bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Effect of Two Driving Retraining Programs on On-Road Performance After Stroke
Authors: Devos Hannes , Akinwuntan Abiodun Emmanuel , Nieuwboer Alice , Tant Mark , Truijen Steven , De Wit Liesbet , Kiekens Carlotte , De Weerdt Willy
Published: April 2009

Background. Several driving retraining programs have been developed to improve driving skills after stroke. Those programs rely on different rehabilitation concepts. Objectives. The current study sought to examine the specific carryover effect of driving skills of a comprehensive training program in a driving simulator when compared with a cognitive training program. Methods. Further analysis from a previous randomized controlled trial that investigated the effect of simulator training on driving after stroke. Forty-two participants received simulator-based driving training, whereas 41 participants received cognitive training for 15 hours. Overall performance in the on-road test and each of its 13 items were compared between groups immediately posttraining and at 6 months poststroke. Results. Generalized estimating equation analysis showed that the total score on the on-road test and each item score improved significantly over time for both groups. Those who received driving simulator training achieved better results when compared with the cognitive training group in the overall on-road score and the items of anticipation and perception of signs, visual behavior and communication, quality of traffic participation, and turning left. Most of the differences in improvement between the 2 interventions were observed at 6 months poststroke. Conclusions . Contextual training in a driving simulator appeared to be superior to cognitive training to treat impaired on-road driving skills after stroke. The effects were primarily seen in visuointegrative driving skills. Our results favor the implementation of driving simulator therapy in the conventional rehabilitation program of subacute stroke patients with mild deficits.
Building Emotional Resilience to Promote Health
Authors: Davis Mary C.
Published: April 2009

In recent years, a growing body of evidence has linked positive emotional health with lower cardiovascular morbidity and mortality, independent of negative emotion. Several potential mechanisms have been posited to account for these associations, including improved health behavior, direct physiological benefits, and enhanced resistance to and recovery from stress among individuals with high versus low positive emotional resources. Links between positive emotion and health have implications for targeted interventions, but no empirical investigations to date have tested the impact of efforts to enhance positive emotion on cardiovascular risk. Nevertheless, some existing data point to the potential value of strategies to increase emotional resources for individuals' functional health and capacity to manage stress.
Understanding the seriousness of corporate crime
Authors: Almond Paul
Published: April 2009

The measurement of public attitudes towards the criminal law has become an important area of research in recent years because of the perceived desirability of ensuring that the legal system reflects broader societal values. In particular, studies into public perceptions of crime seriousness have attempted to measure the degree of concordance that exists between law and public opinion in the organization and enforcement of criminal offences. These understandings of perceived crime seriousness are particularly important in relation to high-profile issues where public confidence in the law is central to the legal agenda, such as the enforcement of work-related fatality cases. A need to respond to public concern over this issue was cited as a primary justification for the introduction of the Corporate Manslaughter and Corporate Homicide Act 2007. This article will suggest that, although literature looking at the perceived seriousness of corporate crime and, particularly, health and safety offences is limited in volume and generalist in scope, important lessons can be gleaned from existing literature, and pressing questions are raised that demand further empirical investigation.
Performance of neural networks in materials science
Authors: Bhadeshia H. K. D. H. , Dimitriu R. C. , Forsik S. , Pak J. H. , Ryu J. H.
Published: April 2009

Neural networks are now a prominent feature of materials science with rapid progress in all sectors of the subject. It is premature, however, to claim that the method is established. There are genuine difficulties caused by the often incomplete exploration and publication of models. The assessment presented here is an attempt to compile a loose set of guidelines for maximising the impact of any models that are created, in order to encourage thoroughness in publication to a point where the work can be independently verified.
Computational materials design and engineering
Authors: Kuehmann C. J. , Olson G. B.
Published: April 2009

Computational materials design integrates targeted materials process–structure and structure–property models in systems frameworks to meet specific engineering needs. Design inherently consists of many competing requirements that require judicious decisions regarding key tradeoffs. The goal of computational materials design is to apply the best scientific understanding to facilitate decisions regarding the optimal tradeoffs that meet desired needs in the most time and resource efficient manner. Mechanistic materials design models require adequate fidelity to determine the favourability of one design solution over another but also the ability to be extrapolated over large parameter space to search for design optima in unexplored terrain. Design processes must not only efficiently find optimal solutions, but quickly identify failures. More broadly, materials design can only be as successful as the ability to identify the correct requirements for an application, and those requirements must address not only performance but also qualification hurdles including prediction of manufacturing variation.
Superplastic forming of Zr based metallic glass ribbons under equibiaxial tension
Authors: Gong L. D. , Chan K. C. , Liu L. , Wang G.
Published: April 2009

In this paper, the superplastic forming behaviour of a Zr based metallic glass ribbon at different die diameters is examined. The wall thickness distribution and the relative bulging height values of the ribbon are experimentally determined, and the results are in reasonably good agreement with the finite element method (FEM) findings. The ribbon demonstrated early failure in both tensile tests and gas pressure forming. It is considered that the presence of air pockets in the as cast ribbon is one of the reasons for this. The FEM results also demonstrate that the air pockets may develop into localised regions which may eventually lead to failure of the ribbon. The differential scanning calorimeter curves of the as cast and deformed specimens show that the onset temperature of crystallisation is changed after deformation. This change is related to its change of microstructure. More work is needed to improve the formability of the ribbon and to study the post-deformed properties of the metallic glass.
Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia
Authors: Al-Saleh S. , Mei-Zahav M. , Faughnan M. E. , MacLusky I. B. , Carpenter S. , Letarte M. , Ratjen F.
Published: April 2009

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterised by vascular dysplasia complicated by visceral arteriovenous malformations (AVMs). To date, the diagnostic yield of screening procedures for pulmonary and cerebral AVMs in children with definite or potential HHT is not well defined. The aim of the present study was to prospectively evaluate the diagnostic yield of a screening protocol for pulmonary and cerebral AVMs in children with either a definite or potential HHT diagnosis.

All children referred for evaluation for HHT between 1996 and 2008 were included in the present analysis. Screening tests for AVMs included chest computed tomography and brain magnetic resonance imaging.

61 children with a definite clinical and/or genetic diagnosis of HHT were asymptomatic for visceral AVMs at their first baseline assessment (mean±sdage 8.7±4.7 yrs; range 0–17.0 yrs). Of these, 15 (25%) had pulmonary and/or cerebral AVMs diagnosed on initial screening tests. Pulmonary AVMs predominated in paediatric HHT patients (14 out of 15 patients) and were found in eight children aged <10 yrs. 55 children had a potential HHT diagnosis as they fulfilled only one or two HHT clinical diagnostic criteria and did not have a confirmatory genetic diagnosis (age 10.9±4.8 yrs; range 0–17.9 yrs). None of these children had pulmonary or cerebral AVMs on initial screening tests.

The present data suggest that children with a definite HHT diagnosis have a high frequency of pulmonary AVMs even when clinically asymptomatic. In contrast, no AVMs were observed in children not fulfilling HHT diagnostic criteria. Genetic testing appears to be useful in defining an at-risk group for pulmonary AVMs in childhood.
CTLA4gene polymorphisms are associated with chronic bronchitis
Authors: Zhu G. , Agusti A. , Gulsvik A. , Bakke P. , Coxson H. , Lomas D. A. , Silverman E. K. , Pillai S. G.
Published: April 2009

Chronic obstructive pulmonary disease (COPD) is characterised by chronic and progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell activation.

Genetic association between nineCTLA4single nucleotide polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896 individuals) from the International COPD Genetics Network (ICGN) population. We then replicated the associations in 342 COPD subjects with chronic bronchitis and 511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based association tests were used to analyse the ICGN cohort, and a logistic regression model was used for the Bergen cohort.

SixCTLA4SNPs were significantly associated with chronic bronchitis in the ICGN cohort (0.0079≤p≤0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325≤p≤0.0408). One of these replicated SNPs (rs231775) encodes the Thr to Ala substitution at amino acid position 17. Haplotype analyses supported the results of single SNP analyses.

Thus,CTLA4is likely to be a genetic determinant of chronic bronchitis among COPD cases.
CXCR3 ligands are augmented during the pathogenesis of pulmonary sarcoidosis
Authors: Busuttil A. , Weigt S. S. , Keane M. P. , Xue Y. Y. , Palchevskiy V. , Burdick M. D. , Huang C. , Zisman D. A. , Fishbein M. , Lynch J. P. , Strieter R. M. , Elashoff R. M. , Belperio J. A.
Published: April 2009

We and other investigators have hypothesised that the CXC chemokine receptor (CXCR)3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung granulomas; however, significant discrepancies in the current literature remain. In an effort to clarify previous conflicting findings, we performed the largest observational study to date of interferon-inducible ELR-(lacking the sequence glutamic acid–leucine–arginine) CXC chemokines in sarcoid bronchoalveolar fluid (BALF).

BALF chemokine levels from sarcoid patients (n = 72) and healthy controls (n = 8) were measured with the ELISA method. Immunohistochemical staining was performed for CXCR3 and its ligands.

BALF CXC chemokine ligand (CXCL)10 levels from sarcoid patients were not significantly increased compared with controls. BALF CXCL11 levels from sarcoid patients demonstrated a trend towards elevation; subgroup analysis by stage showed significant BALF CXCL11 elevation in stage I sarcoid patients compared with controls. BALF CXCL9 levels were elevated from sarcoid patients compared with controls. CXC11, CXCL9 and CXCR3 were expressed from epithelioid histiocytes, multinucleated giant cells and other inflammatory cells forming sarcoid lung granulomas.

Our data suggest that CXCL9 and CXCL11 are important mediators in recruiting CXCR3-expressing cells. Importantly, we have made the novel observation that both lymphocytes and cells of monocyte linage express CXCR3 and are involved in the formation of sarcoid lung granulomas.
Alveolar macrophages and CC chemokines are increased in children with cystic fibrosis
Authors: Brennan S. , Sly P. D. , Gangell C. L. , Sturges N. , Winfield K. , Wikstrom M. , Gard S. , Upham J. W.
Published: April 2009

Airway inflammation is an important component of cystic fibrosis (CF) lung disease. We sought to determine whether alveolar macrophages were involved in early CF lung disease.

Children with CF (median age 3.1 yrs) participated in a surveillance programme that included annual bronchoalveolar lavage (BAL). Control samples were obtained from non-CF children (median age 3.1 yrs; n = 24) investigated for persistent respiratory symptoms.

Pulmonary infection was detected in 31% (16 out of 51) and 38% (nine out of 24) of children from the CF and non-CF groups, respectively. Alveolar macrophages in BAL were increased in CF compared with non-CF in the absence of infection (223×103versus85×103 cells·mL−1; p = 0.001) and were associated with elevations in the CC chemokines (macrophage inflammatory protein (MIP)-3α (chemokine (C-C motif) ligand (CCL)20; 355.8versus46.0 pg·mL−1; p<0.001), monocyte chemotactic protein-1 (CCL2; 263.5versus25.3 pg·mL−1; p<0.001), MIP-1α (CCL3; 38.2versus4.9 pg·mL−1; p<0.001) and MIP-1β (CCL4; 326.6versus27.5 pg·mL−1; p<0.001)). Total cell counts and neutrophil numbers increased in the presence of infection; however, there was no additional effect of CF.

Alveolar macrophages and CC chemokines are elevated in the lungs in young children with CF even in the absence of pulmonary infection. Longitudinal studies are required to determine the clinical relevance of these findings.
Incidence and aetiology of eosinophilic pleural effusion
Authors: Krenke R. , Nasilowski J. , Korczynski P. , Gorska K. , Przybylowski T. , Chazan R. , Light R. W.
Published: April 2009

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia.

A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed.

We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (≤40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample.

Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.
Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis
Authors: Hussain Sajjad , Slevin Mark , Ahmed Nessar , West David , Choudhary Muhammad Iqbal , Naz Humera , Gaffney John
Published: April 2009

Background

Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with pathological processes, in particular tumour development, and is a target for the development of new therapies. We have investigated the anti-angiogenic potential of two naturally occurring stilbene glycosides (compounds 1 and 2) isolated from the medicinal plant Boswellia papyriferai using large and smallvessel-derived endothelial cells. Compound 1 (trans-4',5'-dihydroxy-3-methoxystilbene-5-O-{α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→6)}-β-D-glucopyranoside was the more hydrophilic and inhibited FGF-2-induced proliferation, wound healing, invasion in Matrigel, tube formation and angiogenesis in large and small vessel-derived endothelial cells and also in the chick chorioallantoic membrane assay. Using a binding assay we were able to show compound 1 reduced binding of FGF-2 to fibroblast growth factor receptors-1 and -2. In all cases the concentration of compound 1 which caused 50% inhibition (IC50) was determined. The effect of compound 1 on EGF and VEGF-induced proliferation was also investigated.

Results

Compound 1 inhibited all stages of FGF-2 induced angiogenesis with IC50 values in the range 5.8 ± 0.18 – 48.90 ± 0.40 μM but did not inhibit EGF or VEGF-induced angiogenesis. It also inhibited FGF-2 binding to FGF receptor-1 and -2 with IC50 values of 5.37 ± 1.04 and 9.32 ± 0.082 μM respectively and with concommotant down-regulation of phosphorylated-ERK-1/-2 expression. Compound 2 was an ineffective inhibitor of angiogenesis despite its structural homology to compound 1.

Conclusion

Compound 1 inhibited FGF-2 induced angiogenesis by binding to its cognate receptors and is an addition to the small number of natural product inhibitors of angiogenesis
Mitochondrial phylogeography of baboons (Papiospp.) – Indication for introgressive hybridization?
Authors: Zinner Dietmar , Groeneveld Linn F , Keller Christina , Roos Christian
Published: April 2009

Background

Baboons of the genusPapioare distributed over wide ranges of Africa and even colonized parts of the Arabian Peninsula. Traditionally, five phenotypically distinct species are recognized, but recent molecular studies were not able to resolve their phylogenetic relationships. Moreover, these studies revealed para- and polyphyletic (hereafter paraphyletic) mitochondrial clades for baboons from eastern Africa, and it was hypothesized that introgressive hybridization might have contributed substantially to their evolutionary history. To further elucidate the phylogenetic relationships among baboons, we extended earlier studies by analysing the complete mitochondrial cytochromebgene and the 'Brown region' from 67 specimens collected at 53 sites, which represent all species and which cover most of the baboons' range.

Results

Based on phylogenetic tree reconstructions seven well supported major haplogroups were detected, which reflect geographic populations and discordance between mitochondrial phylogeny and baboon morphology. Our divergence age estimates indicate an initial separation into southern and northern baboon clades 2.09 (1.54–2.71) million years ago (mya). We found deep divergences between haplogroups within several species (~2 mya, northern and southern yellow baboons, western and eastern olive baboons and northern and southern chacma baboons), but also recent divergence ages among species (< 0.7 mya, yellow, olive and hamadryas baboons in eastern Africa).

Conclusion

Our study confirms earlier findings for eastern Africa, but shows that baboon species from other parts of the continent are also mitochondrially paraphyletic. The phylogenetic patterns suggest a complex evolutionary history with multiple phases of isolation and reconnection of populations. Most likely all these biogeographic events were triggered by multiple cycles of expansion and retreat of savannah biomes during Pleistocene glacial and inter-glacial periods. During contact phases of populations reticulate events (i.e. introgressive hybridization) were highly likely, similar to ongoing hybridization, which is observed between East African baboon populations. Defining the extent of the introgressive hybridization will require further molecular studies that incorporate additional sampling sites and nuclear loci.
Use of the λ Red-recombineering method for genetic engineering of Pantoea ananatis
Authors: Katashkina Joanna I , Hara Yoshihiko , Golubeva Lyubov I , Andreeva Irina G , Kuvaeva Tatiana M , Mashko Sergey V
Published: April 2009

Background

Pantoea ananatis, a member of the Enterobacteriacea family, is a new and promising subject for biotechnological research. Over recent years, impressive progress in its application to L-glutamate production has been achieved. Nevertheless, genetic and biotechnological studies of Pantoea ananatis have been impeded because of the absence of genetic tools for rapid construction of direct mutations in this bacterium. The λ Red-recombineering technique previously developed in E. coli and used for gene inactivation in several other bacteria is a high-performance tool for rapid construction of precise genome modifications.

Results

In this study, the expression of λ Red genes in P. ananatis was found to be highly toxic. A screening was performed to select mutants of P. ananatis that were resistant to the toxic affects of λ Red. A mutant strain, SC17(0) was identified that grew well under conditions of simultaneous expression of λ gam, bet, and exo genes. Using this strain, procedures for fast introduction of multiple rearrangements to the Pantoea ananatis genome based on the λ Red-dependent integration of the PCR-generated DNA fragments with as short as 40 bp flanking homologies have been demonstrated.

Conclusion

The λ Red-recombineering technology was successfully used for rapid generation of chromosomal modifications in the specially selected P. ananatis recipient strain. The procedure of electro-transformation with chromosomal DNA has been developed for transfer of the marked mutation between different P. ananatis strains. Combination of these techniques with λ Int/Xis-dependent excision of selective markers significantly accelerates basic research and construction of producing strains.
Nanoparticle penetration and transport in living pumpkin plants: in situsubcellular identification
Authors: Corredor Eduardo , Testillano Pilar S , Coronado María-José , González-Melendi Pablo , Fernández-Pacheco Rodrigo , Marquina Clara , Ibarra M Ricardo , de la Fuente Jesús M , Rubiales Diego , Pérez-de-Luque Alejandro , Risueño María-Carmen
Published: April 2009

Background

In recent years, the application of nanotechnology in several fields of bioscience and biomedicine has been studied. The use of nanoparticles for the targeted delivery of substances has been given special attention and is of particular interest in the treatment of plant diseases. In this work both the penetration and the movement of iron-carbon nanoparticles in plant cells have been analyzed in living plants of Cucurbita pepo.

Results

The nanoparticles were applied in planta using two different application methods, injection and spraying, and magnets were used to retain the particles in movement in specific areas of the plant. The main experimental approach, using correlative light and electron microscopy provided evidence of intracellular localization of nanoparticles and their displacement from the application point. Long range movement of the particles through the plant body was also detected, particles having been found near the magnets used to immobilize and concentrate them. Furthermore, cell response to the nanoparticle presence was detected.

Conclusion

Nanoparticles were capable of penetrating living plant tissues and migrating to different regions of the plant, although movements over short distances seemed to be favoured. These findings show that the use of carbon coated magnetic particles for directed delivery of substances into plant cells is a feasible application.
A modified and automated version of the 'Fluorimetric Detection of Alkaline DNA Unwinding' method to quantify formation and repair of DNA strand breaks
Authors: Moreno-Villanueva María , Pfeiffer Ragen , Sindlinger Thilo , Leake Alan , Müller Marcus , Kirkwood Thomas BL , Bürkle Alexander
Published: April 2009

Background

Formation and repair of DNA single-strand breaks are important parameters in the assessment of DNA damage and repair occurring in live cells. The 'Fluorimetric Detection of Alkaline DNA Unwinding (FADU)' method [Birnboim HC, Jevcak JJ. Cancer Res (1981) 41:1889–1892] is a sensitive procedure to quantify DNA strand breaks, yet it is very tedious to perform.

Results

In order (i) to render the FADU assay more convenient and robust, (ii) to increase throughput, and (iii) to reduce the number of cells needed, we have established a modified assay version that is largely automated and is based on the use of a liquid handling device. The assay is operated in a 96-well format, thus greatly increasing throughput. The number of cells required has been reduced to less than 10,000 per data point. The threshold for detection of X-ray-induced DNA strand breaks is 0.13 Gy. The total assay time required for a typical experiment to assess DNA strand break repair is 4–5 hours.

Conclusion

We have established a robust and convenient method measuring of formation and repair of DNA single-strand breaks in live cells. While the sensitivity of our method is comparable to current assays, throughput is massively increased while operator time is decreased.
Effects and mechanisms of action of sildenafil citrate in human chorionic arteries
Authors: Maharaj Chrisen H , O'Toole Daniel , Lynch Tadhg , Carney John , Jarman James , Higgins Brendan D , Morrison John J , Laffey John G
Published: April 2009

Objectives

Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation.

Study Design

Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil.

Results

Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside.

Conclusion

Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.
Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis
Authors: Jeng Leo , Yamshchikov Alexandra V , Judd Suzanne E , Blumberg Henry M , Martin Gregory S , Ziegler Thomas R , Tangpricha Vin
Published: April 2009

Background

Vitamin D insufficiency is common in hospitalized patients. Recent evidence suggests that vitamin D may enhance the innate immune response by induction of cathelicidin (LL-37), an endogenous antimicrobial peptide produced by macrophages and neutrophils. Thus, the relationship between vitamin D status and LL-37 production may be of importance for host immunity, but little data is available on this subject, especially in the setting of human sepsis syndrome and other critical illness.

Methods

Plasma concentrations of 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (DBP) and LL-37 in critically ill adult subjects admitted to intensive care units (ICUs) with sepsis and without sepsis were compared to healthy controls.

Results

Critically ill subjects had significantly lower plasma 25(OH)D concentrations compared to healthy controls. Mean plasma LL-37 levels were significantly lower in critically ill subjects compared to healthy controls. Vitamin D binding protein levels in plasma were significantly lower in critically ill subjects with sepsis compared to critically ill subjects without sepsis. There was a significant positive association between circulating 25(OH)D and LL-37 levels.

Conclusion

This study demonstrates an association between critical illness and lower 25(OH)D and DBP levels in critically ill patients as compared to healthy controls. It also establishes a positive association between vitamin D status and plasma LL-37, which suggests that systemic LL-37 levels may be regulated by vitamin D status. Optimal vitamin D status may be important for innate immunity especially in the setting of sepsis. Further invention studies to examine this association are warranted.
Comparative study of the persistence of anti-HIV activity of deoxynucleoside HIV reverse transcriptase inhibitors after removal from culture
Authors: Paintsil Elijah , Grill Susan P , Dutschman Ginger E , Cheng Yung-Chi
Published: April 2009

Background

Most in vitro assays of drug potency may not adequately predict the performance in vivo. Methods to assess the persistence of antiviral activity of deoxynucleoside analogs, which require intracellular activation to the active metabolites that can persist in cells, will be important for designing dosages, combination regimens, and assessing treatment compliance. Using an HIV-IIIB/TZM-bl indicator cell culture system, we assessed the ability of an inhibitor to protect cells from infection and to delay viral rebound after removal of inhibitor from culture.

Results

The order of protection of cells from HIV-infection was 4'-Ed4T > LFD4C > DDI > D4T > 3TC > AZT > FTC > NVP. The fold-increase in EC50to delay viral rebound was DDI < 4'-Ed4T < LFD4C < FTC < D4T < 3TC < NVP < AZT. The ranking of persistence of anti-HIV activity of the inhibitors based on the two-component assay was DDI > 4'-Ed4T > LFD4C > FTC = D4T > 3TC > NVP > AZT.

Conclusion

The persistence ranking was derived from assays based on measures of single viral replication-cycle and cumulative inhibition at multiple time-points. Therefore, a better indicator of the pharmacodynamic property of an inhibitor. The persistence of anti-HIV activity assay may complement in vitro potency assays to better predict in vivo performance of nucleoside analogs.
Antidepressants Inhibit P2X4Receptor Function: a Possible Involvement in Neuropathic Pain Relief
Authors: Nagata Kenichiro , Imai Toshiyasu , Yamashita Tomohiro , Tsuda Makoto , Tozaki-Saitoh Hidetoshi , Inoue Kazuhide
Published: April 2009

Background

Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4receptors and analysed their analgesic mechanism using an animal model of neuropathic pain.

Results

Antidepressants strongly inhibited ATP-mediated Ca2+responses in P2X4receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4receptors, with IC50values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine.

Conclusion

These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part via their inhibitory effects on P2X4receptors.
On the performances of Intensity Modulated Protons, RapidArc and Helical Tomotherapy for selected paediatric cases
Authors: Fogliata Antonella , Yartsev Slav , Nicolini Giorgia , Clivio Alessandro , Vanetti Eugenio , Wyttenbach Rolf , Bauman Glenn , Cozzi Luca
Published: April 2009

Background

To evaluate the performance of three different advanced treatment techniques on a group of complex paediatric cancer cases.

Methods

CT images and volumes of interest of five patients were used to design plans for Helical Tomotherapy (HT), RapidArc (RA) and Intensity Modulated Proton therapy (IMP). The tumour types were: extraosseous, intrathoracic Ewing Sarcoma; mediastinal Rhabdomyosarcoma; metastastis of base of skull with bone, para-nasal and left eye infiltration from Nephroblastoma of right kidney; metastatic Rhabdomyosarcoma of the anus; Wilm's tumour of the left kidney with multiple liver metastases. Cases were selected for their complexity regardless the treatment intent and stage. Prescribed doses ranged from 18 to 53.2 Gy, with four cases planned using a Simultaneous Integrated Boost strategy. Results were analysed in terms of dose distributions and dose volume histograms.

Results

For all patients, IMP plans lead to superior sparing of organs at risk and normal healthy tissue, where in particular the integral dose is halved with respect to photon techniques. In terms of conformity and of spillage of high doses outside targets (external index (EI)), all three techniques were comparable; CI90% ranged from 1.0 to 2.3 and EI from 0 to 5%. Concerning target homogeneity, IMP showed a variance (D5%–D95%) measured on the inner target volume (highest dose prescription) ranging from 5.9 to 13.3%, RA from 5.3 to 11.8%, and HT from 4.0 to 12.2%. The range of minimum significant dose to the same target was: (72.2%, 89.9%) for IMP, (86.7%, 94.1%) for RA, and (79.4%, 94.8%) for HT. Similarly, for maximum significant doses: (103.8%, 109.4%) for IMP, (103.2%, 107.4%) for RA, and (102.4%, 117.2%) for HT. Treatment times (beam-on time) ranged from 123 to 129 s for RA and from 146 to 387 s for HT.

Conclusion

Five complex pediatric cases were selected as representative examples to compare three advanced radiation delivery techniques. While differences were noted in the metrics examined, all three techniques provided satisfactory conformal avoidance and conformation.
Development and evaluation of a tool for the assessment of footwear characteristics
Authors: Barton Christian J , Bonanno Daniel , Menz Hylton B
Published: April 2009

Background

Footwear characteristics have been linked to falls in older adults and children, and the development of many musculoskeletal conditions. Due to the relationship between footwear and pathology, health professionals have a responsibility to consider footwear characteristics in the etiology and treatment of various patient presentations. In order for health professionals and researchers to accurately and efficiently critique an individual's footwear, a valid and reliable footwear assessment tool is required. The aim of this study was to develop a simple, efficient, and reliable footwear assessment tool potentially suitable for use in a range of patient populations.

Methods

Consideration of previously published tools, other footwear related literature, and clinical considerations of three therapists were used to assist in the development of the tool. The tool was developed to cover fit, general features, general structure, motion control properties, cushioning, and wear patterns. A total of 15 participants (who provided two pairs of shoes each) were recruited, and assessment using the scale was completed on two separate occasions (separated by 1 – 3 weeks) by a physiotherapist and a podiatrist on each participant's dominant foot. Intra‐rater and inter‐rater reliability were evaluated using intra‐class correlation coefficients (ICCs) (model 2, 1) and the 95% limits of agreement (95% LOAs) for continuous items, and percentage agreement and kappa (κ) statistics for categorical items.

Results

All categorical items demonstrated high percentage agreement statistic for intra‐rater (83 – 100%) and inter‐rater (83 – 100%) comparisons. With the exception of last shape and objective measures used to categorise the adequacy of length, excellent intra‐rater (ICC = 0.91 – 1.00) and inter‐rater reliability (ICC = 0.90 – 1.00) was indicated for continuous items in the tool, including the motion control properties scale (0.91 – 0.95).

Conclusion

A comprehensive footwear assessment tool with good face validity has been developed to assist future research and clinical footwear assessment. Generally good reliability amongst all items indicates that the tool can be used with confidence in research and clinical settings. Further research is now required to determine the clinical validity of each item in various patient populations.
Mer tyrosine kinase (MerTK) promotes macrophage survival following exposure to oxidative stress
Authors: Anwar Adil , Keating Amy K , Joung David , Sather Susan , Kim Grace K , Sawczyn Kelly K , Brandão Luis , Henson Peter M , Graham Douglas K
Published: April 2009

Macrophages treated with hydrogen peroxide exhibit increased Mer-dependent signaling resulting in enhanced cellular survival in an oxidative stress environment.

The MerTK plays several important roles in normal macrophage physiology, including regulation of cytokine secretion and clearance of apoptotic cells. Mer signaling in other cell types, including malignant cells that ectopically overexpress the RTK, leads to downstream prosurvival pathway activation. We explored the hypothesis that Mer has a prosurvival role in macrophages exposed to oxidative stress. H2O2 treatment of peritoneal exudate murine macrophages and J774 cells rapidly stimulated Mer phosphorylation in a concentration-dependent manner. Mer phosphorylation was dependent on the ligand Gas6, as treatment with warfarin or MerFc (a fusion protein of the extracellular domain of Mer and the Fc portion of human Ig), inhibitors of Gas6 activity, blocked H2O2-mediated activation of Mer. Antiapoptotic signals including pAkt and pErk 1/2 were increased dramatically (threefold and 4.5-fold, respectively) in WT Mer-positive macrophages compared with Mer KO macrophages stimulated with H2O2. In a consistent manner, Mer expression led to decreased cleavage of proapoptotic indicators PARP and Caspase-3. Furthermore, Mer provided up to twofold enhanced cellular survival to primary macrophages exposed to H2O2. These data represent the first report of Mer activation in response to oxidative stress and demonstrate the ability of Mer RTK to promote macrophage survival in disease states that involve an oxidative stress environment.
IL-10 protects monocytes and macrophages from complement-mediated lysis
Authors: Koch Nadine , Jung Mechthild , Sabat Robert , Krätzschmar Jörn , Döcke Wolf-Dietrich , Asadullah Khusru , Volk Hans-Dieter , Grütz Gerald
Published: April 2009

A new function for IL-10 is shown which might enable IL-10-programmed macrophages to survive longer in hostile inflammatory environment.

Phagocytes, such as monocytes and macrophages, are important cells of the innate immunity in the defense against microbes. So far, it is unclear how these cells survive at the site of combat against microbes, where a hostile inflammatory environment prevails with strong complement activity. We hypothesized that IL-10, a key cytokine involved in the resolution of inflammation, induces resistance to complement attack. Here, we demonstrate for the first time such a cell-protective effect of IL-10 on human monocytes and macrophages. IL-10 is indeed able to protect these cell types in an in vitro model of complement lysis triggered by an anti-MHCI antibody or by binding of zymosan. Investigating potential underlying mechanisms, we found that IL-10 up-regulated the expression of complement regulatory membrane protein CD59 and the general cell-protective stress protein HO-1 in human monocytes. However, further functional analysis failed to link these individual IL-10-mediated effects with the increased protection from complement lysis. Blocking the protective effect of CD59 with an antibody increased complement lysis but did not abrogate the IL-10-protective effect. Interestingly, chemical interference with HO-1 activity did abrogate the protective effect of IL-10, but siRNA-mediated knockdown of HO-1 did not confirm this observation. Our results suggest that IL-10 generates pathogen-clearing phagocytes, which are resistant to complement lysis and thereby, enabled to survive longer in a hostile inflammatory environment.
Obliquity-correction imaging condition for reverse time migration
Authors: Costa J. C. , Silva Neto F. A. , Alcântara M. R. , Schleicher J. , Novais A.
Published: April 2009

The quality of seismic images obtained by reverse time migration (RTM) strongly depends on the imaging condition. We propose a new imaging condition that is motivated by stationary phase analysis of the classical crosscorrelation imaging condition. Its implementation requires the Poynting vector of the source and receiver wavefields at the imaging point. An obliquity correction is added to compensate for the reflector dip effect on amplitudes of RTM. Numerical experiments show that using an imaging condition with obliquity compensation improves reverse time migration by reducing backscattering artifacts and improving illumination compensation.
Hairy1 acts as a node downstream of Wnt signaling to maintain retinal stem cell-like progenitor cells in the chick ciliary marginal zone
Authors: Kubo Fumi , Nakagawa Shinichi
Published: April 2009

In the vertebrate retina, stem cell-like progenitor cells are maintained in a distinct region called the ciliary marginal zone (CMZ). Canonical Wnt signaling regulates the maintenance of the progenitor cells in the CMZ. However, its downstream molecular mechanisms have remained largely unclear. Here, we show that chick Hairy1, an established Notch signaling effector,mediates the Wnt-dependent maintenance of CMZ progenitor cells in chicken. Interestingly, unlike other developmental contexts in which Hes gene expression is regulated by Notch signaling, Hairy1 expression in the CMZ is regulated by Wnt signaling. Hairy1 is necessary and sufficient for the expression of a set of molecular markers characteristic of the CMZ, and Wnt2b fails to induce CMZ markers when Hairy1 activity is inhibited. Furthermore,microarray analysis identifies multiple Wnt-responsive transcription factors that activate Hairy1 expression. We thus propose that Hairy1 functions as a node downstream of Wnt signaling to maintain progenitor cells in the chick CMZ.
Effect of distance between 90° elbow close to upstream of orifice plate and the orifice plate on discharge coefficient
Authors: Yoon J Y , Sung N W , Lee C H
Published: April 2009

The effect of distance between 90° elbow close to the upstream face of an orifice plate and the orifice plate on discharge coefficient was investigated. The distribution of discharge coefficient and differential pressure caused by elbow and short upstream straight length were examined and a modified discharge coefficient was introduced. The results presented in this study could be useful when the orifice plate is installed under the condition of simple flow disturbance element and short upstream straight length.
Condition prediction based on wavelet packet transform and least squares support vector machine methods
Authors: Zhao F , Chen J , Xu W
Published: April 2009

Owing to the importance of condition maintenance, it is urgently required to predict condition in order to avoid unexpected failure. This article presents a new comprehensive prognostic approach for condition prediction based on wavelet packet transform and least squares support vector machine (LS-SVM). Comparision with traditional LS-SVM is also done to show its advantages. Simulation and experiment have been conducted to test the method. In the experiment, vibration data that were collected from the equipment is used to predict condition.
Salivary steroid assays – research or routine?
Authors: Wood Peter
Published: April 2009

Salivary concentrations of unconjugated steroids reflect those for free steroids in serum although concentrations may differ because of salivary gland metabolism. Samples for salivary steroid analysis are stable for up to 7 days at room temperature, one month or more at 4°C and three months or more at −20°C. When assessed against strict criteria, the evidence shows that salivary cortisol in evening samples or following dexamethasone suppression provides a reliable and effective screen for Cushing's syndrome. Sequential salivary cortisol measurements are also extremely helpful for the investigation of suspected cyclical Cushing's syndrome. There is potential for the identification of adrenal insufficiency when used with Synacthen stimulation. Salivary 17-hydroxyprogesterone and androstenedione assays are valued as non-invasive tests for the home-monitoring of hydrocortisone replacement therapy in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The diagnostic value of salivary oestradiol, progesterone, testosterone, dehydroepiandrosterone and aldosterone testing is compromised by rapid fluctuations in salivary concentrations of these steroids. Multiple samples are required to obtain reliable information, and at present the introduction of these assays into routine laboratory testing is not justified.