bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant methylation of the PTCH1 gene promoter region in aberrant crypt foci
Authors: Peng Liang , Hu Jingjing , Li Shujun , Wang Zhongqiu , Xia Bingqing , Jiang Bo , Li Bingsheng , Zhang Yu , Wang Jing , Wang Xinying
Published: September 2012

Patched homolog 1 (PTCH1) is a known tumor suppressor that regulates the Hedgehog (Hh) pathway and has been implicated in tumorigenesis. The role of PTCH1 in colon carcinogenesis, however, is controversial. The aim of the present study was to investigate epigenetic modifications of PTCH1 in aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancer (CRC). Using laser‐capture microdissection (LCM), a pure population of ACF epithelial cells was isolated and studied. The inherent protein expression levels of SHH, PTCH1, SMO and GLI1 were assessed by immunohistochemistry for 405 ACF, including 54 dysplastic ACF (d‐ACF) and 351 non‐dysplastic ACF (n‐ACF). The mRNA levels and methylation status of PTCH1 were also determined in 54 d‐ACF and 96 n‐ACF. Our data showed that the expression of SHH, SMO and GLI1 was significantly up‐regulated in d‐ACF, compared to n‐ACF. Also, the mRNA and protein levels of PTCH1 were lower in d‐ACF than n‐ACF. Using MSP or MS‐HRM, PTCH1 methylation was present in 64.8% (35/54) or 63.3% (34/54), respectively, of d‐ACF and 19.8% (19/96) or 22.9% (11/48), respectively, of n‐ACF. PTCH1 methylation was more frequent in d‐ACF than n‐ACF (p < 0.001) and was associated with PTCH1 mRNA levels (r = 0.358, p < 0.01). There was a statistically significant correlation between PTCH1 methylation status and the prevalence of colorectal neoplasms. In conclusion, this study suggests that aberrant methylation of the PTCH1 promoter may be an early, initiating event of colon carcinogenesis.
Expanding Role of Mineralocorticoid Receptor Antagonists in the Treatment of Heart Failure
Authors: Talatinian Alidz , Chow Sheryl L. , Heywood J. Thomas
Published: September 2012

Despite numerous pharmacologic and nonpharmacologic treatment strategies, heart failure remains a complex, progressive disorder with significant morbidity and mortality. Angiotensin‐converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and β‐blockers have been used as routine treatment options for heart failure for the majority of patients with left ventricular systolic dysfunction who tolerate these agents. Mineralocorticoid receptor antagonists (MRAs) have also demonstrated significant benefits in the treatment of heart failure, which include a reduction in sudden cardiac death and ventricular remodeling; however, these agents have not been recommended for most patients with heart failure. In the most recent American College of Cardiology Foundation and American Heart Association guidelines, MRAs are recommended for patients with New York Heart Association class III or IV symptoms or previous acute myocardial infarction, provided an absence of contraindications or risk factors for developing hyperkalemia. Based on more recent evidence, it is likely that future recommendations and guidelines will further expand the use of MRAs to patients with mild heart failure as well. These agents have the potential to be recommended nearly as universally as ACE inhibitors and β‐blockers because of the potential to reduce mortality and hospital admissions for heart failure. The risk of hyperkalemia should be carefully assessed when using these drugs; nonetheless, new strategies being developed may reduce the occurrence of hyperkalemia as well.
Drug Dosing Based on Weight and Body Surface Area: Mathematical Assumptions and Limitations in Obese Adults
Authors: Pai Manjunath P.
Published: September 2012

The average weight of adults in the United States has increased by 25 pounds (11 kg) over the past 50 years, with a marginal change in height. Drugs are generally dosed according to one of three approaches: fixed dosing, weight‐based dosing, or body surface area–based dosing. Dosing based on body weight or body surface area assumes that drug pharmacokinetic parameters increase in proportion with increasing body size. In contrast, dosing drugs on a fixed basis assumes that drug pharmacokinetic parameters do not increase with body size. Unfortunately, early stages of clinical drug development tend to include adults within a narrow range of body size. This study population does not reflect the current U.S. population distribution and does not permit evaluation of the correct relationship between body size and drug clearance. As a consequence, a weight‐based or body surface area–based dosing regimen defined during drug development may not be applicable to U.S. patient populations. These dosing strategies are more likely to result in drug overexposure (weight‐based approach) or underexposure (body surface area–based approach) among obese patients. Alternate weight descriptors such as ideal body weight, adjusted body weight, fat‐free weight, and lean body weight are used to prevent drug overexposure with weight‐based dosing, but their benefits and limitations must be understood. Reappraisal of the drug dosing paradigm is needed in this era of rising obesity; however, until drug‐specific reviews can be performed, clinical studies must include patients at the extremes of the weight continuum to ensure applicable dose extrapolation for body size.
Practical Considerations for the Pharmacotherapy of Pulmonary Arterial Hypertension
Authors: Bishop Bryan M. , Mauro Vincent F. , Khouri Samer J.
Published: September 2012

Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin‐1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin‐1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in‐depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.
Effect of Therapeutic Doses of Acetaminophen (up to 4 g/day) on Serum Alanine Aminotransferase Levels in Subjects Consuming Ethanol: Systematic Review and Meta‐analysis of Randomized Controlled Trials
Authors: Rumack Barry , Heard Kennon , Green Jody , Albert Donald , Bucher‐Bartelson Becki , Bodmer Michael , Sivilotti Marco L. A. , Dart Richard C.
Published: September 2012

Study Objective

To quantify the effect of therapeutic doses of acetaminophen on serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol.

Design

Systematic review of six randomized placebo‐controlled trials, of which five were included in a meta‐analysis.

Subjects

Subjects included in the meta‐analysis were those who consumed ethanol and received acetaminophen in doses up to 4 g/day (551 subjects) or placebo (350 subjects).

Measurements and Main Results

A comprehensive literature search of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases and the Cochrane Central Register of Controlled Trials was performed to identify randomized, placebo‐controlled trials that enrolled subjects who consumed ethanol, received acetaminophen in therapeutic doses up to 4 g/day, and had serum ALT level measurements. A total of 184 articles were identified; six articles met all criteria. Five of the six articles reported ALT levels on study day 4 for both groups of subjects who received acetaminophen or placebo. Thus, for the meta‐analysis, we used the primary outcome of mean change in serum ALT level from baseline to day 4 in the acetaminophen groups compared with the placebo groups. We found that the difference in mean change from baseline ALT levels between the acetaminophen and placebo groups on day 4 was 0.0 U/L (95% confidence interval −0.2–0.1 U/L). There were no reports of liver dysfunction, liver failure, or death in any of the trials.

Conclusion

In randomized, placebo‐controlled trials of subjects who consumed ethanol, no elevation of ALT level on study day 4 was noted when subjects ingested up to 4 g/day of acetaminophen.
Effects of transmyocardial jet revascularization with chitosan hydrogel on channel patency and angiogenesis in canine infarcted hearts
Authors: Zhou Dayan , Xiong Lu , Wu Qi , Guo Rui , Zhou Zhiyi , Zhu Que , Jiang Yonghong , Huang Jing
Published: September 2012

The purpose of this study was to investigate whether transmyocardial jet revascularization (TMJR) with chitosan scaffolds retains channel patency and enhances angiogenesis after acute myocardial infarction (AMI) in a canine model. A total of 32 canines were randomly divided into four groups: myocardial infarction (MI), normal saline (NS), chitosan hydrogel (CH), and chitosan plus growth factor (CH + GF) groups. TMJR was performed surgically using a needle‐free injector from the epicardium of canines in the NS, CH, and CH + GF groups; channels were filled with NS, CH, and CH + GF, respectively. After 6 weeks, the patency of the channels and angiogenesis around the channels were assessed by hematoxylin–eosin staining, immunohistochemistry, and Masson's trichrome staining. Results suggest that the channels in the CH and CH + GF groups may retain patency with luminal endothelization. Moreover, the vessel densities of the NS, CH, and CH + GF groups were significantly higher than that of the MI group, and that of the CH + GF group was the highest (p < 0.05). This study suggests that TMJR with chitosan scaffolds may help retain transmyocardial channel patency and enhance angiogenesis after AMI in canines. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Aptamers: A promising tool for cancer imaging, diagnosis, and therapy
Authors: Liu KuanCan , Lin BaoShun , Lan XiaoPeng
Published: September 2012

Aptamers are a group of molecules, which can specifically bind, track, and inhibit target molecules, comprising DNA aptamers, RNA aptamers, and peptide aptamers. So far, there are much progress about developing novel aptamers and their expansile applications. This prospect systematically introduces the composition and technological evolution of aptamers, and then focuses on the application of aptamers in cancer diagnosis, imaging, and therapy. Following this, we discuss the potential to harness aptamers in discovering the biomarker of stem cells, which is favorable for us to study the normal developmental or abnormal pathological process of tissue and to deliver drugs into target cells or tissues in the future. J. Cell. Biochem. 114: 250–255, 2013. © 2012 Wiley Periodicals, Inc.
Secreted phosphoprotein‐24 kDa (Spp24) attenuates BMP‐2‐stimulated Smad 1/5 phosphorylation and alkaline phosphatase induction and was purified in a protective complex with alpha2‐Macroglobulins From Serum
Authors: Zhao Ke‐Wei , Murray Samuel S. , Murray Elsa J. Brochmann
Published: September 2012

Secreted phosphoprotein‐24 kDa (Spp24) binds cytokines of the bone morphogenetic protein/transforming growth factor‐β (BMP/TGFβ) superfamily and is one of the most abundant serum phosphoproteins synthesized by the liver. Little is known about how Spp24 binding affects BMP signal transduction and osteoblastic differentiation or how this labile protein is transported from the liver to remote tissues, such as bone. When Spp24 was administered to W‐20‐17 mesenchymal stem cells with rhBMP‐2, short‐term Smad1/5 phosphorylation was inhibited, intermediate‐term alkaline phosphatase (ALP) induction was blunted, and long‐term mineralization was unaffected. This supports the hypothesis that Spp24 proteolysis restricts the duration of its regulatory effects, but offers no insight into how Spp24 is transported intact from the liver to bone. When Spp24 was immunopurified from serum and subjected to native PAGE and Western blotting, a high molecular weight band of >500 kDa was found. Under reducing SDS–PAGE, a 24 kDa band corresponding to monomeric Spp24 was liberated, suggesting that Spp24 is bound to a complex linked by disulfide bonds. However, such a complex cannot be disrupted by 60 mM EDTA under non‐reducing condition or in purification buffers containing 600 mM NaCl and 0.1% Tween‐20 at pH 2.7–8.5. LC–MS/MS analysis of affinity‐purified, non‐reducing SDS–PAGE separated, and trypsin digested bands showed that the Spp24 was present in a complex with three α2‐macroglobulins (α2‐macroglobulin [α2M], pregnancy zone protein [PZP] and complement C3 [C3]), as well as ceruloplasmin and the protease inhibitor anti‐thrombin III (Serpin C1), which may protect Spp24 from proteolysis. J. Cell. Biochem. 114: 378–387, 2013. © 2012 Wiley Periodicals, Inc.
Mesenchymal stem cells protect cigarette smoke‐damaged lung and pulmonary function partly via VEGF–VEGF receptors
Authors: Guan Xiao‐Jun , Song Lin , Han Feng‐Feng , Cui Zhi‐Lei , Chen Xi , Guo Xue‐Jun , Xu Wei‐Guo
Published: September 2012

Progressive pulmonary inflammation and emphysema have been implicated in the progression of chronic obstructive pulmonary disease (COPD), while current pharmacological treatments are not effective. Transplantation of bone marrow mesenchymal stem cells (MSCs) has been identified as one such possible strategy for treatment of lung diseases including acute lung injury (ALI) and pulmonary fibrosis. However, their role in COPD still requires further investigation. The aim of this study is to test the effect of administration of rat MSCs (rMSCs) on emphysema and pulmonary function. To accomplish this study, the rats were exposed to cigarette smoke (CS) for 11 weeks, followed by administration of rMSCs into the lungs. Here we show that rMSCs infusion mediates a down‐regulation of pro‐inflammatory mediators (TNF‐α, IL‐1β, MCP‐1, and IL‐6) and proteases (MMP9 and MMP12) in lung, an up‐regulation of vascular endothelial growth factor (VEGF), VEGF receptor 2, and transforming growth factor (TGFβ‐1), while reducing pulmonary cell apoptosis. More importantly, rMSCs administration improves emphysema and destructive pulmonary function induced by CS exposure. In vitro co‐culture system study of human umbilical endothelial vein cells (EA.hy926) and human MSCs (hMSCs) provides the evidence that hMSCs mediates an anti‐apoptosis effect, which partly depends on an up‐regulation of VEGF. These findings suggest that MSCs have a therapeutic potential in emphysematous rats by suppressing the inflammatory response, excessive protease expression, and cell apoptosis, as well as up‐regulating VEGF, VEGF receptor 2, and TGFβ‐1. J. Cell. Biochem. 114: 323–335, 2013. © 2012 Wiley Periodicals, Inc.
Abnormality of maternal‐to‐embryonic transition contributes to MEHP‐induced mouse 2‐cell block
Authors: Chu Da‐Peng , Tian Shi , Qi Lu , Hao Chan‐Juan , Xia Hong‐Fei , Ma Xu
Published: September 2012

Mono (2‐ethylhexyl) phthalate (MEHP), an environmental contaminant, is known to cause many serious diseases, especially in reproductive system. However, little is known about the effect of MEHP on preimplantation embryo development. In this study, we found that the development of mouse 2‐cell embryo was blocked by 10−3 M MEHP. A significant increase in the level of reactive oxygen species (ROS) was observed in arrested 2‐cell embryo following 10−3 M MEHP treatment for 24 h. However, antioxidants, catalase (CAT), and superoxide dismutase (SOD), reduced intracellular ROS and protected MEHP‐exposed embryos from death but failed to return the arrested embryos. Further experiments demonstrated that the level of apoptosis was not altered in live arrested 2‐cell embryo and increased in dead arrested 2‐cell embryo after MEHP treatment, which implied that ROS and apoptosis were not related with 2‐cell block. During analysis of the indicators of embryonic genome activation (EGA) initiation (Hsc70, MuERV‐L, Hsp70.1, eIF‐1A, and Zscan4) and maternal‐effect genes (OCT4 and SOX2), we found that MEHP treatment could significantly decline Hsc70, MuERV‐L mRNA level and SOX2 protein level, and markedly enhance Hsp70.1, eIF‐1A, Zscan4 mRNA level, and OCT4 protein level at 2‐cell to 4‐cell stage. Supplementation of CAT and SOD did not reverse the expression tendency of EGA related genes. Collectively, this study demonstrates for the first time that MEHP‐induced 2‐cell block is mediated by the failure of EGA onset and maternal‐effect genes, not oxidative stress and apoptosis. J. Cell. Physiol. 228: 753–763, 2013. © 2012 Wiley Periodicals, Inc.
Human mesenchymal stem cells: A bank perspective on the isolation, characterization and potential of alternative sources for the regeneration of musculoskeletal tissues
Authors: Moroni Lorenzo , Fornasari Pier Maria
Published: September 2012

The continuous discovery of human mesenchymal stem cells (hMSCs) in different tissues is stirring up a tremendous interest as a cell source for regenerative medicine therapies. Historically, hMSCs have been always considered a sub‐population of mononuclear cells present in the bone marrow (BM). Although BM‐hMSCs are still nowadays considered as the most promising mesenchymal stem cell population to reach the clinics due to their capacity to differentiate into multiple tissues, hMSCs derived from other adult and fetal tissues have also demonstrated to possess similar differentiation capacities. Furthermore, different reports have highlighted a higher recurrence of hMSCs in some of these tissues as compared to BM. This offer a fascinating panorama for cell banking, since the creation of a stem cell factory could be envisioned where hMSCs are stocked and used for ad hoc clinical applications. In this review, we summarize the main findings and state of the art in hMSCs isolation, characterization, and differentiation from alternative tissue sources and we attempt to compare their potency for musculoskeletal regeneration. J. Cell. Physiol. 228: 680–687, 2013. © 2012 Wiley Periodicals, Inc.
Histogenesis of the unique morphology of proboscidean ivory
Authors: Virág Attila
Published: September 2012

The chequered pattern (often called Schreger pattern), which can be seen by unaided eye on transverse profiles of several proboscidean tusks and which can be emphasized by the spreading pattern of the cracks or by mineral discoloration, is an autapomorph feature of the clade Elephantoidea. The pattern differs among proboscidean taxa; therefore, it allows the coarse differentiation of elephants, mammoths, and some other basal groups. Such identification methods could facilitate efforts concerned with protection of the remaining elephant populations through ivory trade restrictions, since the tooth dentine from extinct Mammuthusprimigenius and from extant Loxodontaafricana and Elephasmaximus are the most common raw materials of the ivory carvings. The aim of this study was to show the internal structure of proboscidean ivory and to revise the existing theories on the aforementioned pattern of the elephantoids with reflections on the events which lead to the development of this microstructure. Thin sections and natural crack surfaces with various orientations of M.primigenius, Elephasantiquus, Prodeinotherium, and Deinotherium tusk fragments were used to produce a three‐dimensional model which explains the features on all profiles. The “phase shift” model is introduced, which assumes a sinusoid undulation of the dentinal tubules in radial profiles in the case of elephantoids. The model was confirmed by photomicrographs, scanning electron microscopic images, interpretation of natural crack surfaces, and radial displacement analysis of the dentinal tubules. The latter proved that the adjacent waves are not in the same phase. Several new nondestructive distinguishing methods are described here on the basis of the correlation between some microscopic and macroscopic features related to the Schreger pattern. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.
NDVI, temperature and precipitation changes and their relationships with different vegetation types during 1998–2007 in Inner Mongolia, China
Authors: Chuai X. W. , Huang X. J. , Wang W. J. , Bao G.
Published: September 2012

Based on vegetation maps of Inner Mongolia, SPOT‐VEGETATION normalized difference vegetation index (NDVI) data, and temperature and precipitation data from 118 meteorological stations, this study analysed changes in NDVI, temperature and precipitation, and performed correlation analyses of NDVI, temperature and precipitation for eight different vegetation types during the growing seasons (April–October) of the period 1998–2007 in Inner Mongolia, China. We also investigated seasonal correlations and lag‐time effects, and our results indicated that for different vegetation types, NDVI changes during 1998–2007 showed great variation. NDVI correlated quite differently with temperature and precipitation, with obvious seasonal differences. Lag‐time effects also varied among vegetation types and seasons. On the whole, Inner Mongolia is becoming warmer, and drier for most regions, and ecological pressure in Inner Mongolia is increasing, and our focus on such issues is therefore important. Copyright © 2012 Royal Meteorological Society
Determination of cyflumetofen residue in water, soil, and fruits by modified quick, easy, cheap, effective, rugged, and safe method coupled to gas chromatography/tandem mass spectrometry
Authors: Li Minmin , Liu Xingang , Dong Fengshou , Xu Jun , Qin Dongmei , Zheng Yongquan
Published: September 2012

A new, highly sensitive, and selective method was developed for the determination of the cyflumetofen residue in water, soil, and fruits by using gas chromatography quadruple mass spectrometry. The target compound was extracted using acetonitrile and then cleaned up using dispersive solid‐phase extraction with primary and secondary amine and graphitized carbon black, and optionally by a freezing‐out cleanup step. The matrix‐matched standards gave satisfactory recoveries and relative standard deviation values in different matrices at three fortified levels (0.05, 0.5, and 1.0 mg kg−1). The overall average recoveries for this method in water, soil, and all fruits matrix at three fortified levels ranged from 76.3 to 101.5% with relative standard deviations in the range of 1.2–11.8% (n = 5). The calculated limits of detection and quantification were typically below 0.005 and 0.015 μg kg−1, which were much lower than the maximum residue levels established by Japanese Positive List. This study provides a theoretical basis for China to draw up maximum residue level and analytical method for cyflumetofen acaricide in different fruits.
Rapid separation of beryllium and lanthanide derivatives by capillary gas chromatography
Authors: Harvey Scott D. , Lucke Richard B. , Douglas Matt
Published: September 2012

Previous studies describe derivatization of metal ions followed by analysis using gas chromatography, usually on packed columns. In many of these studies, stable and volatile derivatives were formed using fluorinated β‐diketonate reagents. This paper extends previous work by investigating separations of the derivatives on small‐diameter capillary gas chromatography columns and exploring on‐fiber, solid‐phase microextraction derivatization techniques for beryllium. The β‐diketonate used for these studies was 1,1,1,2,2,6,6,7,7,7‐decafluoro‐3,5‐heptanedione. Derivatization of lanthanides also required addition of a neutral donor, dibutyl sulfoxide, in addition to 1,1,1,2,2,6,6,7,7,7‐decafluoro‐3,5‐heptanedione. Unoptimized separations on a 100‐μm i.d. capillary column proved capable of rapid separations (within 15 min) of lanthanide derivatives that are adjacent to one another in the periodic table. Full‐scan mass spectra were obtained from derivatives containing 5 ng of each lanthanide. Studies also developed a simple on‐fiber solid‐phase microextraction derivatization of beryllium. Beryllium could be analyzed in the presence of other alkali earth elements (Ba(II) and Sr(II)) without interference. Extension of the general approach was demonstrated for several additional elements (i.e. Cu(II), Cr(III), and Ga(III)).
Delipidating effect of resveratrol metabolites in 3T3‐L1 adipocytes
Authors: Lasa Arrate , Churruca Itziar , Eseberri Itziar , Andrés‐Lacueva Cristina , Portillo María P.
Published: September 2012

Scope

Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue.

Methods and results

3T3‐L1 maturing pre‐adipocytes were treated from day 0 to day 8 of differentiation and mature adipocytes for 24 h on day 12 with 1, 10, or 25 μM of resveratrol or its metabolites. Triacylglycerols were assessed by spectrophotometry and gene expression by real time RT‐PCR. Resveratrol, trans‐resveratrol‐4′‐O‐glucuronide and trans‐resveratrol‐3‐O‐sulfate reduced triacylglycerol content in maturing pre‐adipocytes at 25 μM. In mature adipocytes, both resveratrol and its glucuronide metabolites, though not sulfate metabolite, reduced triacylglycerol content, although resveratrol was more effective than them. Resveratrol and the three metabolites reduced C/EBPβ mRNA levels. Trans‐resveratrol‐3‐O‐sulfate also reduced C/EBP‐α, peroxisome proliferator‐activated receptor γ (PPAR‐γ), and lipoprotein lipase (LPL) expression. In mature adipocytes, resveratrol increased ATGL, CPT‐1, deacetylase sirtuin 1 (SIRT‐1), and PGC1‐α expression. Trans‐resveratrol‐3‐O‐glucuronide reduced mRNA levels of FASN and increased those of SIRT‐1. Trans‐resveratrol‐4′‐O‐glucuronide increased HSL and SIRT‐1 mRNA levels. Trans‐resveratrol‐3‐O‐sulfate did not change gene expression.

Conclusion

The present study shows for the first time the delipidating effect of (i) resveratrol metabolites in maturing pre‐adipocytes and (ii) glucuronide metabolites in mature adipocytes. This suggests that both resveratrol and resveratrol metabolites may be involved in the anti‐obesity effect of this polyphenol.
Forced vertical and horizontal movements of a rectangular rigid foundation on a transversely isotropic half‐space
Authors: Eskandari‐Ghadi Morteza , Ardeshir‐Behrestaghi Azizollah , Pak Ronald Y. S. , Karimi Mostafa , Momeni‐Badeleh Masoud
Published: September 2012

An analytical investigation of a half‐space containing transversely isotropic material under forced vertical and horizontal displacements applied on a rectangular rigid foundation is presented in this paper. With the goal of a rigorous solution to the shape‐ and rigidity‐ induced singular mixed boundary value problem, the formulation employs scalar potential representation, the Fourier expansion and the Hankel integral transforms method to obtain the surface arbitrary point‐load solution in cylindrical coordinate system. The obtained Green's functions are rewritten in rectangular coordinate system, allowing the response of the half‐space because of an arbitrary distributed load on a rectangular surface area be given in terms of a double integral. The numerical evaluations of stresses are done with the use of an element, which is singular at the edge and the corner of the rectangle. Upon the imposition of the rigidity displacement boundary condition for a rigid foundation and the use of a set of two‐dimensional adaptive‐gradient elements, which can capture the singular behavior in the contact stress effectively, a set of new numerical results are presented to illustrate the effect of transverse isotropy on the foundation response. Copyright © 2012 John Wiley & Sons, Ltd.
Attitudes to prenatal diagnosis and termination of pregnancy for 30 conditions among women in Saudi Arabia and the UK
Authors: Alsulaiman Ayman , Hewison Jenny , Abu‐Amero Khaled K. , Ahmed Shenaz , Green Josephine M. , Hirst Janet
Published: September 2012

Objective

The aim of this research was to compare attitudes between women from different cultural and/or religious backgrounds toward prenatal diagnosis (PND) and termination of pregnancy (TOP) for 30 different conditions.

Methods

A questionnaire examining parents' attitudes toward PND and TOP for 30 different conditions was completed by 100 Saudi, 222 UK‐White, and 198 UK‐Pakistani women. Comparison of overall attitudes with PND and TOP between groups was carried out, and a total score reflecting attitudes was obtained.

Results

In general, there were positive attitudes toward PND among the three groups surveyed. The attitudes of Saudi and UK‐Pakistani women toward PND were more favorable than UK‐White women. Overall, acceptance of TOP was lower than for PND. For the majority of conditions, acceptance of TOP was highest in Saudi women and lowest in UK‐Pakistani women.

Conclusion

Attitudes toward TOP were significantly different between the three groups and may be influenced by cultural and/or religious factors. Availability of social services, genetic counseling, and rehabilitation centers may also influence attitude toward PND and TOP. © 2012 John Wiley & Sons, Ltd.
A study on the mismatch effect due to the use of different photovoltaic modules classes in large‐scale solar parks
Authors: Massi Pavan Alessandro , Mellit Adel , De Pieri Davide , Lughi Vanni
Published: September 2012

In this paper, a study on the mismatch effect due to the use of different photovoltaic (PV) modules classes in large‐scale solar parks is presented. For this purpose, a new model for simulating current–voltage and power–voltage characteristics is introduced. The model is then applied for calculating mismatch losses in a number of case studies for a PV plant built in Bari, southern Italy. First, in order to test the effectiveness of the model, this is applied to homogeneous strings and field showing that the mismatch losses are zero. Subsequently, the use of inhomogeneous strings (i.e. made of modules belonging to different power classes) is investigated. Finally, the behaviour of 1 MWp homogeneous and inhomogeneous PV fields is investigated, again with a focus on the mismatch effect. The operational conditions have been introduced starting from the definition of European efficiency. The use of standard test conditions can in fact lead to gross approximations because mismatch losses depend, as well as, on PV module characteristics, electrical connections and electrical architecture, also on the location of the PV system. The results presented in this work can be used both by PV system designers for carrying out yield calculations, and by operation and maintenance personnel for substituting modules during operation without compromising the productivity of the plant. Copyright © 2012 John Wiley & Sons, Ltd.
Psychopathy and deception detection
Authors: Martin Krystle , Leach Amy‐May
Published: September 2012

Researchers have found that most people have difficulty detecting deception; however, certain individuals are able to consistently detect deception above the level of chance. This study examined whether psychopathic traits are related to deception detection. Undergraduate participants (n = 117) indicated whether individuals in video clips were lying or telling the truth and completed a measure of psychopathy. Overall, participants' performance was significantly greater than chance. Scores on the psychopathy measure were unrelated to participants' performance and their confidence on the lie detection task. Possible explanations for the findings are briefly discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Mechanisms of interaction between luteolin and the catalytic zinc ion in matrix metalloproteinases: a computational study
Authors: Zhang Ji , Li Hui , Fan Yi‐Ran , Zhou Xia
Published: September 2012

Many experimental studies have found that flavonoids including luteolin can inhibit the activities of matrix metalloproteinases (MMPs), but the related theoretical studies are rather lacking. In this paper, we perform PM6 quantum chemistry calculations together with modeling of ligand‐water exchange reactions to investigate the mechanisms of interaction between luteolin and catalytic zinc ion in MMPs. The calculations show that the electron transfer from the luteolin molecule to the catalytic zinc ion in MMPs occurs when the catalytic zinc ion coordinates with the O atoms of substituent groups at various positions of A, B, and C rings of luteolin molecule. It is found that the more the number of the electron transfer from one coordinating O atom of substituent groups of luteolin molecule to the catalytic zinc ion, the stronger the coordinating ability between them. We further find that comparing with the O atoms of hydroxy groups at 5‐, 7‐, 3′‐, and 4′‐positions of luteolin molecule, the coordinating ability for the O atom of carbonyl group at its 4‐position with the catalytic zinc ion is the strongest, which indicates that when luteolin inhibits MMPs activity, the catalytic zinc ion should coordinate with the carbonyl group at 4‐position of luteolin molecule, rather than the hydroxy groups at its other positions, in agreement with the relevant experimental results reported in previous literature. This paper may be helpful for designing the new MMPs inhibitors having higher biological activities by carrying out the structural modifications of luteolin molecule. Copyright © 2012 John Wiley & Sons, Ltd.
Bronchoscopy and airway management in patients with mucopolysaccharidoses (MPS)
Authors: Muhlebach Marianne S. , Shaffer Christopher B. , Georges Linda , Abode Kathy , Muenzer Joseph
Published: September 2012

Introduction

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders characterized by tissue deposition of glycosaminoglycans (GAG). Their musculoskeletal abnormalities and the GAG storage in the airway result in increased risk for patients undergoing anesthesia. This study evaluates a multi‐disciplinary airway management approach and reports upper and lower airway findings of flexible bronchoscopy performed during these procedures.

Methods

This is a retrospective study over 10 years evaluating approaches to and outcomes of airway management and bronchoscopic findings in this patient group.

Results

Thirty‐one patients underwent a total of 105 anesthetic events of which 74 involved multiple surgical services. The majority of patients were either MPS I (n = 9) or MPS II (n = 19). The median age was 8.6 years (range 1.1–24 years). Airway management by anesthesiologists alone occurred in 31 cases including natural airway (n = 7), perilaryngeal airway (n = 7), oral or nasal intubation (n = 7) or tracheostomy (n = 6) and emergent fiberoptic intubation in four cases. In 74 of the procedures, flexible bronchoscopy was performed which included fiberoptic intubation in 22 cases. Post‐operative complications occurred in eight cases mostly when prolonged airway instrumentation had occurred. The most frequent findings on bronchoscopy were GAG deposits/adenoid hypertrophy in 72%, laryngomalacia in 31% and lower airway deposits and/or tracheobronchomalacia in 46% of procedures. Deposits of GAG were seen in patients as young as 4 years of age.

Conclusion

Our experience demonstrates that a multidisciplinary approach and combined surgeries in MPS provides for safe airway management and allows diagnostic assessments for further patient care without added risks. Significant, multi‐factorial airway compromise may occur already in early childhood including upper and lower airway GAG deposits. Pediatr Pulmonol. 2013; 48:601–607. © 2012 Wiley Periodicals, Inc.
Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: IV. colistimethate sodium
Authors: Young David C. , Zobell Jeffery T. , Waters C. Dustin , Ampofo Krow , Stockmann Chris , Sherwin Catherine M.T. , Spigarelli Michael G.
Published: September 2012

Patients with cystic fibrosis (CF) often experience acute pulmonary exacerbations (APE) and may be treated with a wide variety of intravenous antibiotics. The aim of this review is to provide an evidence‐based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing the intravenous (IV) polymixin antibiotic colistimethate sodium (CMS) in the treatment of APE and to identify areas where further study is warranted. Currently, there is not an international standard on the labeling of CMS products. As a result, this has lead to confusion in the interpretation of the literature with respect to efficacy, tolerance, and optimal dosing strategy. The dosing ranges of IV CMS from the literature are 5.3–12.9 mg/kg/day, maximum 480 mg per day for 60 kg patient (Colomycin® injection‐European product) and 8–21.3 mg/kg/day, maximum 800 mg per day for 60 kg patient (Coly‐Mycin M® parenteral‐US product).The literature supports a CMS dose of 8 mg/kg/day divided every 8 hr (maximum 480 mg/day) for the treatment of APE secondary to Pseudomonas aeruginosa. The maximum recommended CMS dose of 480 mg/day is less than is recommended by the FDA‐approved and CFF dosing guidelines but in agreement with UK CF Trust Antibiotic Working Group recommendations. There is debate over the frequency of CMS administration (once daily vs. thrice‐daily) and its impact on resistance and clinical efficacy. Further study is needed to determine the tolerability and efficacy of extended‐interval dosing of CMS in the treatment of APE. Pediatr Pulmonol. 2013; 48:1–7. © 2012 Wiley Periodicals, Inc.
Successful use of plasmapheresis for granulomatosis with polyangiitis presenting as diffuse alveolar hemorrhage
Authors: Haupt Mark E. , Pires‐Ervoes John , Brannen Melissa L. , Klein‐Gitelman Marisa S. , Prestridge Adrienne L. , Nevin Mary A.
Published: September 2012

Diffuse alveolar hemorrhage (DAH) is uncommon in pediatric patients and is a rare presenting sign of granulomatosis with polyangiitis (GPA). We present the case a 14‐year‐old girl who presented with respiratory failure secondary to DAH as the initial presenting sign of GPA. Her clinical course improved after initiation of plasmapheresis therapy and she is now in clinical remission. Pediatr Pulmonol. 2013; 48:614–616. © 2012 Wiley Periodicals, Inc.
Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. cephalosporins and penicillins
Authors: Zobell Jeffery T. , Waters C. Dustin , Young David C. , Stockmann Chris , Ampofo Krow , Sherwin Catherine M.T. , Spigarelli Michael G.
Published: September 2012

Acute pulmonary exacerbations (APE) are well‐described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti‐pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence‐based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti‐pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin–tazobactam and ticarcillin–clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200–400 mg/kg/day divided every 6–8 hr, maximum 8–12 g/day, and 150–200 mg/kg/day divided every 6–8 hr, up to 6–8 g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350–600 mg/kg/day divided every 4 hr, maximum 18–24 g/day of piperacillin component, and 400–750 mg/kg/day divided every 6 hr, up to 24–30 g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA‐approved doses of ceftazidime, cefepime, and ticarcillin–clavulanate in APE. The usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to treatment‐related adverse effects. Further understanding of these adverse effects in CF patients is needed. Pediatr Pulmonol. 2013; 48:107–122. © 2012 Wiley Periodicals, Inc.
On‐plate deposition of oxidized proteins to facilitate protein footprinting studies by radical probe mass spectrometry
Authors: Maleknia Simin D. , Downard Kevin M.
Published: September 2012

The on‐plate deposition of oxidized proteins is described to advance footprinting applications by radical probe mass spectrometry (RP‐MS). An electrospray ionization (ESI) needle assembly mounted vertically over a 384‐target matrix‐assisted laser desorption/ionization (MALDI) plate enabled the limited oxidation of proteins as they were released in the charged droplets ahead of their deposition on the plate. This method combined with on‐plate proteolytic digestion protocols expedites the analysis of proteins oxidized by RP‐MS, and avoids the need to collect and reconstitute samples prior to analysis by MALDI mass spectrometry. Oxidation of peptides from solutions in water as well as an ammonium bicarbonate solution was investigated to test the optimal conditions required for on‐plate oxidation of proteins. These comprised of peptides with a wide range of reactive amino acids including Phe, Tyr, Pro, His, Leu, Met and Lys that were previously shown to oxidize in both electrospray discharge and synchrotron radiolysis based footprinting experiments. The on‐plate deposition of lysozyme oxidized at electrospray needle voltages of 6 and 9 kV were carried out to demonstrate conditions suitable for footprinting experiments as well as those that induce the onset of protein damage. Copyright © 2012 John Wiley & Sons, Ltd.
The use of group sequential designs with common competing risks tests
Authors: Logan Brent R. , Zhang Mei‐Jie
Published: September 2012

Clinical trials are often performed using a group sequential design in order to allow investigators to review the accumulating data sequentially and possibly terminate the trial early for efficacy or futility. Standard methods for comparing survival distributions have been shown under varying levels of generality to follow an independent increments structure. In the presence of competing risks, where the occurrence of one type of event precludes the occurrence of another type of event, researchers may be interested in inference on the cumulative incidence function, which describes the probability of experiencing a particular event by a given time. This manuscript shows that two commonly used tests for comparing cumulative incidence functions, a pointwise comparison at a single point, and Gray's test, also follow the independent increments structure when used in a group sequential setting. A simulation study confirms the theoretical derivations even for modest trial sample sizes. We used two examples of clinical trials in hematopoietic cell transplantation to illustrate the techniques. Copyright © 2012 John Wiley & Sons, Ltd.
Susceptibility of Young and Adult Rats to the Oral Toxicity of Titanium Dioxide Nanoparticles
Authors: Wang Yun , Chen Zhangjian , Ba Te , Pu Ji , Chen Tian , Song Yanshuang , Gu Yongen , Qian Qin , Xu Yingying , Xiang Kun , Wang Haifang , Jia Guang
Published: September 2012

Titanium dioxide nanoparticles (TiO2 NPs) have potential applications as food additives, but concerns persist about their safety. Children are identified as having the highest exposure and may face the greatest health risks. However, the toxicological sensitivity of TiO2 NPs in different ages is not clear. Here, a comparative toxicity study of TiO2 NPs in 3‐week (youth) and 8‐week (adult) old Sprague‐Dawley rats is reported following oral exposure at doses of 0, 10, 50, 200 mg kg−1 body weight per day for 30 days. The organ mass and histology, blood biochemistry and redox state, intestinal function, and biodistribution of NPs are characterized. The results show that TiO2 NPs induce different toxic effects on young and adult rats. The liver edema, heart injuries and non‐allergic mast cell activation in stomach tissues are found in young rats. On the other hand, only slight injury in the liver and kidney and decreased intestinal permeability and molybdenum contents are found in adult rats. Furthermore, TiO2 NP exposure can provoke reductive stress (i.e., increased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios) in plasmas through enhancing the glucose and GSH levels in young rats or reducing the glutathione peroxidase (GSH‐Px) acitivity and GSSG levels in adult rats. These results suggest that different ages may require different biomarkers for identifying and monitoring oral toxicity of nanoparticles.
Optimum design of tower structures using Firefly Algorithm
Authors: Talatahari Siamak , Gandomi Amir Hossein , Yun Gun Jin
Published: September 2012

The Firefly Algorithm (FA) as a recent new meta‐heuristic optimization algorithm is developed for determining optimum design of tower shaped structures. The FA mimics the social behavior of fireflies, which communicate, search for pray and find mates using bioluminescence with varied flashing patterns. In this paper, an adaptive FA is presented that utilizes the feasible‐based method to handle constraints. This method is effective in improving the convergence and also suitable for expensive optimization tasks such as large‐scale structures. Three tower structures are selected to evaluate the performance of the algorithm. The results are better than the other results proposed in the literature and confirm the validity of the proposed algorithm. Copyright © 2012 John Wiley & Sons, Ltd.
Literacy Research That Informs Practice
Authors: Barone Diane M. , Mallette Marla H.
Published: September 2012

This Editorial provides an overview about previous research that has been documented to inform practice. We moved from this research base and asked a wider audience to respond to what books or articles they believed made a difference to classroom practice. Each of the authors whose books were mentioned was asked to write an article for The Reading Teacher. One of these articles will appear in each issue of this volume year.
Complex Text or Frustration‐Level Text: Using Shared Reading to Bridge the Difference
Authors: Dougherty Stahl Katherine A.
Published: September 2012

Challenging texts can be made accessible to students by increasing the level of instructional scaffolding. This article describes evidence‐based models of shared reading that support reading development across the elementary years. Shared Reading Experience (Holdaway, 1982), Fluency‐Oriented Reading Instruction (Stahl & Heubach, 2005), think‐alouds, and high‐level discussion enable students to successfully read texts that might be considered frustration level if relying upon traditional criteria for determining difficulty.
Just Breathe, and Keep Going
Authors: Callura Mary Ellen
Published: September 2012

View From the Chalkboard essays share readers’ reflections on teaching experiences, advice for new teachers, and perspectives on current issues.