , Göral Güher , Oral Haluk Barbaros
Published: December 2012

Both cluster of differentiation (CD)4+ and CD8+ T lymphocytes play key roles in immunity to Brucella, in part because they secrete interferon (IFN)‐γ and activate bactericidal functions in macrophages. Therefore, use of markers of macrophage activation may have diagnostic and prognostic significance. High‐mobility group‐box 1 protein (HMGB1), a late‐onset pro‐inflammatory cytokine, is secreted by activated macrophages. Soluble hemoglobin scavenger receptor (sCD163) is a specific marker of anti‐inflammatory macrophages. The aim of this study was to investigate the diagnostic value of HMGB1 and sCD163 concentrations in brucellosis and its various clinical forms. Serum HMGB1 and sCD163 concentrations in 49 brucellosis patients were compared with those in 52 healthy control subjects. Both serum HMGB1 and sCD163 concentrations were significantly higher in brucellosis patients than in healthy controls (P < 0.001). There were no statistically significant differences in serum concentrations of HMGB1 and sCD163 between cases of acute, subacute and chronic brucellosis. Additionally, serum HMGB1 concentrations were positively correlated with sCD163 concentrations, whereas neither HMGB1 nor sCD163 concentrations were correlated with C‐reactive protein concentrations, white cell counts or erythrocyte sedimentation rates. Therefore, serum concentrations of HMGB1 and sCD163 may be diagnostic markers for brucellosis, but neither can be used to differentiate the three different forms of this disease (acute, subacute and chronic).
The relationship between carbon dioxide uptake and canopy colour from two camera systems in a deciduous forest in southern England
Authors: Mizunuma Toshie , Wilkinson Matthew , L. Eaton Edward , Mencuccini Maurizio , I. L. Morison James , Grace John
Published: December 2012

Carbon dioxide flux measurements using the eddy covariance (EC) methodology have helped researchers to develop models of ecosystem carbon balance. However, making reliable predictions of carbon fluxes is not straightforward due to phenological changes and possible abiotic/biotic stresses that profoundly influence tree functioning.

To assess the influence of canopy phenological state on CO2 flux, we installed two different digital camera systems at different viewing angles (an outdoor webcam with a near‐horizontal view and a commercial ‘fisheye’ digital camera with a downward view) on a flux measurement tower in southern England and tracked the visual change of the canopy in this oak‐dominated (Quercus robur L.) forest over two growing seasons.

Changes in the setting of the camera's white balance substantially affected the quality of the webcam images. However, the timing of the onset of greening and senescence was, nevertheless, detectable for the individual trees as well as the overall canopy for both years. The greening‐up date assessed from the downward images from a hemispherical lens was ∼5 days earlier than from the horizontal‐view images, because of ground vegetation development (not visible in the horizontal view).

The effects of a late air frost in 2010 were evident in the canopy greenness, and these led to reductions in daily gross primary productivity (GPP). The cameras recorded differences between individual tree crowns, showing their different responses to the late frost.

A major new finding from this work is the strong relationship between GPP and Hue, which was stronger than the relationship between GPP and NDVI.
Coombs’ Bastard Child: The Troubled Life of CDEP
Authors: Sanders Will
Published: December 2012

In the mid 1970s HC Coombs was a major promoter of the idea behind the CDEP scheme: that rather than pay lots of Aboriginal people in remote areas unemployment benefits it would be more constructive for them to be employed part‐time by local Indigenous organisations to undertake socially useful tasks. From this simple idea was born one of the most significant and, in time, one of the largest Indigenous‐specific programs Australia has seen, the Community Development Employment Projects scheme. The birth was not easy and neither has been the subsequent life of what I have called, with great licence, Coombs’ bastard child.
Collaborative Approaches to Regional Governance – Lessons from Victoria
Authors: Wear Andrew
Published: December 2012

Victoria's Regional Management Forums were established in 2005 to facilitate collaboration between Victorian Government departments and local government in each of Victoria's eight administrative regions. At the time they were established, Regional Management Forums were a pioneering experiment in collaborative governance. Seven years after their establishment, this paper examines the Regional Management Forums to consider how they have evolved, what role they now serve, and what lessons can be learned. This paper finds that Victoria's Regional Management Forums have been able to adapt to an evolving policy and governance context. While not without their challenges, Regional Management Forums have given rise to regional‐scale thinking and collaborative relationships.
Quantitative Assessment of the Sternal Rib End Morphology and Implications for Its Application in Aging Human Remains
Authors: Nikita Efthymia
Published: December 2012

Intercostal and age differences in the sternal rib end morphology of documented female skeletons fromSpitalfields andSt.Bride's are examined. The morphology was captured using three‐dimensional morphometrics and the statistical analyses employed included parametric and nonparametricMANOVA,discriminantanalysis, andmultilinearregressions. It was found that the quantified morphology of the sternal rib end was statistically significantly different between rib four and all other ribs except for the third one and that the morphological characteristics of all ribs varied with age. However, due to the inherent variability in sternal rib end morphology, nonstatistically significant results were obtained among the various age groups and neither disciminant nor multilinear regression analysis could be used for the estimation of the age of an individual based on digitized coordinates of the sternal rib end of individuals of known age, raising some concern as to the rigorousness of the fourth rib aging method.
Perceptions of fishers to sea turtle bycatch, illegal capture and consumption in the San Ignacio‐Navachiste‐Macapule lagoon complex, Gulf of California, Mexico
Authors: AGUILAR‐GONZÁLEZ Myrna E. , LUNA‐GONZÁLEZ Antonio , AGUIRRE Alonso , ZAVALA‐NORZAGARAY Alan A. , MUNDO‐OCAMPO Manuel , GONZÁLEZ‐OCAMPO Héctor A.
Published: December 2012

In this study, 10% of all registered fishermen in the coastal towns of Navachiste in Sinaloa, in northwestern Mexico, answered a survey designed to collect data on their perceptions of the following topics: the impact of turtle meat consumption; human health; bycatch; illegal turtle fishing; the illegal sea turtle market; the local economy; pollution; environmental education; the success of protective legislation; and sea turtle‐based ecotourism. Perceptions were analyzed using the fuzzy logic method through classification into 5 fuzzy membership sets: VL, very low; L, low; M, moderate; H, high; VH, very high. The 9 topics generated decision areas upon applying fuzzy inference that revealed the membership level of the answers in each fuzzy set. The economic potential of sea turtle‐based ecotourism and the economic profitability of the illegal turtle meat market were perceived as VL. Conservation legislation was perceived as H, although inefficiently applied due to corruption. Ecotourism and impacts on sea turtles were perceived as VL, because they were deemed unprofitable activities at the individual and community levels. Environmental education was perceived as L, because it centers on nesting, hatching and releasing turtles and is directed at elementary and middle‐school students. While fishers perceive a serious negative impact of fishing activities on sea turtles in the San Ignacio‐Navachiste‐Macapule area, they do not see themselves individually as part of the problem. Achieving sea turtle conservation in this region requires: suitable ecotourism infrastructure, government investments in promotion, and studies to estimate the minimum number of tourists needed to assure profitability.
Environmental ethics: an overview, assessing the place of bioscientists in society, supplemented with selected Australian perspectives
Authors: BUCKERIDGE John
Published: December 2012

Ethics deals with moral behavior in a professional context; ideally, it leads to a set of governing principles through which the appropriateness of any activity may be determined or assessed. Environmental ethics specifically deals with how humans interact with the biosphere. It is clear, however, that, as a species, we are failing in our duty of environmental stewardship. The encroachment of human activity into the natural environment is inexorable, and almost always deleterious. Any response to mitigate loss of taxa or ecosystems will have economic implications, and these are often considerable. In finding effective solutions, a process soon becomes political. In light of this we must reflect upon the leadership role that biologists have, especially our impact on policy development that pertains to natural resource management. Although our track record is no worse than any other professional group, biologists by way of training usually have a greater understanding of natural processes and must be prepared to articulate these publically. We have an ethical mandate to question decisions, policies and legislation that impact negatively upon biological systems: a mandate guided through logic, grounded in empirical science, and hopefully coupled with a deep understanding of the true value of both the living world and the physical world which sustains it. This paper uses Australian examples to demonstrate the frequent clashes between economics and biology, in anticipation that we should strive to achieve the underlying principles of sustainability, environmental stewardship and resource management in both daily decision‐making and in long‐term planning.
Size and dispersion of urticating setae in three species of processionary moths
Authors: PETRUCCO TOFFOLO Edoardo , ZOVI Daniel , PERIN Chiara , PAOLUCCI Paolo , ROQUES Alain , BATTISTI Andrea , HORVATH Helmuth
Published: December 2012

Larvae of the processionary moths of the Palaearctic region bear urticating setae that are released against vertebrate predators, especially insectivorous birds. A few species are pests of forest and urban trees and, consequently, may threaten human and animal health during outbreaks, causing dermatitis, conjunctivitis and respiratory distress. Although some studies provide detailed information about the setae, particularly those of the pine processionary moth Thaumetopoea pityocampa, there is little knowledge on the morphological traits of the setae and their release by the larvae. In the present study we identify major traits of the setae of 3 species of processionary moth, T. pityocampa, T. pinivora and T. processionea, which are potentially helpful in the understanding of setae dynamics in the environment: (i) diameter and length of setae and (ii) analysis of dynamical properties of the setae in the airborne state. Setae are highly variable in size, with bimodal distribution in T. pityocampa and T. pinivora; in these 2 species, short and long setae are interspersed within the integument fields where they occur. The difference in the seta size has important consequences in dispersion, as smaller setae can spread 5 times further than their bigger counterparts. This information is relevant for a full understanding of the defensive importance of larval setae against natural enemies of the processionary moths, as well for elucidating the importance of the processionary setae as air pollutants, both close to the infested trees and at longer distances.
Improving environmental and biodiversity monitoring in the Baltic Sea using DNA barcoding of Chironomidae (Diptera)
Authors: Brodin Y. , Ejdung G. , Strandberg J. , Lyrholm T.
Published: December 2012

As for many other regions, environmental and biodiversity monitoring of the brackish Baltic Sea suffers from low species resolution for several taxa. One such case is the benthic larvae of midges Chironomidae (Diptera), which are estimated to constitute about 30% of the macrozoobenthos species of the Baltic Sea and are important indicators of environmental quality. We assessed the usefulness of COI (cytochrome oxidase I) gene barcoding to improve species resolution and its potential for implementation in monitoring programmes. Neighbour‐Joining, Maximum parsimony and Bayesian‐inference analyses all provided high congruency with morphological analyses of adult males for almost all 42 species studied. Barcoding was helpful to elucidate some cases of taxonomical difficulties, such as synonyms. In contrast to the high identification accuracy when using our local database, there were a number of cases where matching with GenBank and BOLD provided puzzling results. For reliable species identification at least 15–30 specimens from 5–10 well‐distributed sites within the geographical range of the species might be needed in a database to adequately cover the intraspecific variability of chironomids. Implementation of DNA barcoding, as applied here, in monitoring would result in an increase from at present less than 10% to more than 90% successful chironomid species identification of Baltic Sea benthic samples, as it also would for many nearby lakes. Routine monitoring of benthic environmental samples based on Next‐Generation sequencing techniques would provide a cost effective way to obtain a taxonomically much more complete assessment of environmental quality and biodiversity, as required by EU directives and national legislation.
Hippocampal neurogenesis protects against cocaine‐primed relapse
Authors: Deschaux Olivier , Vendruscolo Leandro F. , Schlosburg Joel E. , Diaz‐Aguilar Luis , Yuan Clara J. , Sobieraj Jeffery C. , George Olivier , Koob George F. , Mandyam Chitra D.
Published: December 2012

Accumulating evidence demonstrates a functional role for the hippocampus in mediating relapse to cocaine‐seeking behavior and extinction‐induced inhibition of cocaine seeking, and dentate gyrus neurogenesis in the hippocampus may have a role. Here, we tested the hypothesis that disruption of normal hippocampal activity during extinction alters relapse to cocaine‐seeking behavior as a function of dentate gyrus neurogenesis. Adult rats were trained to self‐administer cocaine on a fixed‐ratio schedule, followed by extinction and cocaine‐primed reinstatement testing. Some rats received low‐frequency stimulation (LFS; 2 Hz for 25 minutes) after each extinction session in the dorsal or ventral hippocampal formation. All rats received an injection of the mitotic marker 5‐bromo‐2′‐deoxyuridine (BrdU) to label developing dentate gyrus neurons during self‐administration, as well as before or after extinction and LFS. We found that LFS during extinction did not alter extinction behavior but enhanced cocaine‐primed reinstatement. Cocaine self‐administration reduced levels of 24‐day‐old BrdU cells and dentate gyrus neurogenesis, which was normalized by extinction. LFS during extinction prevented extinction‐induced normalization of dentate gyrus neurogenesis and potentiated cocaine‐induced reinstatement of drug seeking. LFS inhibition of extinction‐induced neurogenesis was not due to enhanced cell death, revealed by quantification of activated caspase3‐labeled cells. These data suggest that LFS during extinction disrupts hippocampal networking by disrupting neurogenesis and also strengthens relapse‐like behaviors. Thus, newly born dentate gyrus neurons during withdrawal and extinction learning facilitate hippocampal networking that mediates extinction‐induced inhibition of cocaine seeking and may play a key role in preventing relapse.
High rates of midazolam injection and associated harms in Bangkok, Thailand
Authors: Hayashi Kanna , Suwannawong Paisan , Ti Lianping , Kaplan Karyn , Wood Evan , Kerr Thomas
Published: December 2012

Aims

To identify the prevalence and correlates of midazolam injection among injecting drug users in Thailand.

Design

Serial cross‐sectional mixed‐methods study.

Setting

Bangkok, Thailand.

Participants

  A total of 435 adults who had injected drug(s) in the past 6 months were recruited through peer outreach and word of mouth in Bangkok in 2011.

Measurements

Multivariable logistic regression was used to analyze self‐reported data collected through an interviewer‐administered survey in July–October 2011 (n = 435). Additionally, qualitative data were collected in June–July 2009 (n = 10) and analyzed to explore the health problems attributable to midazolam injection.

Findings

Among 435 survey participants, the prevalence of daily midazolam injection in the past 6 months was 37.0% (95% confidence interval: 32–42). While 75.8% of the daily midazolam injectors identified heroin as their drug of choice, 91.8% of these individuals reported substituting heroin with midazolam when heroin was unavailable. In multivariable analyses, daily midazolam injection was associated with femoral vein injection [adjusted odds ratio (AOR) = 4.48], polydrug use (AOR = 4.94), daily heroin injection (AOR = 3.25), binge use (AOR = 1.75) and perceived increase in policing pressure (AOR = 1.95) (all P < 0.05). Qualitative accounts indicated severe health problems associated with midazolam injection, including nerve and vascular injuries.

Conclusion

Midazolam misuse is increasing among injecting drug users in Bangkok and appears to be used primarily as a substitute for heroin. Midazolam injection was associated independently with various risk factors for injection‐related complications. Given the many deleterious effects of midazolam injection, novel interventions for midazolam injectors are needed urgently.
Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia
Authors: Kim Sun K. , Romero Roberto , Savasan Zeynep A. , Xu Yi , Dong Zhong , Lee Deug‐Chan , Yeo Lami , Hassan Sonia S. , Chaiworapongsa Tinnakorn
Published: December 2012

Objective

Cross‐talk between inflammation and angiogenesis pathways has been recently reported. The objectives of this study were to: (i) examine whether amniotic fluid (AF) concentrations of soluble endoglin (sEng), a protein with anti‐angiogenic properties, change during pregnancy, parturition, or intra‐amniotic infection and/or inflammation (IAI); (ii) determine whether an increase in sEng in the AF of patients with preterm labor (PTL) and preterm prelabor rupture of membranes (PROM) is associated with adverse neonatal outcomes; and (iii) investigate potential sources of sEng in AF.

Study design

A cross‐sectional study was conducted to include patients in the following groups: (i) mid‐trimester (n = 20); (ii) PTL with term delivery (n = 95); (iii) PTL leading to preterm delivery with (n = 40) and without IAI (n = 46); (iv) preterm PROM with (n = 37) and without IAI (n = 37); (v) term in labor (n = 48) and not in labor (n = 44). AF concentrations of sEng were determined by enzyme‐linked immunosorbent assay. Chorioamniotic membranes, umbilical cord blood, and AF macrophages were examined for the expression of endoglin.

Results

(i) Patients with IAI had a higher median AF concentration of sEng than those without IAI (P = 0.02 for PTL and 0.06 for preterm PROM); (ii) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI (OR 2.5 and 7.9, respectively); (iii) an AF sEng concentration ≥779.5 pg/mL was associated with bronchopulmonary dysplasia (BPD) (OR 7.9); (iv) endoglin was co‐localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and (v) the concentration of sEng in the supernatant was significantly increased after the treatment of macrophages with endotoxin or TNF‐α.

Conclusions

Soluble endoglin participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes.
Changes in the Fetal and Neonatal Cytokine Profile in Pregnancies Complicated by Fetal Growth Restriction
Authors: Mullins Edward , Prior Tomas , Roberts Irene , Kumar Sailesh
Published: December 2012

Fetal growth restriction (FGR) is a major complication of pregnancy with unknown etiology which results in marked fetal, neonatal and long‐term morbidity, and mortality. FGR is likely to result from suboptimal placental implantation and perturbed immunological interactions. The diagnostic criteria for FGR vary between studies and the condition often occurs with pre‐eclampsia. Here, we review published studies of fetal and neonatal cytokines in FGR and compare these with studies of small for gestational age, pre‐eclampsia and pregnancies delivering pre‐term.
Heterosexual Anal Intercourse: A Neglected Risk Factor for HIV?
Authors: Baggaley Rebecca F. , Dimitrov Dobromir , Owen Branwen N. , Pickles Michael , Butler Ailsa R. , Masse Ben , Boily Marie‐Claude
Published: December 2012

Heterosexual anal intercourse confers a much greater risk of HIV transmission than vaginal intercourse, yet its contribution to heterosexual HIV epidemics has been under researched. In this article we review the current state of knowledge of heterosexual anal intercourse practice worldwide and identify the information required to assess its role in HIV transmission within heterosexual populations, including input measures required to inform mathematical models. We then discuss the evidence relating anal intercourse and HIV with sexual violence.
In vivo Multiphoton Microscopy Technique to Reveal the Physiology of the Mouse Uterus
Authors: Zenclussen Ana C. , Olivieri David N. , Dustin Michael L. , Tadokoro Carlos E.
Published: December 2012

Problem

Pregnancy is a challenge to the maternal immune system as it allows the growing of a semiallogeneic fetus within the uterus. Such tolerance suggests a set of complex cellular distributions and interactions inside the organ. Until now, direct observation of such processes was absent because proper intravital imaging techniques were not available.

Method

We developed a new two‐photon microscope stage together with a set of surgical procedures to provide direct observation of immune cell within the mouse uterus.

Results

Using our technique, we observed an accumulation of dendritic cells (DCs) in the uterus during the estrus phase of the estrus cycle. Some of the observed DC clusters were located near the lumen of the uterus or small blood vessels, each situated on the antimesometrium side.

Conclusion

While two‐photon microscopy has become a widely used technology for intravital imaging, new advances in the development of staging and experimental protocols can still push the limits of this technique for exploring new biology. As proof of this, we demonstrated that with specially designed staging and surgical protocols, we observed the formation of DC clusters in the uterus; structures that may play a role in the complex immunology of the uterus–fetal interface.
Jihad as justification: National survey evidence of belief in violent jihad as a mediating factor for sacred violence amongMuslims inIndonesia
Authors: Muluk Hamdi , Sumaktoyo Nathanael G. , Ruth Dhyah Madya
Published: December 2012

Many factors have been used to explain sacred violence. Regardless of the abundance of theories, two issues have emerged: lack of national‐level evidence and lack of attention to the justification factor for the violence. We argue that belief in violent jihad serves as justification for sacred violence, and conducted two studies to address the issues. The first study provides narratives on violence justification. The second quantitatively tests the mediating role of belief in violent jihad on sacred violence. It was found that only violent jihad, but not religiosity, fundamentalism, support for Islamic law, or perceptions of unfairness predicted sacred violence.
Cesarean section en caul and asphyxia in preterm infants
Authors: Jin Zhen , Wang Xiaoyan , Xu Qiwei , Wang Pingting , Ai Wanting
Published: December 2012

We reviewed the outcome for 211 women undergoing a planned en caul (within intact membranes) cesarean section and for 836 control women with conventional lower segment section, in the period 2001–2010 at a university‐affiliated hospital in China, where the former technique has been practiced. Of the intended en caul sections there were 141 successful deliveries (66.8%), and 70 that failed and were converted to conventional lower segment cesarean section. Maternal blood loss was similar for both operation types, but the rate of asphyxia was significantly lower among preterm infants delivered by the en caul method than in the control cases. Multivariate logistic regression revealed that the volume of amniotic fluid, a low Bishop score and high birthweight were associated with failed en caul deliveries. Cesarean section en caul can be a safer option than lower segment section when preterm delivery is required.
Responsiveness of emergency obstetric care systems in low‐ and middle‐income countries: a critical review of the “third delay”
Authors: Cavallaro Francesca L. , Marchant Tanya J.
Published: December 2012

We reviewed the evidence on the duration, causes and effects of delays in providing emergency obstetric care to women attending health facilities (the third delay) in low‐ and middle‐income countries. We performed a critical literature review using terms related to obstetric care, birth outcome, delays and developing countries. A manual search of reference lists of key articles was also performed. 69 studies met the inclusion criteria. Most studies reported long delays in providing care, and the mean waiting time for women admitted with complications was as much as 24 h before treatment. The three most cited barriers to providing timely care were shortage of treatment materials, surgery facilities and qualified staff. Existing evidence is insufficient to estimate the effect of delays on birth outcomes. Delays in providing emergency obstetric care seem common in resource‐constrained settings but further research is necessary to determine the effect of the third delay on birth outcomes.
The impact of previous birth experiences on maternal fear of childbirth
Authors: Størksen Hege Therese , Garthus‐Niegel Susan , Vangen Siri , Eberhard‐Gran Malin
Published: December 2012

Objectives

This study aimed to assess the relation between fear of childbirth and previous birth experiences.

Design

A prospective study of pregnant women.

Setting

Akershus University Hospital, Norway.

Population

Parous women (n = 1357) scheduled to give birth at Akershus University Hospital in Norway during 2009–2011.

Methods

Data were collected using two self‐completed questionnaires at pregnancy weeks 17 and 32. Fear of childbirth was assessed by the Wijma Delivery Expectancy Questionnaire. Previous overall birth experience was measured using a numeric rating scale, and previous obstetric complications were assessed using an index of seven obstetric complications: emergency cesarean section, instrumental vaginal delivery, extensive blood loss, retained placenta, serious maternal infection during labor, thrombosis, and anal sphincter tears.

Main outcome measure

Fear of childbirth.

Results

The odds ratio of fear of childbirth was 4.8 (95% confidence interval (CI) 2.8–8.3) for a previous negative overall birth experience, 1.9 (95% CI 1.2–3.1) for one obstetric complication and 2.6 (95% CI 1.2–5.5) for two or more complications. The estimates were adjusted for mental health, labor pain, time since last delivery, age, and education. Almost 80% of women who experienced obstetric complications neither considered the birth a negative overall experience nor developed a fear of childbirth.

Conclusions

The association between a previous subjectively negative birth experience and fear of childbirth was high and was greater than the association between previous obstetric complications and fear of childbirth.
The Role of Self‐Concept in the Mechanism Linking Proactive Personality to Employee Work Outcomes
Authors: Liao Pen‐Yuan
Published: December 2012

This study uses cognitive consistency theory to develop a model linking proactive personality to employees' work outcomes. This model was tested using a sample of 161 subordinate–supervisor dyads. HLM analysis results revealed that organisation‐based self‐esteem fully mediated the relationships between proactive personality and the behaviors of job performance and organisational citizenship behavior‐voice and partially mediated the relationships between proactive personality and the attitudes of job satisfaction and affective organisational commitment. Furthermore, perceived insider status moderated the relationship between proactive personality and organisation‐based self‐esteem in such a way that the relationship was stronger for individuals lower rather than higher in perceived insider status.
Response to laboratory selection with cyromazine and susceptibility to alternative insecticides in sheep blowfly larvae from the New South Wales Monaro
Authors: Levot GW
Published: December 2012

Objective

To determine the significance of cyromazine resistance in blowfly larvae from a region where resistance has been previously confirmed and to measure susceptibility of the cyromazine‐resistant blowflies to ivermectin and spinosad.

Methods

Blowfly larvae from five properties located within 5 km of where cyromazine‐resistant Lucilia cuprina were detected in 2011 were tested for resistance to cyromazine. The original cyromazine‐resistant ‘Nimmitabel’ strain was reared for 13 generations on homogenised liver containing cyromazine at a concentration lethal to susceptible larvae. Larval development bioassays in which batches of neonate larvae were transferred onto homogenised bovine liver containing cyromazine or dicyclanil were used to determine whether the level of resistance had increased. The sensitivities of the ‘Nimmitabel’ strain to ivermectin and spinosad were also measured.

Results

Cyromazine‐resistant larvae were identified in samples from four of the five properties near to the site of the original resistance detection. The ‘Nimmitabel’ strain responded to laboratory selection by becoming more resistant to cyromazine (8×) and to dicyclanil (3×). No larvae died after feeding on homogenate containing cyromazine at a concentration lethal to susceptible larvae. There was no cross‐resistance to ivermectin or spinosad in the ‘Nimmitabel’ strain.

Conclusion

The modest increases in resistance to cyromazine and dicyclanil following laboratory selection suggest that unless the situation worsens considerably, it is unlikely that this resistance will have a significant effect on flystrike protection provided by these insecticides if applied as directed on product labels. Moreover, cyromazine‐resistant larvae remained susceptible to ivermectin and spinosad.
Early QT assessment – how can our confidence in the data be improved?
Authors: Darpo Borje , Garnett Christine
Published: December 2012

Exposure–response (ER) analysis has emerged as an important tool to interpret QT data from thorough QT (TQT) studies and allows the prediction of effects in the targeted patient population. Recently, ER analysis has also been applied to data from early clinical pharmacology studies, such as single and multiple ascending dose studies, in which high plasma concentrations are often achieved. In line with this, there is an on‐going discussion between sponsors, academicians and regulators on whether ‘early QT assessment’ can provide sufficiently high confidence in assessment of QT prolongation to replace the TQT study. In this article, we discuss how QT assessment can be applied to early clinical studies (‘early QT assessment’) and what we believe is needed to achieve the same high confidence in the data as we currently obtain from data from the TQT study. The power to exclude a QTc effect exceeding 10 ms in small sample sizes using ER analysis will be discussed and compared with time‐matched analysis, as described in the ICH E14 guidance. Two examples of early QT assessment are shared; one negative and one positive, and the challenge in terms of demonstrating assay sensitivity in the absence of a pharmacological positive control will be discussed. Finally, we describe a recent research proposal, which may generate data to support the replacement of the TQT study with data from QT assessment in early phase 1 studies.
A single intra‐articular injection with IL‐4 plus IL‐10 ameliorates blood‐induced cartilage degeneration in haemophilic mice
Authors: van Meegeren Monique E. R. , Roosendaal Goris , Coeleveld Katja , Nieuwenhuizen Laurens , Mastbergen Simon C. , Lafeber Floris P. J. G.
Published: December 2012

The combination of interleukin (IL)‐4 and IL‐10 protects against blood‐induced cartilage damage in vitro. It has been hypothesized that the combination of these cytokines is effective if applied early in the process of cartilage damage. The present study investigated whether a single intra‐articular injection of IL‐4 plus IL‐10 immediately after a joint bleed limits cartilage damage in an in vivo haemophilia mouse model of blood‐induced joint damage. Factor VIII knockout mice with severe haemophilia A were punctured once with a needle below the patella to induce a joint haemorrhage. Subsequently IL‐4 plus IL‐10 (n = 24) or vehicle (n = 24) was injected intra‐articularly. After 35 days, the time needed for development of detectable joint degeneration, knee joints were examined for cartilage damage by macroscopic and microscopic evaluation. A single intra‐articular injection of IL‐4 plus IL‐10 ameliorated progression of cartilage degeneration caused by a single joint bleed to a certain extent. No effect on inflammation was observed at this time point. A single intra‐articular injection of IL‐4 plus Il‐10 directly after a single joint bleed limits progression of cartilage degeneration over time. Improved bioavailability (half‐life) of both cytokines might improve their protective ability in the development of cartilage degeneration, and probably also inflammation.
Repeated short‐term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP)
Authors: Bussel James B. , Saleh Mansoor N. , Vasey Sandra Y. , Mayer Bhabita , Arning Michael , Stone Nicole L.
Published: December 2012

Eltrombopag is a thrombopoietin‐receptor agonist that stimulates platelet production and increases platelet counts in patients with chronic immune thrombocytopenia (ITP). This open‐label, single‐arm study evaluated consistency of response and safety following repeated intermittent dosing of eltrombopag 50 mg daily over 3 cycles (1 cycle = up to 6 weeks on therapy followed by up to 4 weeks off therapy). The primary endpoint was proportion of patients with a response (platelet count ≥50 × 109/l and ≥2× baseline) in Cycle 1 who subsequently responded in Cycle 2 or 3. Fifty‐two of 65 evaluable patients (80%) responded in Cycle 1; these responding patients comprised the primary analysis population. Of these, 45/52 (87%) responded in Cycle 2 or 3 [95% confidence interval (CI), 74–94%] and 34/48 (71%; 95% CI, 56–83%) responded in both Cycles 2 and 3. Time to response was consistent, with >50% of responders responding by Day 8 in each cycle. Bleeding rates relative to baseline decreased by approximately 50% during each treatment cycle. The frequency or severity of adverse events, most commonly headache, did not increase over successive cycles. If a chronic ITP patient not requiring consistent therapy responds to short‐term eltrombopag, then subsequent courses of eltrombopag, as needed, are likely to be safe and effective.
Gliotoxin is a potent NOTCH2 transactivation inhibitor and efficiently induces apoptosis in chronic lymphocytic leukaemia (CLL) cells
Authors: Hubmann Rainer , Hilgarth Martin , Schnabl Susanne , Ponath Elena , Reiter Marlies , Demirtas Dita , Sieghart Wolfgang , Valent Peter , Zielinski Christoph , Jäger Ulrich , Shehata Medhat
Published: December 2012

Chronic lymphocytic leukaemia (CLL) cells express constitutively activated NOTCH2 in a protein kinase C (PKC)– dependent manner. The transcriptional activity of NOTCH2 correlates not only with the expression of its target gene FCER2 (CD23) but is also functionally linked with CLL cell viability. In the majority of CLL cases, DNA‐bound NOTCH2 complexes are less sensitive to the γ‐secretase inhibitor (GSI) DAPT. Therefore, we searched for compounds that interfere with NOTCH2 signalling at the transcription factor level. Using electrophoretic mobility shift assays (EMSA), we identified the Aspergillum‐derived secondary metabolite gliotoxin as a potent NOTCH2 transactivation inhibitor. Gliotoxin completely blocked the formation of DNA‐bound NOTCH2 complexes in CLL cells independent of their sensitivity to DAPT. The inhibition of NOTCH2 signalling by gliotoxin was associated with down regulation of CD23 (FCER) expression and induction of apoptosis. Short time exposure of CLL cells indicated that the early apoptotic effect of gliotoxin is independent of proteasome regulated nuclear factor κB activity, and is associated with up regulation of NOTCH3 and NR4A1 expression. Gliotoxin could overcome the supportive effect of primary bone marrow stromal cells in an ex vivo CLL microenvironment model. In conclusion, we identified gliotoxin as a potent NOTCH2 inhibitor with a promising therapeutic potential in CLL.
BCR‐ABL1 transcript at 3 months predicts long‐term outcomes following second generation tyrosine kinase inhibitor therapy in the patients with chronic myeloid leukaemia in chronic phase who failed Imatinib
Authors: Kim Dennis D. , Lee Honggi , Kamel‐Reid Suzanne , Lipton Jeffrey H.
Published: December 2012

The BCR‐ABL1 transcript level at 3 months can predict long‐term outcomes following frontline therapy with Imatinib or Dasatinib in chronic myeloid leukaemia (CML) patients. However, data is lacking for second‐generation tyrosine kinase inhibitor (2GTKI) therapy after Imatinib failure. A total of 112 patients with CML in chronic phase receiving 2GTKI after Imatinib failure were reviewed. Treatment outcomes including complete cytogenetic (CCyR), major molecular (MMR) and molecular response 4·5 (4·5 log reduction of BCR‐ABL1 transcript level, MR4·5), treatment failure, progression‐free and overall survival (OS) were compared according to BCR‐ABL1 transcript levels at 3 or 6 months, divided into <1%IS, 1–10%IS and ≥10%IS. BCR‐ABL1 transcript level at 3 months showed better correlation with OS (P < 0·001) than that at 6 months (P = 0·147). Better OS was also observed in the patients achieving <1%IS (100%) and 1–10%IS (100%) than those with ≥10%IS at 3 months (70·6%, P < 0·001). Those with <1%IS showed the best CCyR, MMR and MR4·5 rates; 1–10%IS, intermediate; and ≥10%IS, the lowest CCyR, MMR and MR4·5 rates. The group with <1%IS at 3 months maintained significantly lower BCR‐ABL1 transcript level compared to other two groups. In conclusion, the BCR‐ABL1 transcript level at 3 months is the most relevant surrogate for outcomes following 2GTKI therapy after Imatinib failure.