bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of old, new and emerging medicines on metabolic aberrations in PCOS
Authors: Bargiota Alexandra , Diamanti-Kandarakis Evanthia
Published: March 2012

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age that is associated with significant adverse short- and long-term health consequences. Multiple metabolic aberrations, such as insulin resistance (IR) and hyperinsulinaemia, high incidence of impaired glucose tolerance, visceral obesity, inflammation and endothelial dysfunction, hypertension and dyslipidemia are associated with the syndrome. Assessing the metabolic aberrations and their long term health impact in women with PCOS is challenging and becomes more important as therapeutic interventions currently available for the management of PCOS are not fully able to deal with all these consequences. Current therapeutic management of PCOS has incorporated new treatments resulting from the better understanding of the pathophysiology of the syndrome. The aim of this review is to summarize the effect of old, new and emerging therapies used in the management of PCOS, on the metabolic aberrations of PCOS
Surface difference of novel fluorinated polyacrylate latex prepared with different surfactants
Authors: Chen L J , Wu F Q
Published: March 2012

The novel fluorinated polyacrylate latex was successfully prepared by emulsion polymerisation of perfluorononylene allyl ether (PFAE) with butyl acrylate (BA) and methyl methacrylate (MMA) initiated by potassium persulphate (KPS) in the water with different surfactants. PFAE was synthesised from the intermediate perfluoro nonene and 3-allyl alcohol as staring reactants. Films of the novel fluorinated polyacrylate latex were prepared by coating the latex directly on the clean glass sheet and allowed to dry at 80°C in a bake oven. The structure of the novel fluorinated polyacrylate latex was investigated by Fourier transform infrared spectrometry. Surface difference of novel fluorinated polyacrylate latex prepared with different surfactants was studied. Results show that the latex prepared with sodium dodecyl benzene sulphonate surfactant has smaller particle size, contact angle and lower surface tension. The latex prepared with sodium 2-hydroxy-3-(methacryloyloxy) propane-1-sulphonate surfactant has larger particle size, higher surface tension and larger contact angle.
Effect of pulse frequency on growth kinetics of ceramic coatings formed on 2090 Al–Li alloy
Authors: Zhao Z L , Chen L , Ren H G
Published: March 2012

Ceramic coatings of Al2O3 were prepared on a 2090 Al–Li alloy using a pulsating microarc oxidation (MAO) method in NaOH–Na2SiO3 aqueous solution. A two-stage regulating regime was used during the MAO process, initially at a constant current density of 5 A dm−2 and then at a constant voltage of 450 V. The effects of pulse frequency on coating growth kinetics, microstructure features and tensile properties were investigated. The growth rates of the coatings are enhanced with an increase in pulse frequency from 300 to 900 Hz at a constant current density. A high pulse frequency beyond 600 Hz significantly promotes nonlinear growth, which corresponds to the two-stage regulating regime. Owing to the influence of pulse frequency on coating growth rate and surface roughness, the tensile properties of a 2090 Al–Li alloy slightly decrease with increasing coating thickness. Thus, a high pulse frequency indirectly influences the tensile properties of a 2090 Al–Li alloy with ceramic coatings.
Surface processing of materials with fluorocarbon fed atmospheric pressure dielectric barrier discharges
Authors: Fanelli F
Published: March 2012

Nowadays, atmospheric pressure cold plasmas, particularly in dielectric barrier discharge (DBD) configuration, attract significant interest in the field of surface processing of materials. Fluorocarbon containing DBDs have also been studied, but the state of the art in this field is at its early stages, especially if compared to low pressure plasmas, which have been widely and successfully employed for the etching of inorganic and organic materials, for the deposition of fluoropolymers as well as for the treatment of synthetic and natural polymers. This contribution will provide an overview of our recent studies on fluorocarbon containing DBDs and will present results on the deposition of fluoropolymers concerning the tuning of the chemical composition of the deposits, the etching–deposition competition and the influence of feed gas contaminants (i.e. air and water vapour).
Growth and reactivity of Zn and ZnO on Pd(111)
Authors: Schennach R , Weber F , Piffl M , Weirum G , Surnev S
Published: March 2012

In this work, the adsorption and reactivity of Zn and ZnO on Pd(111) have been investigated using scanning tunnelling microscopy, temperature programmed desorption, density functional theory and reflection absorption infrared spectroscopy. Using this approach, it was shown that an ordered PdZn surface alloy already forms at room temperature. The electronic structure of this surface alloy resembles that of copper. Depending on the preparation method and temperature, different surface alloys and Zn layers can be formed. The ZnO growth on Pd(111) forms different ZnO structures. Both a (4×4) and a (6×6) structure are formed depending on the oxygen pressure during ZnO growth. The (4×4) structure is most likely a hydrogen terminated Zn6O5 structure. In an attempt to verify the hydrogen termination, this structure and the (6×6) structure, which corresponds to a graphite-like Zn6O6 structure, were investigated using reflection absorption infrared spectroscopy. The results show a vibrational feature that could correspond to the O–H stretch vibration of the hydrogen terminated structure.
Aging of surface properties of polyester fabrics treated with atmospheric pressure plasma for inkjet printing
Authors: Zhang C M , Fang K J
Published: March 2012

Aging of plasma surface modification of inkjet printing polyester fabric was investigated. Woven polyester fabrics were exposed to atmospheric pressure air plasma and then stored at the standard condition of 20°C and 65% relative humidity to perform the aging experiments. The surface morphology and chemical compositions of the control and treated samples were analysed by scanning electron microscopy and X-ray photoelectron spectroscopy. Wetting time was used to evaluate the surface hydrophilicity on each sample. The aging effect could be detected only in the surface chemical compositions, whereas the morphology remained stable for 45 days. Research on the antibleeding property and colour strength showed that the inkjet printing property of polyester fabrics decreased with increasing aging time until a plateau value was reached. The modified fabrics should be printed within 24 h after plasma treatment in order to get fresher colour and better antibleeding performance.
Corrosion study of new surface treatment/coating for AZ31B magnesium alloy
Authors: Song S , Shen W D , Liu M H , Song G-L
Published: March 2012

Different surface preparation processes and post-treatments were applied to ‘electroless’ E-coated AZ31B magnesium alloy. The corrosion performance of the differently treated samples was assessed by means of ASTM B117 salt spray, anodic polarisation curve and electrochemical impedance spectroscopy measurements respectively. The results show that the corrosion resistance of the ‘electroless’ E-coated AZ31B can be ranked in the following order: wet polishing+curing>dry polishing+curing≈wet polishing>dry polishing>commercial benchmark treatment. It suggests that a suitable pre- or post-treatment can significantly further improve the corrosion performance of an ‘electroless’ E-coated Mg alloy. The surfaces of the differently pre- and post-treated AZ31B were examined by SEM. It appears that the different corrosion resistances can be attributed to different microstructures of the surface films on AZ31B.
Characterisation of electroless nickel plated titanium powder
Authors: Zangeneh-Madar* K , Jafari A
Published: March 2012

In this study, pure titanium powder with an average size of 20 μm was treated by electroless nickel plating to obtain titanium–nickel composite/duplex powder. Two plating procedures were applied; continuous short period (CSP) and discontinuous long period (DLP) processes. The plated titanium powder particles as well as unplated ones were characterised by energy dispersive spectrometry (EDS), scanning electron microscopy (SEM), particle size analysis and X-ray mapping analysis methods. The nickel plated titanium powder was sprayed on the steel substrate by atmospheric plasma spray technique. Furthermore, the mixed titanium–nickel powder was also sprayed. The morphology of sprayed powders was compared with each other. It was found that nickel forms fine dispersed nodules on the surface of titanium powder particles in the CSP process, whereas it appeared as homogeneous layers on the surface of all the particles in the DLP process. Also, it was found that the mass deposited on the powder increased with the plating period. The sprayed nickel plated powder showed better microstructure than the sprayed nickel mixed one.
Microstructural, nanomechanical and antibacterial properties of magnetron sputtered nanocomposite thin films of CrN/Cu
Authors: Kuppusami P , Elangovan T , Murugesan S , Thirumurugesan R , Khan S , George R P , Ramaseshan R , Divakar R , Mohandas E , Mangalaraj D
Published: March 2012

Synthesis of nanocomposite thin films of CrN/Cu on (100) Si and titanium modified stainless steel (D-9 alloy) substrates by pulsed magnetron sputtering from a composite target of Cr–Cu using sputtering gas mixture of argon and nitrogen is investigated. X-ray diffraction analysis of the films deposited at 773 K and 10 sccm of nitrogen flowrate indicated that the films are nanocrystalline and biphasic (fcc CrN and fcc Cu). The films showed a peak hardness of ∼15 GPa and a Young's modulus of ∼200 GPa for those with a copper content of 15·1 at-%, and these values were found to decrease significantly with a Cu content of ⩾18·4 at-%. The evaluation of the antibacterial activity as a function of copper content in the range of 15·1–38·5 at-% indicated excellent antibacterial properties for CrN/Cu films with the copper content of 18·4 at-%. The phase stability of CrN of the nanocomposite is also discussed in relation to pure CrN thin films.
Tribological behaviour of nanostructured Al2O3 coatings
Authors: Singh V P , Sil A , Jayaganthan R
Published: March 2012

Nanostructured alumina coatings have been deposited on SS 304 substrate using atmospheric plasma spray process. In the present work, nanostructured feed powder is obtained by manual granulation of nano-Al2O3 powder particles followed by exhaustive sieving, which is helpful in their proper consolidation. The tribological performance of the nano-alumina coatings, such as dry sliding, slurry erosion and cavitation erosion, has been investigated and compared with conventional coatings. The superior wear and erosion resistance of nanostructured coatings as compared to conventional coatings are due to its higher hardness and effective hindrance to crack propagation. Wear mechanism was explained based on their microstructure and worn surface morphologies. The microhardness and porosity of the two coatings were also experimentally investigated.
Feasibility and kinetics of nitriding of pure titanium and Ti–6Al–4V in molten salt bath of potassium nitrate
Authors: Roy A , Shiva Kumar K , Raghunath A , Sharma R C , Shekhar R
Published: March 2012

Surface nitriding of pure Ti and Ti–6Al–4V alloy was performed in potassium nitrate molten salt bath at temperatures ranging from 600 to 700°C for 2–18 h. The formation of a compound nitride layer comprising of ϵ-Ti2N and δ-TiN phases was identified with thicknesses of 1–12 μm for pure Ti and 1–6 μm for Ti–6Al–4V respectively. Ti–6Al–4V was found to develop an oxide phase upon nitriding for >8 h at 700°C. Maximum hardness values of 1470 HV for pure Ti and 1367 HV for Ti–6Al–4V were achieved. Under identical treatment conditions, the pure Ti sample was found to produce a thicker nitride layer than that of Ti–6Al–4V, proving that the presence of alloying elements hinders the growth of the nitride layer. Our study concludes that the present salt bath nitriding technique can produce a comparatively thick case depth with reasonably high hardness at relatively low temperature.
Influence of incremental rate of anodising current on roughness and electrochemical corrosion of oxide film on titanium alloy Ti–10V–2Fe–3Al
Authors: Liu J H , Wu G L , Yu M , Wu L , Zhang Y , Li S M
Published: March 2012

In this study, the influence of incremental rate of anodising current VIR on the crystal structure, surface roughness and corrosion resistance of anodic oxide films on Ti–10V–2Fe–3Al was studied using Raman spectroscopy, atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarisation. The results showed that the surface roughness, crystal structure and electrochemical corrosion behaviour of anodic oxide films were remarkably affected by different VIR with regard to the change in the rate of anodising voltage. In addition, results of EIS and potentiodynamic polarisation revealed that the film that formed at VIR of 0··50 A min−1 had the highest corrosion resistance. Quantitative AFM characterisation showed good correlation between surface roughness and EIS results. Furthermore, results of Raman spectroscopy showed that the relative intensity of anatase and rutile had a tendency to increase with a decrease in VIR before reaching 0··50 A min−1.
Non-negative matrix factorisation methods for the spectral decomposition of MRS data from human brain tumours
Authors: Ortega-Martorell Sandra , Lisboa Paulo JG , Vellido Alfredo , Julià-Sapé Margarida , Arús Carles
Published: March 2012

Background

In-vivo single voxel proton magnetic resonance spectroscopy (SV 1H-MRS), coupled with supervised pattern recognition (PR) methods, has been widely used in clinical studies of discrimination of brain tumour types and follow-up of patients bearing abnormal brain masses. SV 1H-MRS provides useful biochemical information about the metabolic state of tumours and can be performed at short (< 45 ms) or long (> 45 ms) echo time (TE), each with particular advantages. Short-TE spectra are more adequate for detecting lipids, while the long-TE provides a much flatter signal baseline in between peaks but also negative signals for metabolites such as lactate. Both, lipids and lactate, are respectively indicative of specific metabolic processes taking place. Ideally, the information provided by both TE should be of use for clinical purposes. In this study, we characterise the performance of a range of Non-negative Matrix Factorisation (NMF) methods in two respects: first, to derive sources correlated with the mean spectra of known tissue types (tumours and normal tissue); second, taking the best performing NMF method for source separation, we compare its accuracy for class assignment when using the mixing matrix directly as a basis for classification, as against using the method for dimensionality reduction (DR). For this, we used SV 1H-MRS data with positive and negative peaks, from a widely tested SV 1H-MRS human brain tumour database.

Results

The results reported in this paper reveal the advantage of using a recently described variant of NMF, namely Convex-NMF, as an unsupervised method of source extraction from SV1H-MRS. Most of the sources extracted in our experiments closely correspond to the mean spectra of some of the analysed tumour types. This similarity allows accurate diagnostic predictions to be made both in fully unsupervised mode and using Convex-NMF as a DR step previous to standard supervised classification. The obtained results are comparable to, or more accurate than those obtained with supervised techniques.

Conclusions

The unsupervised properties of Convex-NMF place this approach one step ahead of classical label-requiring supervised methods for the discrimination of brain tumour types, as it accounts for their increasingly recognised molecular subtype heterogeneity. The application of Convex-NMF in computer assisted decision support systems is expected to facilitate further improvements in the uptake of MRS-derived information by clinicians.
A biochemical marker panel in MRI-proven hyperacute ischemic stroke-a prospective study
Authors: Knauer Carolin , Knauer Katharina , Müller Susanne , Ludolph Albert C , Bengel Dietmar , Müller Hans P , Huber Roman
Published: March 2012

Background

Computer tomography (CT) is still the fastest and most robust technique to rule out ICH in acute stroke. However CT-sensitivity for detection of ischemic stroke in the hyperacute phase is still relatively low. Moreover the validity of pure clinical judgment is diminished by several stroke imitating diseases (mimics). The "Triage® Stroke Panel", a biochemical multimarker assay, detects Brain Natriuretic Peptide (BNP), D-Dimers (DD), Matrix-Metalloproteinase-9 (MMP-9), and S100B protein and promptly generates a Multimarkerindex of these values (MMX). This index has been licensed for diagnostic purposes as it might increase the validity of the clinical diagnosis to differentiate between stroke imitating diseases and true ischemic strokes. Our aim was to prove whether the panel is a reliable indicating device for the diagnosis of ischemic stroke in a time window of 6 h to fasten the pre- and intrahospital pathway to fibrinolysis.

Methods

We investigated all consecutive patients admitted to our stroke unit during a time period of 5 months. Only patients with clinical investigation, blood sample collection and MRI within six hours from symptom onset were included. Values of biochemical markers were analyzed according to the results of diffusion weighted MR-imaging. In addition MMX-values in ischemic strokes were correlated with the TOAST-criteria. For statistical analysis the SAS Analyst software was used. Correlation coefficients were analyzed and comparison tests for two or more groups were performed. Statistical significance was assumed in case of p < 0.05. Finally a ROC-analysis was performed for the MMX-Index.

Results

In total 174 patients were included into this study (n = 100 strokes, n = 49 mimics, n = 25 transitoric ischemic attacks). In patients with ischemic strokes the mean NIHSS was 7.6 ± 6.2, while the mean DWI-lesion volume was 20.6 ml (range 186.9 to 4.2 ml). According to the MMX or the individual markers there was no statistically significant difference between the group of ischemic strokes and the group of mimics. Moreover the correlation of the index and the DWI-lesion-volume was poor (p = 0.2).

Conclusions

In our setting of acute MRI-proven ischemic stroke the used multimarker-assay (Triage® Stroke Panel) was not of diagnostic validity. We do not recommend to perform this assay as this might lead to a unjustified time delay.
Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families
Authors: Fernández-Rodríguez Juana , Quiles Francisco , Blanco Ignacio , Teulé Alex , Feliubadaló Lídia , Valle Jesús del , Salinas Mónica , Izquierdo Àngel , Darder Esther , Schindler Detlev , Capellá Gabriel , Brunet Joan , Lázaro Conxi , Pujana Miguel Angel
Published: March 2012

Background

Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results.

Methods

The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations.

Results

This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them.

Conclusions

Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.
TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients
Authors: Körner Christian , Riesner Katarina , Krämer Benjamin , Eisenhardt Marianne , Glässner Andreas , Wolter Franziska , Berg Thomas , Müller Tobias , Sauerbruch Tilman , Nattermann Jacob , Spengler Ulrich , Nischalke Hans Dieter
Published: March 2012

Background

Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC.

Methods

Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population.

Results

Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 106 IU/ml vs. 1.81 ± 0.23 × 106 IU/ml, p = 0.049).

Conclusions

The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.
Increasing organ donation via anticipated regret (INORDAR): protocol for a randomised controlled trial
Authors: O'Carroll Ronan E , Ferguson Eamonn , Hayes Peter C , Shepherd Lee
Published: March 2012

Background

Throughout the world there is an insufficient supply of donor organs to meet the demand for organ transplantations. This paper presents a protocol for a randomised controlled trial, testing whether a simple, theory-based anticipated regret manipulation leads to a significant increase in posthumous organ donor registrations.

Methods

We will use a between-groups, prospective randomised controlled design. A random sample of 14,520 members of the adult Scottish general public will be contacted via post. These participants will be randomly allocated into 1 of the 4 conditions. The no questionnaire control (NQC) group will simply receive a letter and donor registration form. The questionnaire control (QC) arm will receive a questionnaire measuring their emotions and non-cognitive affective attitudes towards organ donation. The theory of planned behavior (TPB) group will complete the emotions and affective attitudes questionnaire plus additional items assessing their cognitive attitudes towards organ donation, perceived control over registration and how they think significant others view this action. Finally, the anticipated regret (AR) group will complete the same indices as the TPB group, plus two additional anticipated regret items. These items will assess the extent to which the participant anticipates regret for not registering as an organ donor in the near future. The outcome variable will be NHS Blood and Transplant verified registrations as an organ donor within 6 months of receiving our postal intervention.

Discussion

This study will assess whether simply asking people to reflect on the extent to which they may anticipate regret for not registering as an organ donor increases organ donor registration 6 months later. If successful, this simple and easy to administer theory-based intervention has the potential to save lives and money for the NHS by reducing the number of people receiving treatments such as dialysis. This intervention may also be incorporated into future organ donor campaigns.

Trial registration number

ISRCTN: ISRCTN92204897
Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes
Authors: Chu Chih-Sheng , Lee Kun-Tai , Cheng Kai-Hong , Lee Min-Yi , Kuo Hsuan-Fu , Lin Tsung-Hsien , Su Ho-Ming , Voon Wen-Chol , Sheu Sheng-Hsiung , Lai Wen-Ter
Published: March 2012

Background

Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM).

Methods

Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT.

Results

Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine (1.01 versus 0.83 μ mol/l; P < 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic regression analysis.

Conclusions

These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.
Saharan dust and association between particulate matter and case-specific mortality: a case-crossover analysis in Madrid (Spain)
Authors: Díaz Julio , Tobías Aurelio , Linares Cristina
Published: March 2012

Background

Saharan dust intrusions are a common phenomenon in the Madrid atmosphere, leading induce exceedances of the 50 μg/m3- EU 24 h standard for PM10.

Methods

We investigated the effects of exposure to PM10 between January 2003 and December 2005 in Madrid (Spain) on daily case-specific mortality; changes of effects between Saharan and non-Saharan dust days were assessed using a time-stratified case-crossover design.

Results

Saharan dust affected 20% of days in the city of Madrid. Mean concentration of PM10 was higher during dust days (47.7 μg/m3) than non-dust days (31.4 μg/m3). The rise of mortality per 10 μg/m3 PM10 concentration were always largely for Saharan dust-days. When stratifying by season risks of PM10, at lag 1, during Saharan dust days were stronger for respiratory causes during cold season (IR% = 3.34% (95% CI: 0.36, 6.41) versus 2.87% (95% CI: 1.30, 4.47)) while for circulatory causes effects were stronger during warm season (IR% = 4.19% (95% CI: 1.34, 7.13) versus 2.65% (95% CI: 0.12, 5.23)). No effects were found for cerebrovascular causes.

Conclusions

We found evidence of strongest effects of particulate matter during Saharan dust days, providing a suggestion of effect modification, even though interaction terms were not statistically significant. Further investigation is needed to understand the mechanism by which Saharan dust increases mortality.
Superantigen profiles of emm and emm-like typeable and nontypeable pharyngeal streptococcal isolates of South India
Authors: Anand Thangarajan Durai , Rajesh Thangamani , Rajendhran Jeyaprakash , Gunasekaran Paramasamy
Published: March 2012

Background

The major virulence factors determining the pathogenicity of streptococcal strains include M protein encoded byemmandemm-like (emmL) genes and superantigens. In this study, the distribution ofemm, emmLand superantigen genes was analyzed among the streptococcal strains isolated from the patients of acute pharyngitis.

Methods

The streptococcal strains were isolated from the throat swabs of 1040 patients of acute pharyngitis. TheemmandemmLgenes were PCR amplified from each strain and sequenced to determine theemmtypes. The dot-blot hybridization was performed to confirm the pathogens as trueemmnontypeable strains. The presence of eleven currently known superantigens was determined in all the strains by multiplex PCR.

Results

Totally, 124 beta-hemolytic streptococcal strains were isolated and they were classified as group A streptococcus (GAS) [15.3% (19/124)], group C streptococcus (GCS) [59.7% (74/124)] and group G streptococcus (GGS) [25.0% (31/124)]. Among 124 strains, only 35 strains wereemmtypeable and the remaining 89 strains wereemmnontypeable. All GAS isolates were typeable, whereas most of the GCS and GGS strains were nontypeable. These nontypeable strains belong toS. anginosus[75.3% (67/89)] andS. dysgalactiaesubsp.equisimilis[24.7% (22/89)]. TheemmandemmLtypes identified in this study includeemm12.0(28.6%),stG643.0(28.6%),stC46.0(17.0%),emm30.11(8.5%),emm3.0(2.9%),emm48.0(5.7%),st3343.0(2.9%),emm107.0(2.9%) andstS104.2(2.9%). Various superantigen profiles were observed in typeable as well as nontypeable strains.

Conclusions

Multiplex PCR analysis revealed the presence of superantigens in all the typeable strains irrespective of theiremmtypes. However, the presence of superantigen genes inemmandemmLnontypeable strains has not been previously reported. In this study, presence of at least one or a combination of superantigen coding genes was identified in all theemmandemmLnontypeable strains. Thus, the superantigens may inevitably play an important role in the pathogenesis of these nontypeable strains in the absence of the primary virulence factor, M protein.
IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors
Authors: Regel Ivonne , Eichenmüller Melanie , Joppien Saskia , Liebl Johanna , Häberle Beate , Müller-Höcker Josef , Vollmar Angelika , von Schweinitz Dietrich , Kappler Roland
Published: March 2012

Background

Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and amplification of pleomorphic adenoma gene 1 (PLAG1) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers.

Results

The IGFBP3 gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of IGFBP3 in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced IGFBP3 expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells resulted in reduced colony formation, migration, and invasion.

Conclusion

This study provides the first direct evidence that the reactivation of IGFBP3 decreases aggressive properties of pediatric liver cancer cells and that IGFBP3 promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.
De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer
Authors: Wu Xiwei , Somlo George , Yu Yang , Palomares Melanie R , Li Arthur Xuejun , Zhou Weiying , Chow Amy , Yen Yun , Rossi John J , Gao Harry , Wang Jinhui , Yuan Yate-Ching , Frankel Paul , Li Sierra , Ashing-Giwa Kimlin Tam , Sun Guihua , Wang Yafan , Smith Robin , Robinson Kim , Ren Xiubao , Wang Shizhen Emily
Published: March 2012

Background

MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.

Methods

The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.

Results

More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.

Conclusions

Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.
Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy
Authors: Bowerman Melissa , Murray Lyndsay M , Boyer Justin G , Anderson Carrie L , Kothary Rashmi
Published: March 2012

Background

Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil.

Methods

Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at P < 0.05. For the remaining analyses, the Student's two-tail t test for paired variables and one-way analysis of variance (ANOVA) were used to test for differences between samples and data were considered significantly different at P < 0.05.

Results

Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific.

Conclusions

Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA and for other degenerative diseases characterized by muscular atrophy and postsynaptic immaturity.
Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges
Authors: Konold Timm , Bone Gemma E , Clifford Derek , Chaplin Melanie J , Cawthraw Saira , Stack Michael J , Simmons Marion M
Published: March 2012

Background

The majority of atypical bovine spongiform encephalopathy (BSE) cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes.

Results

Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry.

Conclusions

The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to the sampling regimes and methods that are currently in use.
NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C) stimulation
Authors: Lian Ling , Ciraci Ceren , Chang Guobin , Hu Jingdong , Lamont Susan J
Published: March 2012

Background

NLRC5 is a member of the CARD domain containing, nucleotide-binding oligomerization (NOD)-like receptor (NLR) family, which recognizes pathogen-associated molecular patterns (PAMPs) and initiates an innate immune response leading to inflammation and/or cell death. However, the specific role of NLRC5 as a modulator of the inflammatory immune response remains controversial. It has been reported to be a mediator of type I IFNs, NF-kB, and MHC class I gene. But no study on NLRC5 function has been reported to date in chickens. In the current study, we investigated the role of NLRC5 in the regulation of IFNA, IFNB, IL-6, and MHC class I in the chicken HD11 macrophage cell line, by using RNAi technology. HD11 cells were transfected with one of five siRNAs (s1, s2, s3, negative-siRNA, or a mixture of s1, s2, s3-siRNAs). After 24 hours, cells were exposed to LPS or poly (I:C) or a vehicle control. Gene expression of NLRC5, IFNA, IFNB, IL-6, and MHC class I at 2, 4, 6, and 8 hours post stimulation (hps) was quantified by qPCR.

Results

The expression of NLRC5, IFNA, IFNB, and IL-6 genes in negative irrelevant transfection controls was up-regulated at 2 hps after LPS treatment compared to the vehicle controls. S3-siRNA effectively knocked down NLRC5 expression at 4 hps, and the expression of IFNA and IFNB (but not IL-6 and MHC class I) was also down-regulated at 4 hps in s3-siRNA transfected cells, compared to negative irrelevant transfection controls. Stimulation by LPS appeared to relatively restore the decrease in NLRC5, IFNA, and IFNB expression, but the difference is not significant.

Conclusions

Functional characterization of chicken NLRC5 in an in vitro system demonstrated its importance in regulating intracellular molecules involved in inflammatory response. The knockdown of NLRC5 expression negatively mediates gene expression of IFNA and IFNB in the chicken HD11 cell line; therefore, NLRC5 likely has a role in positive regulation of IFNA and IFNB expression. No direct relationship was found between NLRC5 knockdown and IL-6 and MHC class I expression. Future studies will further clarify the roles of NLRC5 and other NLRs in infectious diseases of chickens and may increase the efficacy of antiviral vaccine design.
Random generation of RNA secondary structures according to native distributions
Authors: Nebel Markus E , Scheid Anika , Weinberg Frank
Published: March 2012

Background

Random biological sequences are a topic of great interest in genome analysis since, according to a powerful paradigm, they represent the background noise from which the actual biological information must differentiate. Accordingly, the generation of random sequences has been investigated for a long time. Similarly, random object of a more complicated structure like RNA molecules or proteins are of interest.

Results

In this article, we present a new general framework for deriving algorithms for the non-uniform random generation of combinatorial objects according to the encoding and probability distribution implied by a stochastic context-free grammar. Briefly, the framework extends on the well-known recursive method for (uniform) random generation and uses the popular framework of admissible specifications of combinatorial classes, introducing weighted combinatorial classes to allow for the non-uniform generation by means of unranking. This framework is used to derive an algorithm for the generation of RNA secondary structures of a given fixed size. We address the random generation of these structures according to a realistic distribution obtained from real-life data by using a very detailed context-free grammar (that models the class of RNA secondary structures by distinguishing between all known motifs in RNA structure). Compared to well-known sampling approaches used in several structure prediction tools (such as SFold) ours has two major advantages: Firstly, after a preprocessing step in time

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for the computation of all weighted class sizes needed, with our approach a set of m random secondary structures of a given structure size n can be computed in worst-case time complexity

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while other algorithms typically have a runtime in

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. Secondly, our approach works with integer arithmetic only which is faster and saves us from all the discomforting details of using floating point arithmetic with logarithmized probabilities.

Conclusion

A number of experimental results shows that our random generation method produces realistic output, at least with respect to the appearance of the different structural motifs. The algorithm is available as a webservice at http://wwwagak.cs.uni-kl.de/NonUniRandGen and can be used for generating random secondary structures of any specified RNA type. A link to download an implementation of our method (in Wolfram Mathematica) can be found there, too.
Helminth communities from two urban rat populations in Kuala Lumpur, Malaysia
Authors: Mohd Zain Siti N , Behnke Jerzy M , Lewis John W
Published: March 2012

Background

The prevalence of parasitic infections among commensal animals such as black and brown rats in many tropical countries is high and in comparison with studies on rodents in temperate climates, little is known about the community structure of their parasites. Rodent borne parasites pose threats to human health since people living in close proximity to rodent populations can be exposed to infection.

Methods

The helminth community structures of two urban rat populations in Kuala Lumpur, Malaysia were investigated. The rats were from two contrasting sites in the city caught over a period of 21 months in 2000-2002.

Results

Eleven species of helminth parasites comprising seven nematodes (Heterakis spumosum, Mastophorus muris, Nippostrongylus brasiliensis, Syphacia muris, Pterygodermatites tani/whartoni, Gongylonema neoplasticum, Angiostrongylus malaysiensis), three cestodes (Hymenolepis (Rodentolepis) nana, H. diminuta and Taenia taeniaeformis) and one acanthocephalan (Moniliformis moniliformis) were recovered from 346 Rattus rattus and 104 R. norvegicus from two urban sites, Bangsar and Chow Kit, during 2000-2002. Rattus rattus harboured over 60% of all helminths compared with R. norvegicus, although both host species played a dominant role in the different sites with, for example R. norvegicus at Bangsar and R. rattus at Chow Kit accounting for most of the nematodes. Overall 80% of rats carried at least one species of helminth, with the highest prevalences being shown by H. diminuta (35%), H. spumosum (29.8%) and H. nana (28.4%). Nevertheless, there were marked differences in prevalence rates between sites and hosts. The influence of extrinsic (year, season and site) and intrinsic (species, sex and age) factors affecting infracommunity structure (abundance and prevalence of infection) and measures of component community structure were analyzed.

Conclusions

Since at least two species of rat borne helminths in Kuala Lumpur have the potential to infect humans, and these showed high prevalences in the rats, the assessment and regular monitoring of infections carried by wild rodents have important roles to play in public health.