bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipase‐catalyzed synthesis of polymeric prodrugs of nonsteroidal anti‐inflammatory drugs
Authors: Qian Xueqi , Wu Qi , Xu Fangli , Lin Xianfu
Published: September 2012

Because of the potential application of prodrugs of nonsteroidal anti‐inflammatory drugs (NSAIDs), Candida antarctica lipase B (CAL‐B) catalyzed polycondensation of profen‐containing diol monomers and diesters were designed to prepare a series of biodegradable polymeric prodrugs composed of NSAID branches and poly(amide‐co‐ester) backbone. The structure of the products was confirmed by Fourier transform infrared spectroscopy, NMR, and gel permeation chromatography (GPC). The reaction conditions of polymerization, such as the enzyme source, amount of catalyst, and temperature, were optimized. The molecular weights of resultant copolymers were 2170–13,270 g/mol, with corresponding polydispersities from 1.17 to 2.4. The copolymers had relatively high drug loadings of 44.7–59.7 wt % because every repeat unit contained one drug molecule. The strategy of enzymatic polymerization appeared to be quite general and accommodated a large number of comonomer substrates with various chain lengths and substituents. The optically pure (R)‐naproxen monomer was demonstratively incorporated into the corresponding copolymers with the developed synthesis strategy. The in vitro study showed that the polyester could release the drug effectively under physiological conditions with enzyme, which indicated that the obtained product could be a promising prodrug for extending pharmacological effects by delayed drug release. With GPC analysis, we confirmed that the prodrug was completely degradable in aqueous solution. The attractive features of the copolymer were its high drug loading, biodegradability, and biocompatibility. The high tolerance of the CAL‐B toward drug groups, as described in this article, provides a new route for synthesizing polymeric drugs with potential biomedical applications in mild conditions and for reducing environmental impact. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Synthesis and properties of an insoluble chitosan resin modified by azamacrocycle copper(II) complex for protein hydrolysis
Authors: Wang Xingyu , Wang Dongfeng , Liang Peng , Liang Xingguo
Published: September 2012

We reported the synthesis process and the proteolytic ability of a novel crosslinked chitosan resin modified by azamacrocycle copper complex (CMCR). Characterization of CMCR showed that the Cu(II)Cyclen complex had successfully bound to the resin matrix covalently. Its proteolytic activity toward peptide bonds was evaluated by investigating the hydrolysis of bovine serum albumin in heterogeneous media. The maximum‐observed pseudo‐first‐order rate constant (kobs) was achieved under 60°C, pH 6.0, where protein was hydrolyzed into smaller peptides and amino acids confirmed by SDS–PAGE and ninhydrin reaction. The results indicated that the hydrolyzing efficiency delivered by CMCR was 4 × 105 times higher than that of spontaneous hydrolysis. CMCR also featured a desirable stability for chelating Cu2+ ions, which paved the way for its feasible recovery process and good reusability. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci, 2013
Development and characterization of new AR glass fiber‐reinforced cements with potential medical applications
Authors: Furtos Gabriel , Tomoaia‐Cotisel Maria , Baldea Bogdan , Prejmerean Cristina
Published: September 2012

The aim of this study was to obtain and investigate new biomedical glass fiber resin cements with improved mechanical properties and radiopacity, using alkaline‐resistant (AR) glass fibers. New light‐curing, self‐curing, and dual‐curing resin cements were obtained from AR glass fibers and BaSO4 powder mixed with 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloyloxypropoxy)‐phenyl]propane and triethyleneglycol dimethacrylate monomers at different weight ratios, such as 5/20/75, 10/20/70, 20/20/60. The newly obtained cements were investigated for mechanical properties—compressive yield strength (CYS), compressive modulus (CM), diametral tensile strength (DTS)—as well as for radiopacity. Slight increases in CYS, CM, DTS and improved radiopacity with increasing amount of glass fibers were observed. The mechanical properties were found to increase in the order light‐curing < self‐curing < dual‐curing. SEM images support the reinforcement of resin cements by glass fibers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Effect of PEO on the network structure of PVA hydrogels prepared by freezing/thawing method
Authors: Lian Zhe , Ye Lin
Published: September 2012

Poly(vinyl alcohol) (PVA)/poly(ethylene oxide) (PEO) hydrogels were prepared by freezing/thawing method for application as a wound dressing. The effect of PEO content on the network structure of PVA hydrogel was investigated in terms of crystalline and reological properties. It was found that a low amount of PVA crystallites were present in PVA/PEO hydrogels. With increasing content of PEO, the crstallinity of PVA hydrogel decreased, but the apparent dimensions of crystallites increased. The shear storage modulus (G′) decreased slightly with the increasing temperature within 30–50°C, probably resulting from the breaking of the hydrogen bonding; while it decreased sharply within 50–70°C, probably resulting from the melt of the crystallites of PVA hydrogel. The physical crosslinking density (Dpc) increased with decreasing PEO content, while decreased more dramatically with increasing temperature, indicating that hydrogen bonding was easier to be broken at high temperature. At very low strain amplitudes, the loss modulus (G″) of the hydrogel is lower than the storage modulus (G′) and G′ is independent of the strain amplitude, indicating that the deformation imposed on the network structure is entirely reversible. With increasing content of PEO, G′ at low frequency decreased, and the mesh size (Lc) increased, indicating of the decrease of the physical crosslinking density of PVA/PEO hydrogels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Swelling behavior of physical and chemical DNA hydrogels
Authors: Karacan Pinar , Cakmak Husniye , Okay Oguz
Published: September 2012

DNA hydrogels were prepared from aqueous solutions of double‐stranded DNA (about 2000 base pairs long) by physical and chemical means. Physical gels were obtained via denaturation–renaturation cycle of 5% aqueous DNA solutions between 25 and 90°C. Although physical DNA gels exhibit a high modulus of elasticity, the crosslinks holding the DNA network together are destroyed during the expansion of gels in water or in dilute salt solutions. It was shown that these gels can be used for the controlled release of DNA in aqueous media. Chemical DNA gels formed using ethylene glycol diglycidyl ether crosslinker are stable in water with a wide range of swelling ratios that could be adjusted by the amount of DNA at the gel preparation. Swelling behavior of chemical DNA gels in acetone/water mixtures as well as in aqueous salt solutions is very similar to that of synthetic polyelectrolyte hydrogels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Hydrolysis of birch wood by simultaneous ball milling, dilute citric acid, and fungus Penicillium simplicissimum treatment at room temperature
Authors: Yuan Li , Chen Zhenhua , Zhu Yonghua , Liu Xuanming , Liao Hongdong , Chen Ding
Published: September 2012

In this study, birch wood chips were treated in one‐step ball milling (BM) hydrolysis with dilute citric acid and fungus Penicillium simplicissimum at room temperature and atmospheric pressure. An efficient conversion process for the production of fermentable sugars from woody biomasses using wet BM system was developed, in which wood lignocellulose was hydrolyzed into reducing sugars with the total yield of 245.3 mg/g wood. The concentrations of several major substances in the hydrolyzate were discussed in detail. The yields of the monomeric sugars were notably increased in the presence of fungus P. simplicissimum. Corresponding structure transformations before and after milling were analyzed by X‐ray diffraction, UV spectroscopy, transmission Fourier transform infrared spectroscopy, and environmental scanning electron microscopy clearly indicated that this combined treatment could be attributed to the crystalline and chemical structure changes of wood lignocellulose during BM. When compared with traditional method of BM, this work showed a more simple, novel, and environmental friendly way in mechanochemical treatment of lignocellulosic biomass, especially woody biomass. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Morphological diversity and nanofiber networks of poly(p‐oxybenzoyl) generated by phase separation during copolymerization
Authors: Ichimori Toshimitsu , Mizuma Kenta , Uchida Tetsuya , Yamazaki Shinichi , Kimura Kunio
Published: September 2012

Poly(p‐oxybenzoyl) (POB) precipitates prepared by reaction‐induced phase separation during copolymerization exhibit wide variety of morphologies such as fibril, needle, slab, spindle, and sphere. The morphology is significantly influenced by the copolymerization conditions of structure of trifunctional comonomers, copolymerization ratio, solvent, concentration, and temperature of the polymerization. Among them, POB nanofiber networks like a texture of nonwoven fabrics are obtained only by the polymerization of 4‐acetoxybenzoic acid with 3,5‐diacetoxybenzoic acid (DABA) in aromatic solvent at a concentration of 1.0–2.0% at the content of DABA in feed of 10–20 mol % at 320°C. The network is comprised of fibrillar crystals connected each other at spherical nodal points. The diameters of the fibers are 90–129 nm. This network is highly crystalline and the molecules are aligned along the long direction of the fibers. Various parameters characterized the networks can be controlled by the polymerization concentration. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as a screening method for the prevention of colorectal cancer
Authors: Littlejohn C , Hilton S , Macfarlane G J , Phull P
Published: September 2012

Background

Colorectal cancer is a significant cause of death. Removal of precancerous adenomas, and early detection and treatment of cancer, has been shown to reduce the risk of death. The aim of this review and meta-analysis was to determine whether flexible sigmoidoscopy (FS) is an effective population screening method for reducing mortality from colorectal cancer.

Methods

MEDLINE (1946 to December 2012) and Embase (1980–2012, week 15) were searched for randomized clinical trials in which FS was used to screen non-symptomatic adults from a general population, and FS was compared with either no screening or any other alternative screening methods. Meta-analysis was carried out using a random-effects Mantel–Haenzsel model.

Results

Twenty-four papers met the inclusion criteria, reporting results from 14 trials. Uptake of FS was usually lower than that for stool-based tests, although FS was more effective at detecting advanced adenoma and carcinoma. FS reduced the incidence of colorectal cancer after screening, and long-term mortality from colorectal cancer, compared with no screening in a selected population. Compared with stool-based tests in a general population, FS was associated with fewer interval cancers.

Conclusion

FS is efficacious at reducing colorectal cancer mortality compared with no screening. It is more effective at detecting advanced adenoma and carcinoma than stool-based tests. FS may be compromised by poorer uptake. Introduction of FS as a screening method should be done on a pilot basis in populations in which it is not currently used, and close attention should be paid to maximizing uptake. The relative risk of adverse events with FS compared with stool-based tests should be quantified, and its real-world effectiveness evaluated against the most effective stool-based tests.
Systematic review and meta-analysis of safety of laparoscopicversusopen appendicectomy for suspected appendicitis in pregnancy
Authors: Wilasrusmee C , Sukrat B , McEvoy M , Attia J , Thakkinstian A
Published: September 2012

Background

Laparoscopic appendicectomy has gained wide acceptance as an alternative to open appendicectomy during pregnancy. However, data regarding the safety and optimal surgical approach to appendicitis in pregnancy are still controversial.

Methods

This was a systematic review and meta-analysis of studies comparing laparoscopic and open appendicectomy in pregnancy identified using PubMed and Scopus search engines from January 1990 to July 2011. Two reviewers independently extracted data on fetal loss, preterm delivery, wound infection, duration of operation, hospital stay, Apgar score and birth weight between laparoscopic and open appendicectomy groups.

Results

Eleven studies with a total of 3415 women (599 in laparoscopic and 2816 in open group) were included in the analysis. Fetal loss was statistically significantly worse in those who underwent laparoscopy compared with open appendicectomy; the pooled relative risk (RR) was 1·91 (95 per cent confidence interval (c.i.) 1·31 to 2·77) without heterogeneity. The pooled RR for preterm labour was 1·44 (0·68 to 3·06), but this risk was not statistically significant. The mean difference in length of hospital stay was − 0·49 (−1·76 to − 0·78) days, but this was not clinically significant. No significant difference was found for wound infection, birth weight, duration of operation or Apgar score.

Conclusion

The available low-grade evidence suggests that laparoscopic appendicectomy in pregnant women might be associated with a greater risk of fetal loss.
Preoperative cardiopulmonary exercise testing and risk of early mortality following abdominal aortic aneurysm repair8
Authors: Hartley R A , Pichel A C , Grant S W , Hickey G L , Lancaster P S , Wisely N A , McCollum C N , Atkinson D
Published: September 2012

Background

Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity. The aim of this study was to assess whether preoperative CPET identifies patients at risk of early death following elective open and endovascular abdominal aortic aneurysm (AAA) repair.

Methods

Prospective data were collected from a pilot study between September 2005 and February 2007, and from all patients who underwent CPET before elective AAA repair at two vascular centres between February 2007 and November 2011. Symptom-limited, maximal CPET was performed on each patient. Univariable and multivariable analyses were used to identify risk factors for 30- and 90-day mortality.

Results

Some 415 patients underwent CPET before elective AAA repair. Anaerobic threshold (AT), peak oxygen consumption (peak V̇o2) and ventilatory equivalents for carbon dioxide were associated with 30- and 90-day mortality on univariable analysis. On multivariable analysis, open repair (odds ratio (OR) 4·92, 95 per cent confidence interval 1·55 to 17·00; P = 0·008), AT below 10·2 ml per kg per min (OR 6·35, 1·84 to 29·80; P = 0·007), anaemia (OR 3·27, 1·04 to 10·50; P = 0·041) and inducible cardiac ischaemia (OR 6·16, 1·48 to 23·07; P = 0·008) were associated with 30-day mortality. Anaemia, inducible cardiac ischaemia and peak V̇o2 less than 15 ml per kg per min (OR 8·59, 2·33 to 55·75; P = 0·005) were associated with 90-day mortality on multivariable analysis. Patients with two or more subthreshold CPET values were at increased risk of both 30- and 90-day mortality.

Conclusion

An AT below 10·2 ml per kg per min, peak V̇o2 less than 15 ml per kg per min and at least two subthreshold CPET values identify patients at increased risk of early death following AAA repair.
Progress and challenges in improving surgical outcomes1
Authors: Birkmeyer J D
Published: September 2012

A lot of effort still needed
Psychopathic Traits in Females and Males across the Globe
Authors: Neumann Craig S. , Schmitt David S. , Carter Rachel , Embley Iva , Hare Robert D.
Published: September 2012

The current study examined the prevalence and structure of psychopathic traits in females and males using a very large world sample (N = 33,016, females = 19,183). Psychopathic traits were assessed with the Self‐Report Psychopathy (SRP) scale, and structural equation modeling (SEM) was used to test the four‐factor model of psychopathy (interpersonal, affective, lifestyle, antisocial) both in the total sample and in the separate samples of females and males. Multi‐sample confirmatory factor analysis was used to test for invariance of model parameters across sex as well as across females from different world regions. Inferential statistics were used to examine how the mean‐level average of the four SRP facets varied as a function of culture and sex. Finally, the SRP data were linked to objective world health data (e.g., mortality, fertility, gross domestic product) from relevant world regions. The results indicated good support for the four‐factor model, as well as invariance across sex and reasonably good evidence of invariance across females from different world regions. Variation in the elevation of SRP facet scores across major world regions suggested that cultural factors moderated the expression of the level of psychopathic propensities and that these traits were strongly correlated with the world health data. Copyright © 2012 John Wiley & Sons, Ltd.
Are Self‐Report Measures of Adaptive Functioning Appropriate for those High in Psychopathic Traits?
Authors: Young‐Lundquist Bethany A. , Boccaccini Marcus T. , Simpler Amber
Published: September 2012

There is ongoing debate about the methods that evaluators should use to assess the adaptive functioning of an individual in an Atkins claim, including the appropriateness of using self‐report measures and extent to which adaptive functioning measures are valid for persons with a history of violent offending. This study examined whether offenders' self‐report adaptive functioning scores tended to decrease as their level of psychopathic traits increased. Eighty‐five male felony probationers completed the self‐report version of the Adaptive Behavior Assessment System – II (ABAS‐II: Harrison & Oakland, 2003), the Psychopathic Personality Inventory – Revised (PPI‐R: Lilienfeld & Widows, 2005), and a brief intelligence screening measure. ABAS‐II composite scores were negatively correlated with PPI‐R Self‐Centered Impulsivity and Coldheartedness scores, but positively correlated with Fearless Dominance scores. These relationships appeared to be due, in part, to over‐reporting symptoms of impairment across measures, suggesting that scores on self‐report adaptive functioning measures may be especially susceptible to feigning. Copyright © 2012 John Wiley & Sons, Ltd.
A fast automatic frequency calibration technique for a 2–6 GHz frequency synthesizer
Authors: Jeong Chan‐Young , Choi Dong‐Ho , Yoo Changsik
Published: September 2012

A fast automatic frequency calibration (AFC) technique is described. For fast AFC operation while eliminating the uncertainty of the initial phase relationship between the reference clock and voltage‐controlled oscillator output, two‐phase reference clocks are employed. The proposed AFC scheme is applied to a 2–6 GHz frequency synthesizer. The frequency synthesizer is implemented in a 0.18 µm complementary metal–oxide–semiconductor process and occupies 0.92 mm2 while the AFC occupies only 0.01 mm2. The AFC operation is completed in less than 1.6 µs. Copyright © 2012 John Wiley & Sons, Ltd.
What does population structure analysis reveal about the Pterostylis longifolia complex (Orchidaceae)?
Authors: Janes Jasmine K. , Steane Dorothy A. , Vaillancourt René E.
Published: September 2012

Morphologically similar groups of species are common and pose significant challenges for taxonomists. Differences in approaches to classifying unique species can result in some species being overlooked, whereas others are wrongly conserved. The genetic diversity and population structure of the Pterostylis longifolia complex (Orchidaceae) in Tasmania was investigated to determine if four species, and potential hybrids, could be distinguished through genomic AFLP and chloroplast restriction‐fragment‐length polymorphism (RFLP) markers. Analysis of molecular variance (AMOVA) results indicated that little genetic variation was present among taxa, whereas PCoA analyses revealed genetic variation at a regional scale irrespective of taxa. Population genetic structure analyses identified three clusters that correspond to regional genetic and single taxon‐specific phenotypic variation. The results from this study suggest that “longifolia” species have persisted throughout the last glacial maximum in Tasmania and that the complex may be best treated as a single taxon with several morphotypes. These results could have serious evolutionary and conservation implications as taxonomic changes could result in the instatement of a single, widespread taxon in which rarer morphotypes are not protected.
Effects of the peroxisome proliferator di(2-ethylhexyl)phthalate on cell turnover and peroxisome proliferation in primary chick embryo hepatocytes
Authors: Arias Elio
Published: September 2012

The peroxisome proliferator (PP) di(2-ethylhexyl)phthalate (DEHP) is widely used as a plasticizer and can contaminate air, water, and soil. As yet, no data have been published on its potential to induce changes in cell growth of nonmammalian hepatocytes. In the present study, the effects of DEHP on cell turnover and induction of peroxisome proliferation were evaluated in primary hepatocyte cultures from chick embryos. Cells were treated after attachment with 0, 25, 50, 75, and 100 µM DEHP for up to 96 h. S-phase increased significantly (p < 0.01) from a background level of 5.5 ± 0.1% in solvent-control hepatocytes to a maximum level of 7.1 ± 0.1% in cells exposed for 48 h to 100 µM DEHP and decreased to near 6% by 96 h. Lower (p < 0.05) levels of induction were seen at 50 and 75 µM DEHP. Spontaneous apoptosis showed a slight (p < 0.05) decrease in hepatocytes treated with ≥75 µM dosages, as measured at 72 to 96 h. Induction of peroxisome proliferation was observed for cultures treated with ≥75 µM dosages at 48 h onwards. The results of the present study indicate that avian species may be responsive to the effects of PPs and may thus be affected by the presence of DEHP in the environment, but that this species is less sensitive than rodents. Environ. Toxicol. Chem. 2012; 31: 2856–2860. © 2012 SETAC
Bridging environmental mixtures and toxic effects
Authors: Allan Sarah E. , Smith Brian W. , Tanguay Robert L. , Anderson Kim A.
Published: September 2012

Biological Response Indicator Devices Gauging Environmental Stressors (BRIDGES) is a bioanalytical tool that combines passive sampling with the embryonic zebrafish developmental toxicity bioassay to provide a quantitative measure of the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs), which sequester and concentrate bioavailable organic contaminants from the environment, were deployed in the Willamette and Columbia Rivers within and outside of the Portland Harbor Superfund site in Portland, OR, USA. Six sampling events were conducted in the summer and fall of 2009 and 2010. Passive sampling device extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds and screened for 1,201 chemicals of concern using deconvolution-reporting software. The developmental toxicity of the extracts was analyzed using the embryonic zebrafish bioassay. The BRIDGES tool provided site-specific, temporally resolved information about environmental contaminant mixtures and their toxicity. Multivariate modeling approaches were applied to paired chemical and toxic effects data sets to help unravel chemistry–toxicity associations. Modeling elucidated spatial and temporal trends in PAH concentrations and the toxicity of the samples and identified a subset of PAH analytes that were the most highly correlated with observed toxicity. Although the present study highlights the complexity of discerning specific bioactive compounds in complex mixtures, it demonstrates methods for associating toxic effects with chemical characteristics of environmental samples. Environ. Toxicol. Chem. 2012; 31: 2877–2887. © 2012 SETAC
Intraframe quantization of speech line spectrum pairs for code‐excited linear prediction based coders in packet networks
Authors: Merazka Fatiha
Published: September 2012

This paper proposes intraframe quantization schemes of line spectrum pair parameters to improve frame erasures for the ITU‐T G.723.1 coder. The standard ITU‐T G.723.1 coder uses an interframe quantization of the line spectrum pair parameters, which causes error propagation to the next frames. Simulation results show that our intraframe quantization schemes coding is much more robust to frame erasures than the embedded method in ITU‐T G.723.1, and a typical improvement of 0.4 dB on average spectral distortion can be obtained with 40% packet loss. Enhanced modified bark spectral distortion tests, under various packet loss conditions, confirm that our proposed method is superior to the interframe algorithm embedded in the ITU‐T G.723.1 coder of over 1.6. Copyright © 2012 John Wiley & Sons, Ltd.
Oncogenic PIK3CA mutations in lobular breast cancer progression
Authors: Christgen Matthias , Noskowicz Monika , Schipper Elisa , Christgen Henriette , Heil Charlotte , Krech Till , Länger Florian , Kreipe Hans , Lehmann Ulrich
Published: September 2012

Infiltrating lobular breast cancer (ILBC) is a tumor‐biologically distinct breast cancer subtype. A high frequency of oncogenic PIK3CA mutations has been reported in ILBC, which may allow for targeted therapy with newly developed PI3K inhibitors. This is of particular clinical relevance for ILBC patients, who have failed to respond to current treatment regimes and suffer from tumor recurrence or dissemination. In anticipation of this therapeutic strategy, we investigated PIK3CA mutations in ILBC with special reference to late stage tumor progression. A total of 88 ILBCs from 73 patients, including primary tumors (PTs, n = 43), ipsilateral locally recurrent tumors (LRTs, n = 15), and distant organ metastases (DOMs, n = 30), were compiled on tissue microarrays. Established ILBC marker proteins were evaluated by immunohistochemistry and PIK3CA hot spot mutations in exons 9 and 20 by direct sequencing. Matched PT/LRT, PT/DOM, and DOM/DOM cases were characterized on a patient‐by‐patient basis. Following correction for redundant patient representations, mutation frequencies were compared in PTs versus LRTs or DOMs. Nearly all specimens were E‐cadherin‐negative (99%), estrogen receptor (ER)‐positive (91%), and lacked basal epithelial markers (100%), demonstrating correct ILBC classification. PIK3CA mutations were detected in 32/88 (36%) specimens. The mutation rate was similar in PTs (33%) and DOMs (26%, P = 0.769), but approximately two‐fold increased in LRTs (69%, P = 0.022). Consistently, matched PT/LRT and LRT/DOM cases showed additional PIK3CA mutations in LRTs. Intriguingly, these findings imply that PIK3CA mutations are positively selected for during ILBC progression to local recurrence but not distant metastasis, which may have clinical implications for PI3K inhibitor‐based therapy. © 2012 Wiley Periodicals, Inc.
The Paleoenvironment and Lithic Taphonomy of Shi’Bat Dihya 1, a Middle Paleolithic Site in Wadi Surdud, Yemen
Authors: Sitzia Luca , Bertran Pascal , Boulogne Stéphane , Brenet Michel , Crassard Rémy , Delagnes Anne , Frouin Marine , Hatté Christine , Jaubert Jacques , Khalidi Lamya , Messager Erwan , Mercier Norbert , Meunier Alain , Peigné Stéphane , Queffelec Alain , Tribolo Chantal , Macchiarelli Roberto
Published: September 2012

The Shi'bat Dihya 1 site in western Yemen, dated by optically stimulated luminescence to 55 ka, provides insight into the Middle Paleolithic peopling of the Arabian Peninsula. The archaeological layer is interstratified within thick, sandy silt floodplain deposits filling a piedmont basin. Luminescence dates, lack of soil development, and gypsum precipitation indicate a high accretion rate of the floodplain during Marine Isotope Stage 3, in connection with a (semi)‐arid environment. Rapid overbank sedimentation was likely a result of the remobilization of loess material deposited on the Yemeni Great Escarpment at the periphery of the adjacent Tihama coastal sand desert or of other sources. Fabric and size analyses of the lithic artifacts, together with spatial projections, indicate site modifications by floods. Primary modifications include (1) selective accumulation of medium‐sized lithic pieces as a result of hydraulic sorting, (2) bimodal orientation of artifacts, and (3) ripple‐like arrangement of lithics and bone/tooth fragments. The overrepresentation of teeth may also be a consequence of sorting. Although floods have distorted the original site patterning, long‐distance transport of artifacts by water can be excluded, as indicated by relatively high refitting rate, close proximity of artifacts derived from the same block of raw material, and lack of abrasion of the pieces. Therefore, the site is considered “geologically” in situ because its remobilization by water occurred shortly after human abandonment. This study also stresses that the effective preservation of a site cannot be assessed without careful taphonomic study, even in a potentially favorable depositional context such as silty alluvium.
Activation of KCNN3/SK3/KCa2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
Authors: Dolga Amalia M. , Letsche Till , Gold Maike , Doti Nunzianna , Bacher Michael , Chiamvimonvat Nipavan , Dodel Richard , Culmsee Carsten
Published: September 2012

In neurons, small‐conductance calcium‐activated potassium (KCNN/SK/KCa2) channels maintain calcium homeostasis after N‐methyl‐D‐aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/KCa2 channels in non‐neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/KCa2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N‐cyclohexyl‐N‐[2‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐6‐methyl‐4‐pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/KCa2 channels, significantly reduced LPS‐stimulated activation of microglia in a concentration‐dependent manner. The general KCNN/SK/KCa2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/KCa2 channel activation affected the changes of intracellular calcium levels, [Ca2+]i,, in microglial cells. Our data show that LPS‐induced elevation of [Ca2+]i was attenuated following activation of KCNN2/3/KCa2.2/KCa2.3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/KCa2 channel subtypes to identify which particular channel subtype mediated the observed anti‐inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/KCa2.3 channels, but not KCNN2/SK2/KCa2.2 channel inhibition, reversed the CyPPA‐effects on LPS‐induced microglial proliferation. These findings revealed that KCNN3/SK3/KCa2.3 channels can modulate the LPS‐induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/KCa2.3 channels may serve as a therapeutic target for reducing microglial activity and related inflammatory responses in the central nervous system. © 2012 Wiley Periodicals, Inc.
Complex invasion pattern of the cerebral cortex bymicroglial cells during development of the mouse embryo
Authors: Swinnen Nina , Smolders Sophie , Avila Ariel , Notelaers Kristof , Paesen Rik , Ameloot Marcel , Brône Bert , Legendre Pascal , Rigo Jean‐Michel
Published: September 2012

Microglia are the immune cells of the central nervous system. They are suspected to play important roles in adult synaptogenesis and in the development of the neuronal network. Microglial cells originate from progenitors in the yolk sac. Although it was suggested that they invade the cortex at early developmental stages in the embryo, their invasion pattern remains largely unknown. To address this issue we analyzed the pattern of cortical invasion by microglial cells in mouse embryos at the onset of neuronal cell migration using in vivo immunohistochemistry and ex vivo time‐lapse analysis of microglial cells. Microglial cells begin to invade the cortex at 11.5 days of embryonic age (E11.5). They first accumulate at the pial surface and within the lateral ventricles, after which they spread throughout the cortical wall, avoiding the cortical plate region in later embryonic ages. The invasion of the cortical parenchyma occurs in different phases. First, there is a gradual increase of microglial cells between E10.5 and E14.5. From E14.5 to E15.5 there is a rapid phase with a massive increase in microglia, followed by a slow phase again from E15.5 until E17.5. At early stages, many peripheral microglia are actively proliferating before entering the parenchyma. Remarkably, activated microglia accumulate in the choroid plexus primordium, where they are in the proximity of dying cells. Time‐lapse analysis shows that embryonic microglia are highly dynamic cells. © 2012 Wiley Periodicals, Inc.
Hippocampal involvement in retrieval of odor vs. object memories
Authors: Lehn Hanne , Kjønigsen Lisa J. , Kjelvik Grete , Håberg Asta K.
Published: September 2012

The aim of this study was to investigate the role of the human hippocampus in episodic retrieval of odors, in comparison with episodic retrieval of visual objects. Subjects encoded a set of unique odors and objects, and retrieval was tested the next day during functional magnetic resonance imaging (fMRI). Subjects were shown the names of old (studied) and new (unstudied) odors and objects, and asked to indicate which of these stimuli had been presented the previous day. The results showed that brain activation was weaker and more restricted during retrieval of odors than during retrieval of objects, which possibly reflects a general visual dominance effect. Yet, retrieval of odors and objects yielded overlapping clusters of activation the bilateral hippocampi, and the left‐sided activation was specifically increased during successful retrieval (hits > correct rejections) in both modalities. Moreover, retrieval of odors uniquely activated olfactory cortical regions, likely to reflect cortical reinstatement of sensory details. Our fMRI study is the first to make a direct comparison between olfactory and visual episodic memory, and the results provide clear evidence for modality‐independent functions of the hippocampus. © 2012 Wiley Periodicals, Inc.
Introduction of a high‐throughput double‐stent animal model for the evaluation of biodegradable vascular stents
Authors: Borinski Mauricio , Flege Christian , Schreiber Fabian , Krott Nicole , Gries Thomas , Liehn Elisa , Blindt Rüdiger , Marx Nikolaus , Vogt Felix
Published: September 2012

Current stent system efficacy for the treatment of coronary artery disease is hampered by in‐stent restenosis (ISR) rates of up to 20% in certain high‐risk settings and by the risk of stent thrombosis, which is characterized by a high mortality rate. In theory, biodegradable vascular devices exhibit crucial advantages. Most absorbable implant materials are based on poly‐L‐lactic acid (PLLA) owing to its mechanical properties; however, PLLA might induce an inflammatory reaction in the vessel wall. Evaluation of biodegradable implant efficacy includes a long‐term examination of tissue response; therefore, a simplein vivotool for thorough biocompatibility and biodegradation evaluation would facilitate future stent system development. Rats have been used for the study ofin vivodegradation processes, and stent implantation into the abdominal aorta of rats is a proven model for stent evaluation. Here, we report the transformation of the porcine double‐stent animal model into the high‐throughput rat abdominal aorta model. As genetic manipulation of rats was introduced recently, this novel method presents a powerful tool for futurein vivobiodegradable candidate stent biocompatibility and biodegradation characterization in a reliable simple model of coronary ISR. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Mathematical modeling of cross‐linking monomer elution from resin‐based dental composites
Authors: Manojlovic Dragica , Radisic Marina , Lausevic Mila , Zivkovic Slavoljub , Miletic Vesna
Published: September 2012

Elution of potentially toxic substances, including monomers, from resin‐based dental composites may affect the biocompatibility of these materials in clinical conditions. In addition to the amounts of eluted monomers, mathematical modeling of elution kinetics reveals composite restorations as potential chronic sources of leachable monomers. The aim of this work was to experimentally quantify elution of main cross‐linking monomers from four commercial composites and offer a mathematical model of elution kinetics. Composite samples (n = 7 per group) of Filtek Supreme XT (3M ESPE), Tetric EvoCeram (Ivoclar Vivadent), Admira (Voco), and Filtek Z250 (3M ESPE) were prepared in 2‐mm thick Teflon moulds and cured with halogen or light‐emitting diode light. Monomer elution in ethanol and water was analyzed using high‐performance liquid chromatography up to 28 days postimmersion. The mathematical model was expressed as a sum of two exponential regression functions representing the first‐order kinetics law. Elution kinetics in all cases followed the same mathematical model though differences in rate constants as well as the extent of monomer elution were material‐, LCU‐, medium‐dependent. The proposed mechanisms of elution indicate fast elution from surface and subsurface layers and up to 100 times slower monomer extraction from the bulk polymer. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 61–67, 2013.
Physical plugging does not account for attenuation of capillary leakage by hydroxyethyl starch 130/0.4: A synthetic gel layer model
Authors: Tatara Tsuneo , Itani Motoi , Sugi Takashi , Fujita Kimihiko
Published: September 2012

Hydroxyethyl starch (HES) solutions, widely used plasma substitutes, reportedly attenuate capillary leakage via physical plugging of capillary defects. We investigated how 2% HES solutions of different molecular weights (HES70: 70 kDa, HES130: 130 kDa, HES200: 200 kDa, and HES670: 670 kDa) affect dye release from polyacrylamide gels (PAGs) as a model of endothelial glycocalyx. We assessed dye release from 4% PAG with varying concentrations of albumin [0, 1, 2, 4, and 8% (w/v)] by measuring the change in dye absorbance (ΔAbs) at 5 h for each HES solution. For PAG containing no albumin, ΔAbs for HES130 was 30% lower than that for HES70 and HES200, and 50% lower than that for HES670. At concentrations of 1–8% albumin, ΔAbs at 5 h with HES70, HES130, and HES200 solutions were almost half that with the HES670 solution, but no significant differences were noted in ΔAbs at 5 h among HES70, HES130, and HES200 solutions. The inhibition of dye release by HES670 is likely due to the hindering effect of HES molecules partitioned into gel pores. However, a unique property of HES130, including the heavy hydroxyethylation at the C2 position, may promote specific interactions with PAG and thereby inhibit solute release. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 85–90, 2013.
Preliminary investigation of crosslinked chitosan sponges for tailorable drug delivery and infection control
Authors: Parker Ashley C. , Jennings Jessica A. , Bumgardner Joel D. , Courtney Harry S. , Lindner Ernö , Haggard Warren O.
Published: September 2012

Local versus systemic antibiotic delivery may be an effective strategy for treating musculoskeletal infections, especially when antibiotic‐resistant bacteria are present. Lyophilized uncrosslinked, genipin crosslinked, and genipin crosslinked with poly(N‐isopropylacrylamide) (PNIPAM) chitosan sponges were analyzed for theirin vitrodegradation rate, chemical crosslinking, antibiotic uptake, elution, biologic activity, and cytotoxicity. These evaluations were pursued to determine if crosslinking with genipin could be used to create a tailorable point of care loaded sponge for local infection control. Crosslinking the chitosan sponges decreased degradation in phosphate‐buffered saline from 4.48 ± 2.28 wt % remaining of the uncrosslinked sponges to 78.82 ± 1.15 and 73.87 ± 1.27 wt % remaining at week 1 for the genipin and PNIPAM/genipin crosslinked sponges, respectively. The PNIPAM/genipin crosslinked sponges exhibited the most sustained release of biologically active antibiotics, with an average antibiotic release 63% higher than uncrosslinked and 37% higher than genipin crosslinked sponges, after 96 h. No significant cytotoxic effects from sponges or eluates were exhibited with NIH 3T3 fibroblasts. These preliminary results indicate that genipin crosslinked chitosan sponges, with or without PNIPAM, have potential as local delivery systems for adjunctive therapy for infection control, especially when longer degradation periods and higher antibiotic elutions are desired. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 110–123, 2013.
Mycobacterium wolinskyi Infection Confirmed by rpoB Gene Sequencing
Authors: Jeong Ji Hun , Seo Yiel‐Hea , Kim Kyung‐Hee , Ahn Jeong‐Yeal , Park Pil‐Hwan , Park Young‐Kil
Published: September 2012

Identification of rapidly growing mycobacteria (RGM) is problematic because there are many taxonomic changes. 16S rRNA gene is commonly used to identify Mycobacterium species, but alternative gene targets have been introduced for more accurate identification. We report a rare case of a prosthetic knee infection due to Mycobacterium wolinskyi. The isolate was not identified by 16S rRNA gene sequencing alone and substantially confirmed by rpoB gene sequencing. The identification was delayed because our laboratory did not routinely identify RGM to the species level. Simultaneous sequencing of both 16S rRNA and rpoB genes will allow rapid and accurate identification of M. wolinskyi isolates. J. Clin. Lab. Anal. 26:325‐327, 2012. © 2012 Wiley Periodicals, Inc.
Clinical Relevance of Antibodies to Cardiolipin in Patients with Chronic Hepatitis C
Authors: Himoto Takashi , Yoneyama Hirohito , Kurokohchi Kazutaka , Mori Hirohito , Inukai Michio , Masugata Hisashi , Goda Fuminori , Haba Reiji , Watanabe Seishiro , Senda Shoich , Masaki Tsutomu
Published: September 2012

The significance of antibodies to cardiolipin (anti‐CL) remains uncertain in patients with chronic hepatitis C (CH‐C). The main purpose of this study was to elucidate the clinical characteristics of patients with CH‐C seropositive for anti‐CL. The prevalence of anti‐CL and clinical parameters associated with anti‐CL in those patients were examined. Six of the 45 (13%) patients with CH‐C had anti‐CL. However, none of these six CH‐C patients fulfilled the criteria for antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels in CH‐C patients with anti‐CL were significantly higher than those in CH‐C patients without anti‐CL. Serum triglyceride levels positively correlated with serum ApoB levels. CH‐C patients with anti‐CL had significantly more progressive hepatic fibrosis than those without anti‐CL. The degree of 8‐hydroxy 2′‐deoxyguanosine (8‐OHdG) expression in the liver tissue was more severe in CH‐C patients with anti‐CL than in those without it. However, the emergence of anti‐CL in CH‐C patients was independent of insulin resistance, hepatic steatosis, and iron overload. These findings suggest that the emergence of anti‐CL is associated with oxidative stress and that CH‐C patients seropositive for anti‐CL have clinical characteristics of hypertriglyceridemia, which derives from the facilitation of ApoB synthesis, and progressive hepatic fibrosis. J. Clin. Lab. Anal. 26:342‐348, 2012. © 2012 Wiley Periodicals, Inc.
Alterations of Dendritic Cell Subsets and Th1/Th2 Cytokines in the Peripheral Circulation of Patients With Superficial Transitional Cell Carcinoma of the Bladder
Authors: Lang Feng , Linlin Ma , Ye Tian , Yuhai Zhang
Published: September 2012

Background

Dendritic cells (DCs) and cytokines play an important role in the tumor growth and recurrence.

Methods

Sixty‐six patients with superficial transitional cell carcinoma of the bladder (STCCB) and 38 healthy controls were studied to investigate the percentages of DC subsets, monocyte‐derived DC (MoDC) function, and alterations of Th1 and Th2 cytokines. MoDCs were generated and three‐color flow cytometry was used for determining the phenotype of MoDCs and DC subsets. The ability to stimulate autologous T cells was tested in mixed leukocyte reaction (MLR). The levels of various cytokines were measured using commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit.

Results

The myeloid DC (mDC) counts, MoDC surface molecular expression, and stimulatory capacity to T cells were impaired in STCCB patients than in controls. The percentage of mDC and the expression of CD80, CD83, and CD86 were lower in patients showing recurrence. The serum levels of IL‐2 and IFN‐γ were found to be significantly lower while IL‐4, IL‐6, and IL‐10 were significantly higher in STCCB patients than in controls. IL‐6 was found to be significantly higher in recurrent patients.

Conclusion

The impairment of mDC counts and MoDC function with imbalance of Th1/Th2 cytokines was closely associated with proliferation and recurrence of STCCB. J. Clin. Lab. Anal. 26:365‐371, 2012. © 2012 Wiley Periodicals, Inc.
Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR
Authors: Castagnet Stéphanie , Blasco Hélène , Vourc'h Patrick , Benz‐De‐Bretagne Isabelle , Veyrat‐Durebex Charlotte , Barbet Christelle , Alnajjar Azmi , Ribourtout Bénédicte , Buchler Matthias , Halimi Jean‐Michel , Andres Christian R.
Published: September 2012

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.