bluuebunny/crossref_metadata_2025 huggingface dataset:
The involvement of the RET variant G691S in medullary thyroid carcinoma enlightened by a meta‐analysis study
Authors: Lantieri Francesca , Caroli Francesco , Ceccherini Isabella , Griseri Paola
Published: November 2012

Medullary thyroid carcinoma (MTC) is a rare tumor, partially explained by mutations in the rearranged during transfection (RET) proto‐oncogene. The nonsynonymous RET polymorphism G691S has been reported as associated with MTC, but findings are discordant. We sought to clarify the role of G691S in MTCs through in silico analysis, genetic association in our patients and a meta‐analysis with extensive literature revision. Ninety‐three Italian patients were compared to 85 healthy individuals. Results were included in a meta‐analysis together with 11 case‐control association studies identified through PubMed, EMBASE and Web of Science, with a combined sample of 968 cases and 2,115 controls. No association of G691S with MTC was found in our sample; however, we observed an excess of homozygotes for the variant, significantly higher among females. The overall allelic association in the meta‐analysis was significant under the fixed‐effect model (odds ratio [OR] = 1.22 [95% confidence intervals: 1.06–1.39], p = 0.0049), but borderline under the random effect model (OR = 1.21 [0.99–1.46], p = 0.0575), with a moderate/high heterogeneity (I2 = 44.6%, p = 0.047). Under the recessive model of transmission, applied to the eight studies with available genotype frequencies, results were significant under both effect models (OR = 2.016 and OR = 2.022, p = 0.0004). No heterogeneity was anymore detectable. In silico analyses on G691S confirmed a change of the phosphorylation pattern that might account for the enhanced signaling transduction previously reported for G691S in several cancers, thus also explaining its overrepresentation in MTCs. The G691S variant allele does increase the risk for MTC, with a recessive mechanism of action, apparently more evident among females.
Restriction endonuclease‐mediated real‐time digestion‐PCR for somatic mutation detection
Authors: Zhao Jinyin , Xie Feifei , Zhong Wei , Wu Weili , Qu Shoufang , Gao Shangxian , Liu Licheng , Zhao Jing , Wang Mengzhao , Zhou Junyi , Jie Huang , Chen Weijun
Published: November 2012

PCR is a powerful platform for clinical and diagnostic applications, but challenges remain in detecting somatic mutations, as mutant cells are often mixed with more numerous wild‐type cells at the tissue‐sample sites. Here, we describe a novel method that couples PCR with restriction endonuclease digestion (designated real‐time digestion‐PCR, or RTD‐PCR) in a one‐step reaction tube for detecting somatic mutations from a minority of cells. The PCR mixture contains a thermostable restriction enzyme that digests wild‐type alleles during the PCR program, allowing selective amplification of the mutant alleles. To validate this method, we used real‐time digestion‐PCR for the specific detection of the EGFR (epidermal growth factor receptor) treatment resistance‐inducing mutation, T790M, combining with three different platforms: Sanger sequencing, TaqMan probe PCR and Sequenom MassArray. From 78 clinical samples, seven T790M mutations were consistently detected on all three platforms, indicating that RTD‐PCR may be a useful clinical tool for analyzing the T790M point mutation.
Circulating 25‐hydroxyvitamin D, vitamin D‐binding protein and risk of prostate cancer
Authors: Weinstein Stephanie J. , Mondul Alison M. , Kopp William , Rager Helen , Virtamo Jarmo , Albanes Demetrius
Published: November 2012

We recently reported a significant positive association between 25‐hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D‐binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and statistical tests were two sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR = 1.81, 95% CI: 1.18–2.79 for highest vs. lowest quintile, p‐trend = 0.001) compared to those with DBP below the median (OR = 1.22, 95% CI: 0.81–1.84, p‐trend 0.97; p‐interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR = 0.96, 95% CI: 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (<median) 25(OH)D concentrations (OR = 0.59, 95% CI: 0.38–0.90 for highest vs. lowest quintile, p‐trend = 0.003) and increased risk in men with higher 25(OH)D concentrations (OR = 1.47, 95% CI: 0.98–2.20, p‐trend 0.10, p‐interaction = 0.02). Our data suggest that the primary vitamin D carrier protein, DBP, modulates the impact of vitamin D status on prostate cancer.
Transcriptional and post‐transcriptional regulation of β‐secretase
Authors: Tamagno Elena , Guglielmotto M. , Monteleone D. , Vercelli A. , Tabaton M.
Published: November 2012

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that results in loss of memory and cognitive function, eventually leading to dementia. A key neuropathological event in AD is the cerebral accumulation of senile plaques formed by aggregates of amyloid‐β‐peptides (Aβ). Aβ results from two sequential endoproteolytic cleavages operated on the amyloid‐β precursor protein (AβPP), an integral membrane protein with a single‐membrane spanning domain, a large extracellular N‐terminus and a shorter, cytoplasmic C‐terminus. First, β‐secretase (BACE1) cleaves AβPP at the N‐terminal end of the Aβ sequence to produce a secreted form of AβPP, named sAβPP, and a C‐terminal membrane‐bound 99‐aminoacid fragment (C99). Then, γ‐secretase cleaves C99 within the transmembrane domain to release the Aβ peptides of different lengths, predominantly Aβ1‐40 and Aβ1‐42. © 2012 IUBMB IUBMB Life, 64(12): 943–950, 2012
Imaging of the DNA damage‐induced dynamics of nuclear proteins via nonlinear photoperturbation
Authors: Tomas Martin , Blumhardt Philipp , Deutzmann Anja , Schwarz Tobias , Kromm Dimitri , Leitenstorfer Alfred , Ferrando‐May Elisa
Published: November 2012

Understanding the cellular response to DNA strand breaks is crucial to decipher the mechanisms maintaining the integrity of our genome. We present a novel method to visualize how the mobility of nuclear proteins changes in response to localized DNA damage. DNA strand breaks are induced via nonlinear excitation with femtosecond laser pulses at λ = 1050 nm in a 3D‐confined subnuclear volume. After a time delay of choice, protein mobility within this volume is analysed by two‐photon photoactivation of PA‐GFP fusion proteins at λ = 775 nm. By changing the position of the photoactivation spot with respect to the zone of lesion the influence of chromatin structure and of the distance from damage are investigated. As first applications we demonstrate a locally confined, time‐dependent mobility increase of histone H1.2, and a progressive retardation of the DNA repair factor XRCC1 at damaged sites. This assay can be used to map the response of nuclear proteins to DNA damage in time and space. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Na+/H+‐exchanger (NHE1) generates pH nanodomains at focal adhesions
Authors: Ludwig Florian Timo , Schwab Albrecht , Stock Christian
Published: November 2012

Many tumor cells are characterized by an increased net acid production. They extrude the excess protons mainly through the Na+/H+‐exchanger NHE1. An increased NHE1 activity elevates the metastatic potential of tumor cells. Cell migration, a key step in the metastatic cascade, requires the formation and release of integrin‐mediated cell–matrix contacts (focal adhesions). As NHE1 has been localized to focal adhesion sites, the present study tests the hypothesis that NHE1 generates measurable pH nanodomains right at focal adhesions. In order to ratiometrically measure pH close to the plasma membrane, we established a novel application of the total internal reflection fluorescence microscopy (TIRFM). Human melanoma cells were transfected with DsRed2‐paxillin to identify focal adhesion sites. The pH‐sensitive dyes BCECF and WGA‐fluorescein were used to measure the submembranous cytosolic and the pericellular pH, respectively. Distinct pH nanodomains were found at focal adhesions, particularly at those located at the cell front, where NHE1 was concentrated. These sites featured a remarkably alkaline cytosolic and an acidic pericellular pH and thus a much steeper proton gradient across the plasma membrane compared to the rest of the cell. The generation of pH nanodomains could be assigned to NHE1‐mediated H+ export because such pH domains could not be detected in NHE1‐deficient cells. Given that both integrin avidity and mechanisms contributing to adhesion turnover are pH‐sensitive, we propose that pH nanodomains at focal adhesions, locally created and maintained by NHE1 activity especially at the cell front, modulate adhesion dynamics in migrating cells. J. Cell. Physiol. 228: 1351–1358, 2013. © 2012 Wiley Periodicals, Inc.
MirPlex: A Tool for Identifying miRNAs in High‐Throughput sRNA Datasets Without a Genome
Authors: Mapleson Daniel , Moxon Simon , Dalmay Tamas , Moulton Vincent
Published: November 2012

MicroRNAs (miRNAs) are a class of small non‐coding RNA (sRNA) involved in gene regulation through mRNA decay and translational repression. In animals, miRNAs have crucial regulatory functions during embryonic development and they have also been implicated in several diseases such as cancer, cardiovascular and neurodegenerative disorders. As such, it is of importance to successfully characterize new miRNAs in order to further study their function. Recent advances in sequencing technologies have made it possible to capture a high‐resolution snapshot of the complete sRNA content of an organism or tissue. A common approach to miRNA detection involves searching such data for telltale miRNA signatures. However, current miRNA prediction tools usually require a sequenced genome to analyse regions flanking aligned sRNA reads in order to identify characteristic miRNA hairpin secondary structures. Since only a handful of published genomes are available, there is a need for novel methods to identify miRNAs in sRNA datasets from high‐throughput sequencing devices without requiring a reference genome. This paper presents miRPlex, a tool for miRNA prediction that requires only sRNA datasets as input. Mature miRNAs are predicted from such datasets through a multi‐stage process, involving filtering, miRNA:miRNA* duplex generation and duplex classification using a support vector machine. Tests on sRNA datasets from model animals demonstrate that the tool is effective at predicting genuine miRNA duplexes, and, for some sets, achieves a high degree of precision when considering only the mature sequence. J. Exp. Zool. (Mol. Dev. Evol.) 320B:47–56, 2013. © 2012 Wiley Periodicals, Inc.
Moving beyond readmission penalties: Creating an ideal process to improve transitional care
Authors: Burke Robert E. , Kripalani Sunil , Vasilevskis Eduard E. , Schnipper Jeffrey L.
Published: November 2012

Hospital readmissions are common and costly; this has resulted in their emergence as a key quality indicator in the current era of renewed focus on cost containment. However, many concerns remain about the use of readmissions as a hospital quality measure and about how to reduce hospital readmissions. These concerns stem in part from deficiencies in the state of the science of transitional care. A conceptualization of the “ideal” discharge process could help address these deficiencies and move the state of the science forward. We describe an ideal transition in care, explicate the key components, discuss its implications in the context of recent efforts to reduce readmissions, and suggest next steps for policymakers, researchers, healthcare administrators, practitioners, and educators. Journal of Hospital Medicine 2013;8:102–109. © 2012 Society of Hospital Medicine
Impact of clinical history on chest radiograph interpretation
Authors: Test Matthew , Shah Samir S. , Monuteaux Michael , Ambroggio Lilliam , Lee Edward Y. , Markowitz Richard I. , Bixby Sarah , Diperna Stephanie , Servaes Sabah , Hellinger Jeffrey C. , Neuman Mark I.
Published: November 2012

BACKGROUND

The inclusion of clinical information may have unrecognized influence in the interpretation of diagnostic testing.

OBJECTIVE

The objective of the study was to determine the impact of clinical history on chest radiograph interpretation in the diagnosis of pneumonia.

DESIGN

Prospective case‐based study.

METHODS

Radiologists interpreted 110 radiographs of children evaluated for suspicion of pneumonia. Clinical information was withheld during the first interpretation. After 6 months the radiographs were reviewed with clinical information. Radiologists reported on pneumonia indicators described by the World Health Organization (ie, any infiltrate, alveolar infiltrate, interstitial infiltrate, air bronchograms, hilar adenopathy, pleural effusion).

SETTING

Children's Hospital of Philadelphia and Boston Children's Hospital.

PARTICIPANTS

Six board‐certified radiologists.

OUTCOME MEASURES

Inter‐ and inter‐rater reliability were assessed using the kappa statistic.

RESULTS

The addition of clinical history did not have a substantial impact on the inter‐rater reliability in the identification of any infiltrate, alveolar infiltrate, interstitial infiltrate, pleural effusion, or hilar adenopathy. Inter‐rater reliability in the identification of air bronchograms improved from fair (k = 0.32) to moderate (k = 0.53). Intra‐rater reliability for the identification of alveolar infiltrate remained substantial to almost perfect for all 6 raters with and without clinical information. One rater had a decrease in inter‐rater reliability from almost perfect (k = 1.0) to fair (k = 0.21) in the identification of interstitial infiltrate with the addition of clinical history.

CONCLUSIONS

Alveolar infiltrate and pleural effusion are findings with high intra‐ and inter‐rater reliability in the diagnosis of bacterial pneumonia. The addition of clinical information did not have a substantial impact on the reliability of these findings. Journal of Hospital Medicine 2013;8:359–364. © 2012 Society of Hospital Medicine
Adjuvant steroid therapy in community‐acquired pneumonia: A systematic review and meta‐analysis
Authors: Shafiq Majid , Mansoor Muhammad S. , Khan Adnan A. , Sohail M. Rizwan , Murad Mohammad H.
Published: November 2012

BACKGROUND

Community‐acquired pneumonia (CAP) is a leading cause of morbidity and mortality among adults. Although steroids appear to be beneficial in animal models of CAP, clinical trial data in humans are either equivocal or conflicting.

PURPOSE

Our purpose was to perform a systematic review and meta‐analysis of studies examining the impact of steroid therapy on clinical outcomes among adults admitted with CAP.

DATA SOURCES AND STUDY SELECTION

We identified randomized controlled trials (RCTs) through a systematic search of published literature up to July 2011.

DATA EXTRACTION

We estimated relative risks (RR) and weighted mean differences, pooled from each study using a random effects model.

DATA SYNTHESIS

Eight RCTs, comprising 1119 patients, met our selection criteria. Overall quality of the studies was moderate. Adjunctive steroid therapy had no effect on hospital mortality or length of stay in the intensive care unit, but reduced the overall length of hospital stay (RR: −1.21 days [95% confidence interval (CI): −2.12 to −0.29]). Less robust data also demonstrated reduced incidence of delayed shock (RR: 0.12 [95% CI: 0.03 to 0.41]) and reduced persistence of chest x‐ray abnormalities (RR: 0.13 [95% CI: 0.06 to 0.27]). A priori subgroup and sensitivity analyses did not alter these findings.

CONCLUSIONS

Moderate‐quality evidence suggests that adjunctive steroid therapy for adults hospitalized with CAP reduced the length of hospital stay but did not alter mortality. Journal of Hospital Medicine 2013;8:68–75. © 2012 Society of Hospital Medicine
Effect of nutrient‐based fertilisers of olive trees on olive oil quality
Authors: Tekaya Meriem , Mechri Beligh , Bchir Amani , Attia Faouzi , Cheheb Hechmi , Daassa Mohamed , Hammami Mohamed
Published: November 2012

Background

This work was conducted to determine the effects of two nutrient‐based fertilisers on the general physicochemical characteristics (including free fatty acid content, peroxide value and UV spectrophotometric characteristics), fatty acid profile, total phenols, o‐diphenols and phytosterol composition of olive oil. Foliar applications were carried out in two successive years and included four treatments: TC (control, without foliar nutrition), T1 (rich in nitrogen, applied at the start of vegetation, 10 days later and 20 days later), T2 (rich in boron, magnesium, sulfur and manganese, applied at the beginning of flowering and 10 days later) and T3 (T1 + T2). At the end of the experiment (after 2 years), oils were extracted and analysed.

Results

No effect was found on either general physicochemical characteristics or fatty acid composition. Foliar fertilisation caused a significant decrease in both polyphenol and o‐diphenol contents. Total sterol content was unaffected by foliar fertilisation. However, the phytosterol composition of the oil, particularly its β‐sitosterol level, was markedly improved after foliar nutrient application. Principal component analysis of the phytosterol composition showed discrimination between the control oil and the oils from T1, T2 and T3 treatments.

Conclusion

The results of this study extend the current knowledge of such cross‐talk between plant nutrition and quality of oil. © 2012 Society of Chemical Industry
Prediction of extraction efficiency in supported liquid membrane with a stagnant acceptor phase by means of artificial neural network
Authors: Michel Monika , Chimuka Luke , Kowalkowski Tomasz , Cukrowska Ewa M. , Buszewski Bogusław
Published: November 2012

An artificial neural network model of supported liquid membrane extraction process with a stagnant acceptor phase is proposed. Triazine herbicides and phenolic compounds were used as model compounds. The model is able to predict the compound extraction efficiency within the same family based on the octanol–water partition coefficient, water solubility, molecular mass and ionisation constant of the compound. The network uses the back‐propagation algorithm for evaluating the connection strengths representing the correlations between inputs (octanol–water partition coefficients logP, acid dissociation constant pKa, water solubility and molecular weight) and outputs (extraction efficiency in dihexyl ether and undecane as organic solvents). The model predicted results in good agreement with the experimental data and the average deviations for all the cases are found to be smaller than ±3%. Moreover, standard statistical methods were applied for exploration of relationships between studied parameters.
Developing an alcoholic‐assisted dispersive liquid–liquid microextraction for extraction of pentachlorophenol in water
Authors: Hadjmohammadi Mohammad Reza , Fatemi Mohammad Hossein , Shakeri Panteha
Published: November 2012

Optimization of alcoholic‐assisted dispersive liquid–liquid microextraction of pentachlorophenol (PCP) and determination of it with high‐performance liquid chromatography (UV‐Vis detection) was investigated. A Plackett‐Burman design and a central composite design were applied to evaluate the alcoholic‐assisted dispersive liquid–liquid microextraction procedure. The effect of seven parameters on extraction efficiency was investigated. The factor studied were type and volume of extraction and dispersive solvents, amount of salt, and agitation time. According to Plackett‐Burman design results, the effective parameters were type and volume of extraction solvent and agitation time. Next, a central composite design was applied to obtain optimal condition. The optimized conditions were obtained at 170‐μL 1‐octanol and 5‐min agitation time. The enrichment factor of PCP was 242 with limits of detection of 0.04 μg L−1. The linearity was 0.1–100 μg L−1 and the extraction recovery was 92.7%. RSD for intra and inter day of extraction of PCP were 4.2% and 7.8%, respectively for five measurements. The developed method was successfully applied for the determination of PCP in environmental water samples.
Identification and characterization of polycyclic aromatic hydrocarbons in coking wastewater sludge
Authors: Zhang Wanhui , Feng Chunhua , Wei Chaohai , Yan Bo , Wu Chaofei , Li Ning
Published: November 2012

GC‐MS analysis was performed on the coking sludge from a coking wastewater treatment plant (WWTP) to allow detailed chemical characterization of polycyclic aromatic hydrocarbons (PAHs). The identification and characterization of the isomers of PAHs was based on a positive match of mass spectral data of their isomers with mass spectra databases or based on a comparison of electron impact ionization mass spectra and retention times of target compounds with those reference compounds. In total, 160 PAH compounds including numerous N‐, O‐, S‐, OH‐, and Cl‐containing derivatives were positively identified for the first time. Quantitative analysis of target compounds was performed in the selected ion‐monitoring mode using the internal standard method. The total concentrations of selected compounds in the coking sludge samples from the anaerobic tank, aerobic tank, hydrolytic tank, and secondary clarifier of the WWTP ranged from 1690 ± 585 to 6690 ± 522 mg/kg, which were much higher than those in other industrial and municipal sludges. PAHs with four and five rings were found to be the dominant compounds, and diagnostic ratios of these compounds suggested that they had the characteristics of coal combustion and pyrolysis.
Magnetic solid‐phase extraction and ultrafast liquid chromatographic detection of Sudan dyes in red wines, juices, and mature vinegars
Authors: Yu Xi , Sun Ying , Jiang Chun‐Zhu , Gao Yan , Wang Yuan‐Peng , Zhang Han‐Qi , Song Da‐Qian
Published: November 2012

A nanocomposite of polystyrene‐coated magnetic nanoparticles was successfully synthesized and employed as adsorbent for magnetic solid‐phase extraction of four Sudan dyes (I, II III, and IV) in red wines, juices, and mature vinegars. The prepared magnetic nanoparticles with highly hydrophobic properties have excellent adsorption capacity for these lipophilic Sudan dyes. Extraction conditions were optimized. Experimental results showed that the recoveries of the four Sudan dyes were very satisfactory when 70 mg of polystyrene‐coated magnetic nanoparticles were used and the extraction could be completed within 20 min. It was proved that these magnetic nanoparticles can be reused after an easy washing process. By coupling the magnetic solid‐phase extraction with ultrafast liquid chromatography‐ultraviolet spectrometry, a rapid, green, effective, and sensitive method for the determination of Sudan dyes was developed. The LOD for Sudan I, Sudan II, Sudan III, and Sudan IV were 0.0039, 0.0063, 0.0057, and 0.017 ng/mL, respectively. Recoveries obtained by analyzing spiked water samples at three concentration levels (0.1, 1.0, and 10.0 ng/mL) were between 76.3 and 96.6%. The intra‐ and interday RSDs for the analytes were lower than 9.6%.
Determination of aromatic amines from textiles using dispersive liquid–liquid microextraction
Authors: Yang Lu , Yiwei Wang , Caiying Lou , Yan Zhu
Published: November 2012

A dispersive liquid–liquid microextraction procedure coupled with GC‐MS is described for preconcentration and determination of banned aromatic amines from textile samples. Experimental conditions affecting the microextraction procedure were optimized. A mixture of 30 μL chlorobenzene (extraction solvent) and 800 μL ACN (disperser solvent), 5 min extraction time, and 5 mL aqueous sample volume were chosen for the best extraction efficiency by the proposed procedure. Satisfactory linearity (with correlation coefficients >0.9962) and repeatability (<9.78%) were obtained for all 20 aromatic amines; detection limits attained were much lower than the standardized liquid–liquid method. The proposed method has advantages of being quicker and easier to operate, and lower consumption of organic solvent.
Pharmacokinetics of 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐D‐glucoside in rat using ultra‐performance LC‐quadrupole TOF‐MS
Authors: Zhao Ying‐Yong , Zhang Li , Feng Ya‐Long , Chen Dan‐Qian , Xi Zhi‐Hui , Du Xiao , Bai Xu , Lin Rui‐Chao
Published: November 2012

2,3,5,4′‐Tetrahydroxystilbene‐2‐O‐β‐D‐glucoside (THSG) from Polygoni multiflori has been demonstrated to possess a variety of pharmacological activities, including antioxidant, anti‐inflammatory and hepatoprotective activities. Ultra‐performance LC‐quadrupole TOF‐MS with MS Elevated Energy data collection technique and rapid resolution LC with diode array detection and ESI multistage MSn methods were developed for the pharmacokinetics, tissue distribution, metabolism, and excretion studies of THSG in rats following a single intravenous or oral dose. The three metabolites were identified by rapid resolution LC‐MSn. The concentrations of the THSG in rat plasma, bile, urine, feces, or tissue samples were determined by ultra‐performance LC‐MS. The results showed that THSG was rapidly distributed and eliminated from rat plasma. After the intravenous administration, THSG was mainly distributing in the liver, heart, and lung. For the rat, the major distribution tissues after oral administration were heart, kidney, liver, and lung. There was no long‐term storage of THSG in rat tissues. Total recoveries of THSG within 24 h were low (0.1% in bile, 0.007% in urine, and 0.063% in feces) and THSG was excreted mainly in the forms of metabolites, which may resulted from biotransformation in the liver.
Preparation and application of novel zwitterionic monolithic column for hydrophilic interaction chromatography
Authors: Liu Zhenghua , Peng Yongbo , Wang Tingting , Yuan Guangxin , Zhang Qiaoxuan , Guo Jialiang , Jiang Zhengjin
Published: November 2012

A novel zwitterionic hydrophilic porous monolithic stationary phase was prepared based on the thermal‐initiated copolymerization of N,N‐dimethyl‐N‐(3‐methacryl‐amidopropyl)‐N‐(3‐(sulfopropyl)ammonium betaine and ethylene glycol dimethacrylate. A typical hydrophilic separation mechanism was observed at a highly organic mobile phase (ACN >60%) on this optimized zwitterionic hydrophilic interaction chromatography (HILIC) monolithic stationary phase. Good permeability, stability, and column efficiency were observed on the final monolithic column. Additionally, a weak electrostatic interaction for charged analytes was confirmed in analysis of six benzoic acids by studying the influence of mobile phase pH and salt concentration on their retention behaviors on the obtained zwitterionic HILIC monolithic column. The optimized zwitterionic HILIC monolith exhibited good selectivity for a range of polar test analytes.
Encouraging Legal Help Seeking for Victims of Intimate Partner Violence: The Therapeutic Effects of the Civil Protection Order
Authors: Wright Caroline Vaile , Johnson Dawn M.
Published: November 2012

Civil protective orders (CPOs) are the most widely used justice system remedy for intimate partner violence (IPV), and were implemented to ensure safety and increase victim participation in the justice system. Limited data exists regarding the effectiveness of CPOs; however, theories of therapeutic jurisprudence argue that legal interventions in and of themselves can improve mental health outcomes. To test this hypothesis, we examined the effectiveness of having a CPO issued against one's abuser at improving the psychological sequelae of exposure to trauma. We used a longitudinal sample of female residents of battered women's shelters who had experienced IPV (N = 106; 55% African American). One‐way analyses of variance using gain scores indicated that PTSD symptoms (effect size ηp2 = .16) and incidents of sexual revictimization (effect size ηp2 = .09) decreased from baseline to 6‐months postshelter for women who had a CPO against their most recent abuser compared to women without a CPO. These results support theories of therapeutic jurisprudence, suggesting that having a CPO can improve mental health outcomes. Limitations and clinical implications of our findings are discussed, including arguing for a coordinated service system that incorporates both legal and psychological assistance to improve the mental health of victims of IPV.
Femtosecond plasma mediated laser ablation has advantages over mechanical osteotomy of cranial bone
Authors: Lo David D. , Mackanos Mark A. , Chung Michael T. , Hyun Jeong S. , Montoro Daniel T. , Grova Monica , Liu Chunjun , Wang Jenny , Palanker Daniel , Connolly Andrew J. , Longaker Michael T. , Contag Christopher H. , Wan Derrick C.
Published: November 2012

Background

Although mechanical osteotomies are frequently made on the craniofacial skeleton, collateral thermal, and mechanical trauma to adjacent bone tissue causes cell death and may delay healing. The present study evaluated the use of plasma‐mediated laser ablation using a femtosecond laser to circumvent thermal damage and improve bone regeneration.

Methods

Critical‐size circular calvarial defects were created with a trephine drill bit or with a Ti:Sapphire femtosecond pulsed laser. Healing was followed using micro‐CT scans for 8 weeks. Calvaria were also harvested at various time points for histological analysis. Finally, scanning electron microscopy was used to analyze the microstructure of bone tissue treated with the Ti:Sapphire laser, and compared to that treated with the trephine bur.

Results

Laser‐created defects healed significantly faster than those created mechanically at 2, 4, and 6 weeks post‐surgery. However, at 8 weeks post‐surgery, there was no significant difference. In the drill osteotomy treatment group, empty osteocyte lacunae were seen to extend 699 ± 27 µm away from the edge of the defect. In marked contrast, empty osteocyte lacunae were seen to extend only 182 ± 22 µm away from the edge of the laser‐created craters. Significantly less ossification and formation of irregular woven bone was noted on histological analysis for drill defects.

Conclusions

We demonstrate accelerated bone healing after femtosecond laser ablation in a calvarial defect model compared to traditional mechanical drilling techniques. Improved rates of early regeneration make plasma‐mediated ablation of the craniofacial skeleton advantageous for applications to osteotomy. Lasers Surg. Med. 44: 805–814, 2012. © 2012 Wiley Periodicals, Inc.
Renewable Polyols for Polyurethane Synthesis via Thiol‐ene/yne Couplings of Plant Oils
Authors: Lligadas Gerard
Published: November 2012

There is no doubt that nature offers an abundance of opportunities to polymer chemists for shaping structural and functional polymers in its wide variety of raw materials. Nowadays, plant oils and derivatives are in the spotlight of polyurethane technology and the design of novel biobased polyols derived from them is an active area of research. The contribution of this technology to sustainable development must go further than simply exploit renewable feedstock, and therefore must be aware of efficient click‐chemistry transformations exemplified by thiol‐ene/yne couplings. Within this contribution, these biobased materials, together with thiol‐ene/yne couplings are presented as a perfect ecofriendly combination to prepare hydroxyl building blocks for polyurethane technology.
In Situ AFM Investigation of Electrochemically Induced Surface‐Initiated Atom‐Transfer Radical Polymerization
Authors: Li Bin , Yu Bo , Zhou Feng
Published: November 2012

Electrochemically induced surface‐initiated atom‐transfer radical polymerization is traced by in situ AFM technology for the first time, which allows visualization of the polymer growth process. It affords a fundamental insight into the surface morphology and growth mechanism simultaneously. Using this technique, the polymerization kinetics of two model monomers were studied, namely the anionic 3‐sulfopropyl methacrylate potassium salt (SPMA) and the cationic 2‐(metharyloyloxy)ethyltrimethylammonium chloride (METAC). The growth of METAC is significantly improved by screening the ammonium cations by the addition of ionic liquid electrolyte in aqueous solution.
Possible effects of dietary polyphenols on sugar absorption and digestion
Authors: Williamson Gary
Published: November 2012

Excessive post‐prandial glucose excursions are a risk factor for developing diabetes, associated with impaired glucose tolerance. One way to limit the excursion is to inhibit the activity of digestive enzymes for glucose production and of the transporters responsible for glucose absorption. Flavonols, theaflavins, gallate esters, 5‐caffeoylqunic acid and proanthocyanidins inhibit α‐amylase activity. Anthocyanidins and catechin oxidation products, such as theaflavins and theasinsensins, inhibit maltase; sucrase is less strongly inhibited but anthocyanidins seem somewhat effective. Lactase is inhibited by green tea catechins. Once produced in the gut by digestion, glucose is absorbed by SGLT1 and GLUT2 transporters, inhibited by flavonols and flavonol glycosides, phlorizin and green tea catechins. These in vitro data are supported by oral glucose tolerance tests on animals, and by a limited number of human intervention studies on polyphenol‐rich foods. Acarbose is a drug whose mechanism of action is only through inhibition of α‐amylases and α‐glucosidases, and in intervention studies gives a 6% reduction in diabetes risk over 3 years. A lifetime intake of dietary polyphenols, assuming the same mechanism, has therefore a comparable potential to reduce diabetes risk, but more in vivo studies are required to fully test the effect of modulating post‐prandial blood glucose in humans.
Natural compounds regulate energy metabolism by the modulating the activity of lipid‐sensing nuclear receptors
Authors: Goto Tsuyoshi , Kim Young‐Il , Takahashi Nobuyuki , Kawada Teruo
Published: November 2012

Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin‐responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity‐induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity‐associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism‐related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid‐sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.
Ultrasound for carpal tunnel syndrome screening in manual laborers
Authors: Cartwright Michael S. , Walker Francis O. , Blocker Jill N. , Schulz Mark R. , Arcury Thomas A. , Grzywacz Joseph G. , Mora Dana , Chen Haiying , Marín Antonio J. , Quandt Sara A.
Published: November 2012

Introduction

Manual laborers are at increased risk for carpal tunnel syndrome (CTS), and a combination of history, physical examination, and nerve conduction studies is often used to screen for CTS in this population. Neuromuscular ultrasound may be a better screening tool, because it is painless. In this study we compare the accuracy of nerve conduction studies and ultrasound for CTS screening.

Methods

Five hundred thirteen manual laborers were screened prospectively for CTS using nerve conduction studies and neuromuscular ultrasound, and the accuracy of the 2 techniques was compared using the Katz hand diagram as the diagnostic standard.

Results

The ROC curves for the 2 techniques were not significantly different (P = 0.542), indicating that the approaches had similar diagnostic accuracy.

Conclusions

Neuromuscular ultrasound is a painless technique that has diagnostic accuracy similar to nerve conduction studies and can be used to screen large populations at risk for CTS. Muscle Nerve, 2013
Activin‐βc reduces reproductive tumour progression and abolishes cancer‐associated cachexia in inhibin‐deficient mice
Authors: Gold Elspeth , Marino Francesco Elia , Harrison Craig , Makanji Yogeshwar , Risbridger Gail
Published: November 2012

Activins are involved in the regulation of a diverse range of physiological processes including development, reproduction, and fertility, and have been implicated in the progression of cancers. Bioactivity is regulated by the inhibin α‐subunit and by an activin‐binding protein, follistatin. The activin‐βC subunit was not considered functionally significant in this regard due to an absence of phenotype in knockout mice. However, activin‐βC forms heterodimers with activin‐βA and activin‐C antagonizes activin‐A in vitro. Thus, it is proposed that overexpression, rather than loss of activin‐βC, regulates activin‐A bioactivity. In order to prove biological efficacy, inhibin α‐subunit knockout mice (α‐KO) were crossed with mice overexpressing activin‐βC (ActC++). Deletion of inhibin leads to Sertoli and granulosa cell tumours, increased activin‐A, and cancer‐associated cachexia. Therefore, cachexia and reproductive tumour development should be modulated in α‐KO/ActC++ mice, where excessive activin‐A is the underlying cause. Accordingly, a reduction in activin‐A, no significant weight loss, and reduced incidence of reproductive tumours were evident in α‐KO/ActC++ mice. Overexpression of activin‐βC antagonized the activin signalling cascade; thus, the tumourigenic effects of activin‐A were abrogated. This study provides proof of the biological relevance of activin‐βC. Being a regulator of activin‐A, it is able to abolish cachexia and modulate reproductive tumour development in α‐KO mice.
High incidence of mammary intraepithelial neoplasia development in Men1‐disrupted murine mammary glands
Authors: Seigne Christelle , Auret Magdalena , Treilleux Isabelle , Bonnavion Rémy , Assade Fouzia , Carreira Christine , Goddard‐Léon Sophie , Lavergne Emilie , Chabaud Sylvie , Garcia Amandine , Mazoyer Sylvie , Lu Jieli , Bachelot Thomas , Frappart Lucien , Zhang Chang Xian
Published: November 2012

Mutations of the MEN1 tumour suppressor gene predispose patients to the development of multiple endocrine neoplasia type 1 (MEN1) syndrome, which is characterized by multiple endocrine tumours, including prolactinomas. The recent findings of the interaction between menin, encoded by the MEN1 gene, and the oestrogen receptor, as well as the observation of rare cases of mammary carcinomas in our heterozygous Men1 mutant mice, led us to investigate a putative tumour suppressor function of the Men1 gene in mouse mammary cells by disrupting the gene in luminal epithelial cells. A significantly higher incidence of mammary intraepithelial neoplasia (MIN) was observed in mutant WapCre‐Men1F/F mice (51.5%) than in WapCre‐Men1+/+ (0%) or Men1F/F (7.1%) control mice. The majority of MIN observed in the mutant mice displayed complete menin inactivation. Because of the leakage of WapCre transgene expression, prolactinomas were observed in 83.3% of mutant mice, leading to premature death. As there was no correlation between MIN development and elevated serum prolactin levels, and phospho‐STAT5 expression was decreased in mammary lesions, the increased incidence of MIN lesions was most likely due to Men1 disruption rather than to prolactinoma development. Interestingly, in MIN lesions, we found a decrease in membrane‐associated E‐cadherin and beta‐catenin expression, the latter of which is a menin partner. Finally, reduced menin expression was found in a large proportion of two independent cohorts of patients with breast carcinomas. Taken together, the current work indicates a role of Men1 inactivation in the development of mammary pre‐cancerous lesions in mice and a potential role in human mammary cancer.
Continuous glucose monitoring: the clinical picture. How to interpret and use the data
Authors: Hammond Peter
Published: November 2012

There is a limited evidence base as to the benefits of continuous glucose monitoring (CGM) in clinical practice, but it is clear that in order to realise improvements in glycaemic control when using CGM there is a requirement for both health care professionals and patients to have the ability to interpret the data obtained from CGM.

This article describes a personal approach to analysing CGM data using a structured approach and reporting tool, with examples to demonstrate how this system is implemented in practice. By viewing the daily overlay, then breaking the CGM traces into overnight, fasting/pre‐meal and post‐meal phases, and finally looking at the impact of other factors such as exercise, alcohol and work patterns, the user can be educated to make changes to both their insulin regimen and lifestyle to optimise glycaemic control. Those offered CGM as a real‐time adjunct to their intensive insulin regimen need to have such a structured approach to get positive re‐inforcement and thus use CGM sufficiently frequently to gain real benefit from it.
Copyright © 2012 John Wiley & Sons.
Network analysis of drug prescriptions
Authors: Cavallo Pierpaolo , Pagano Sergio , Boccia Giovanni , De Caro Francesco , De Santis Mario , Capunzo Mario
Published: November 2012

Purpose

Networks exist in many different aspects of the world, at social, economical, biological, and molecular levels. Network science studies their parameters, or quantitative indicators; its instruments make it possible to draw and analyze networks from a mathematical perspective.

The present study is an attempt to apply network science techniques to the drug prescription process, a typical subject of Epidemiology for Public Health studies.

Methods

A drug prescription network was created using the set of drug prescriptions written during a 6‐month period by a group of 99 general practitioners (GPs) operating in Italy. In this network, named co‐prescription network, each drug represented a node, and different drugs prescribed to the same patient at the same moment were considered linked together.

Drug prescription data for a total of 42 965 patients and 631 232 drug packages were studied.

A number of co‐prescription networks were obtained and analyzed on the basis of different subsets of patients by age and gender. The network parameters were measured and compared for the various subsets.

Results

All the drug prescription networks studied showed scale invariance behavior. The age‐ and gender‐related co‐prescription networks showed different patterns, with different levels of complexity.

Conclusions

The present study shows that the drug prescription process has specific network aspects and dynamics and, more generally, that it is possible to apply instruments of network science to study public health phenomena from a new, different perspective. Further studies should be encouraged and performed. Copyright © 2012 John Wiley & Sons, Ltd.
Proteomic profiling of expression of proteasomal subunits from livers of mice treated with diethylnitrosamine
Authors: Yuan Fuqiang , Lu Jia , You Pan , Yang Zengming , Yang Pengyuan , Ma Qiling , Tao Tao
Published: November 2012

The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Diethylnitrosamine is metabolized primarily in the liver by cytochrome P‐450 and can cause DNA damage. The 26S proteasome is a large proteolytic complex that degrades ubiquitinated proteins, and regulates many physiological processes. We used proteomics‐based approaches to examine expressional differences of liver proteasomal subunits from diethylnitrosamine‐treated mice. The expression of most proteasomal subunits was observed to be upregulated in the analysis of 2DE and MALDI‐TOF MS/MS. Some of these differentially expressed proteasomal subunits were further confirmed by Western blot, RT‐PCR, and immunohistochemistry. Our results provided useful information on the relationship between the proteasomal complex and related diseases.
An artificial neural network approach to improving the correlation between protein energetics and the backbone structure
Authors: Fawcett Timothy M. , Irausquin Stephanie J. , Simin Mikhail , Valafar Homayoun
Published: November 2012

Computational approaches to modeling protein structures have made significant advances over the past decade. However, the current limitation in modeling protein structures is to produce protein structures consistently below the limit of 6 Å compared to their native structure. Therefore, improvement of protein structures consistently below the 6 Å limit using simulation of biophysical forces is of significant interest. Current protein force fields such as those implemented in CHARMM, AMBER, and NAMD have been deemed complete, yet their use in ab initio approaches to protein structure determination has been unsuccessful. Here, we introduce a new approach in evaluation of protein structures based on analysis of energy profiles produced by the SCOPE software package. The latest version of SCOPE produces a hydrogen bond profile that is substantially more informative than a single hydrogen bond energy value. We demonstrate how analysis of SCOPE's energy profile by an artificial neural network shows a significant improvement compared to the traditional force‐based approaches to evaluation of structures. The artificial neural network based analysis of SCOPE's energy profile showed identification of structures to within the range of 1.5–3.0 Å of the native structure. These results have been obtained by testing structures in the same Homology, Topology, Architecture, or Class of the CATH family.
Fast algorithm for population‐based protein structural model analysis
Authors: Zhang Jingfen , Xu Dong
Published: November 2012

De novo protein structure prediction often generates a large population of candidates (models), and then selects near‐native models through clustering. Existing structural model clustering methods are time consuming due to pairwise distance calculation between models. In this paper, we present a novel method for fast model clustering without losing the clustering accuracy. Instead of the commonly used pairwise root mean square deviation and TM‐score values, we propose two new distance measures, Dscore1 and Dscore2, based on the comparison of the protein distance matrices for describing the difference and the similarity among models, respectively. The analysis indicates that both the correlation between Dscore1 and root mean square deviation and the correlation between Dscore2 and TM‐score are high. Compared to the existing methods with calculation time quadratic to the number of models, our Dscore1‐based clustering achieves a linearly time complexity while obtaining almost the same accuracy for near‐native model selection. By using Dscore2 to select representatives of clusters, we can further improve the quality of the representatives with little increase in computing time. In addition, for large size (~500 k) models, we can give a fast data visualization based on the Dscore distribution in seconds to minutes. Our method has been implemented in a package named MUFOLD‐CL, available at http://mufold.org/clustering.php.