bluuebunny/crossref_metadata_2025 huggingface dataset:
IntraLase Femtosecond Laser vs Mechanical Microkeratomes in LASIK for Myopia: A Systematic Review and Meta-analysis
Authors: Chen Shihao , Feng Yifan , Stojanovic Aleksandar , Jankov Mirko R. , Wang Qinmei
Published: January 2012

PURPOSE:

To evaluate the safety, efficacy, and predictability of IntraLase (Abbott Medical Optics) femtosecond laser–assisted compared to microkeratome-assisted myopic LASIK.

METHODS:

A comprehensive literature search of Cochrane Library, PubMed, and EMBASE was conducted to identify relevant trials comparing LASIK with IntraLase femtosecond laser to LASIK with microkeratomes for the correction of myopia. Meta-analyses were performed on the primary outcomes (loss of ≥2 lines of corrected distance visual acuity [CDVA], uncorrected distance visual acuity [UDVA] 20/20 or better, manifest refraction spherical equivalent [MRSE] within ±0.50 diopters [D], final refractive SE, and astigmatism), and secondary outcomes (flap thickness predictability, changes in higher order aberrations [HOAs], and complications).

RESULTS:

Fifteen articles describing a total of 3679 eyes were identified. No significant differences were identified between the two groups in regards to a loss of ≥2 lines of CDVA (
P
=.44), patients achieving UDVA 20/20 or better (
P
=.24), final UDVA (
P
=.12), final mean refractive SE (
P
=.74), final astigmatism (
P
=.27), or changes in HOAs. The IntraLase group had more patients who were within ±0.50 D of target refraction (
P
=.05) compared to the microkeratome group, and flap thickness was more predictable in the IntraLase group (
P
<.0001). The microkeratome group had more epithelial defects (
P
=.04), whereas the IntraLase group had more cases of diffuse lamellar keratitis (
P
=.01).

CONCLUSIONS:

According to the available data, LASIK with the IntraLase femtosecond laser offers no significant benefits over LASIK with microkeratomes in regards to safety and efficacy, but has potential advantages in predictability.
Current Thinking in Qualitative Research: Evidence-Based Practice, Moral Philosophies, and Political Struggle
Authors: Papadimitriou Christina , Magasi Susan , Frank Gelya
Published: January 2012

In this introduction to the special issue on current thinking in qualitative research and occupational therapy and science, the authors focus on the importance of rigorous qualitative research to inform occupational therapy practice. The authors chosen for this special issue reflect a “second generation of qualitative researchers” who are critical, theoretically sophisticated, methodologically productive, and politically relevant to show that working with disabled clients is political work. Three themes emerged across the articles included in this special issue: (1) recognizing and addressing social justice issues; (2) learning from clients' experiences; and (3) critically reframing occupational therapy's role. These themes can inform occupational therapy practice, research, and education to reflect a more client-centered and politically engaging approach.
AN INTERACTIVE CBIR SYSTEM BASED ON ANFIS LEARNING SCHEME FOR HUMAN BRAIN MAGNETIC RESONANCE IMAGES RETRIEVAL
Authors: Tarjoman Mana , Fatemizadeh Emad , Badie Kambiz
Published: January 2012

Content-based image retrieval (CBIR) has turned into an important and active potential research field with the advance of multimedia and imaging technology. It makes use of image features, such as color, texture and shape, to index images with minimal human intervention. A CBIR system can be used to locate medical images in large databases. In this paper we propose a CBIR system which describes the methodology for retrieving digital human brain magnetic resonance images (MRI) based on textural features and the Adaptive neuro-fuzzy inference system (ANFIS) learning to retrieve similar images from database in two categories: normal and tumoral. A fuzzy classifier has been used, because of the uncertainty in the results of classifier and capacity of learning. ANFIS is a good candidate for our categorization problem. Our proposed CBIR system can locate a query image in the category of normal or tumoral images in the online retrieval part. Finally, using a relevance feedback, we improve the effectiveness of our retrieval system. This research uses the knowledge of the CBIR approach to the application of medical decision support and discrimination between the normal and abnormal medical images based on features. We present and compare the results of the proposed method with the CBIR systems used in recent works. The experimental results indicate that the proposed method is reliable and has high image retrieval efficiency compared with the previous works.
PHYSIOLOGICAL SIGNAL ANALYSIS FOR COGNITIVE STATE ESTIMATION
Authors: Ahmad Mohiuddin , Islam Atiqul , Khan Munia T. T. , Rashid M. A. , Tunku Mansur T. M. N.
Published: January 2012

The purpose of this paper is to identify inconsistency in human physiological signals based on cognitive states by measuring and analyzing bio-signals. In this paper, the cognitive states are estimated using physiological signal analysis. The parameters are electrocardiogram (ECG), electromyogram (EMG), electroencephalogram (EEG) and blood pressure (BP). The signals have been collected using BIOPAC system in which the subjects were induced to undergo the specific sequence of the cognitive state. For getting physiological signals during different conditions, we utilized power point slide show, video clips and question answer method which elicits mental reactions from the subjects. Data is taken before and after four tasks that encompassed the motor action (MA), thought (TH), memory related (MR) and emotion (EM). These measured values are analyzed using BIOPAC Acknowledge software. It was found that the motor action and thought states have effects on BP while MR and EM state mainly affect the ECG measurement. The decibel value and frequency found for EM state in ECG are minimum compared to relaxed state (RS) condition. Similarly, the maximum frequency and dB value is found for MR state. No significant variation was seen for MA and TH states. Thus it was decided that the MR and EM states mainly affect the ECG measurement. For BP the value increases in MA state and decreases in TH state. The MA state mainly affects the EMG signal while other states have no significant changes. The EEG mainly detects the signal of task performed by the specific brain region where the electrodes are placed. In EEG analysis, the electrodes are placed in occipital lobe region which gives mainly the variation in alpha amplitude of EEG with eyes closed and eyes opened. Alpha wave amplitudes vary with the subjects attention to mental tasks performed with eyes closed.
TRAIL+ Human Plasmacytoid Dendritic Cells Kill Tumor Cells In Vitro: Mechanisms of Imiquimod- and IFN-α–Mediated Antitumor Reactivity
Authors: Kalb Madeleine L. , Glaser Astrid , Stary Georg , Koszik Frieder , Stingl Georg
Published: January 2012

Dendritic cells (DCs) not only exhibit the unique capacity to evoke primary immune responses, but may also acquire TLR-triggered cytotoxic activity. We and others have previously shown that TLR7/8- and TLR9-stimulated plasmacytoid DCs (pDCs) isolated from human peripheral blood express the effector molecule TRAIL. The exact mechanisms through which pDCs acquire and elicit their cytotoxic activity are still not clear. We now show that in the absence of costimulators, TRAIL induction on pDCs occurs with agonists to intracellular TLRs only and is accompanied by a phenotypic as well as functional maturation, as evidenced by a comparatively superior MLR stimulatory capacity. pDCs acquired TRAIL in an IFN-α/β–dependent fashion and, notably, TRAIL expression on pDCs could be induced by IFN-α stimulation alone. At a functional level, both TLR7/8- (imiquimod [IMQ]) and TLR9-stimulated (CpG2216) pDCs lysed Jurkat T cells in a TRAIL- and cell contact-dependent fashion. More importantly, IFN-α–activated pDCs acquired similar cytotoxic properties, independent of TLR stimulation and maturation. Both IMQ- and IFN-α–activated pDCs could also lyse certain melanoma cell lines in a TRAIL-dependent fashion. Interestingly, suboptimal doses of IMQ and IFN-α exhibited synergistic action, leading to optimal TRAIL expression and melanoma cell lysis by pDCs. Our data imply that tumor immunity in patients receiving adjuvant IMQ and/or IFN-α may involve the active participation of cytotoxic pDCs.
The causes of flow regime shifts in the semi-arid Hailiutu River, Northwest China
Authors: Yang Z. , Zhou Y. , Wenninger J. , Uhlenbrook S.
Published: January 2012

Abstract. Identifying the causes (climate vs. human activities) for hydrological variability is a major challenge in hydrology. This paper examines the flow regime shifts, changes in the climatic variables such as precipitation, evaporation, temperature, and crop area in the semi-arid Hailiutu catchment in the middle section of the Yellow River by performing several statistical analyses. The Pettitt test, cumulative sum charts (CUSUM), regime shift index (RSI) method, and harmonic analysis were carried out on annual, monthly, and daily discharges. Four major shifts in the flow regime have been detected in 1968, 1986, 1992 and 2001. Characteristics of the flow regime were analyzed in the five periods: 1957–1967, 1968–1985, 1986–1991, 1992–2000, and 2001–2007. From 1957 to 1967, the flow regime reflects quasi natural conditions of the high variability and larger amplitude of 6 months periodic fluctuations. The river peak flow was reduced by the construction of two reservoirs in the period 1968–1985. In the period of 1986–1991, the river discharge further decreased due to the combined influence of river diversions and increase of groundwater extractions for irrigation. In the fourth period of 1992–2000, the river discharge reached lowest flow and variation in corresponding to a large increase in crop area. The flow regime recovered, but not yet to natural status in the fifth period of 2001–2007. Climatic factors are found not likely responsible for the changes in the flow regime, but the changes in the flow regime are corresponding well to historical land use policy changes.
Evaluation of Central Vein Sizes in Patients with Autogenous Hemodialysis Fistulas
Authors: Yau Jaron A. , Rajan Dheeraj K.
Published: January 2012

Purpose

To quantify diameters of central vein segments in patients with autogenous hemodialysis fistulas.

Materials and Methods

A retrospective review of patients within the last year who underwent arterial venous fistula assessment identified 218 patients. Of these, 32 also had computed tomography (CT) of the thorax performed from which venous sizes could be ascertained. Measurements in the axial plane (diameter) of the central veins were obtained from calibrated DICOM images. Additional demographic information including age, sex, and location of the fistula were also acquired to determine whether there was any correlation of these factors with the vein diameters. Variables were compared using the unpaired t test.

Results

There were 21 and 11 patients with left-sided and right-sided fistulas, respectively, with a mean age of 61.1 years. There was no statistically significant difference (P<.05) found between the diameter when comparing men to women (P=.93 to .22) or patient ages less than or greater than 70 years old (P=.95 to .11). The only statistically significant difference observed was when the fistula was located in the left arm, with the left axillary vein being larger than the right (11.4 ± 0.6 and 8.4 ± 0.6 respectively P=.003). The remaining vessels showed no statistically significant difference in size with respect to the fistula location (P=.75 to .07).

Conclusions

The left axillary vein is significantly larger in patients who have a fistula located in the left arm compared to the right. Central vein sizes measured by CT correlate with sizes measured angiographically in prior retrospective studies.
A Substituting Meaning for the Equals Sign in Arithmetic Notating Tasks
Authors: Jones Ian , Pratt Dave
Published: January 2012

We present 3 studies trialing arithmetic tasks that support both substitutive and basic relational meanings for the equals sign. The duality of meanings enabled children to engage meaningfully and purposefully with the structural properties of arithmetic statements in novel ways. In particular, they observed and exploited distinctive transformational effects when using different statement types to make substitutions of notation. We show how the initial version of the task emphasized the substitutive meaning but not the basic relational meaning, and an adapted version required both meanings of the equals sign to be flexibly coordinated. We found that some, but not all, children were successful at the adapted task and were able to connect making substitutions of notation with their existing mental calculation strategies.
“She's Always Been the Smart One. I've Always Been the Dumb One”: Identities in the Mathematics Classroom
Authors: Bishop Jessica Pierson
Published: January 2012

The moment-to-moment dynamics of student discourse plays a large role in students' enacted mathematics identities. Discourse analysis was used to describe meaningful discursive patterns in the interactions of 2 students in a 7th-grade, technology-based, curricular unit (SimCalc MathWorlds®) and to show how mathematics identities are enacted at the microlevel. Frameworks were theoretically and empirically connected to identity to characterize the participants' relative positioning and the structural patterns in their discourse (e.g., who talks, who initiates sequences, whose ideas are taken up and publicly recognized). Data indicated that students' peer-to-peer discourse patterns explained the enactment of differing mathematics identities within the same local context. Thus, the ways people talk and interact are powerful influences on who they are, and can become, with respect to mathematics.
Ferrocene conjugates with mannose: synthesis and influence of ferrocene aglycon on mannose‐mediated adhesion of Escherichia coli
Authors: Kovačević Monika , Barišić Lidija , Ribić Rosana , Peroković Vesna Petrović , Tomić Srđanka , Rapić Vladimir
Published: January 2012

Bacterial adhesion, mediated through interaction of bacterial lectins with carbohydrate structures presented on the surface of the host cells, is a prerequisite for infection. Anti‐adhesion therapy, based on the inhibition of lectins by suitable carbohydrates, has been considered as a weapon for the combat of microbial diseases. Structural alteration of aglycon portions of mannose derivatives strongly influences their inhibitory potency toward type 1 fimbriated Escherichia coli. Thus several conjugates of mannose‐containing ferrocene aglycon moieties were synthesized and tested. The novel ferrocene conjugates 10, 12 and 14 were obtained by esterification of O‐mannosylated propionic acid 1 with ferrocene alcohols R‐Fn‐(CH2)n‐OH (Fn = 1,1'‐ferrocenylene; 2, n = 1, R = COOMe; 7, n = 1, R = NHBoc; 8, n = 2, R = H) in the presence of Boc2O/DMAP with subsequent debenzylation of the intermediate O‐protected esters. Performed hemagglutination inhibitory tests showed that the examined bioorganometallics exhibit better inhibitory activity than known inhibitor methyl α‐d‐mannoside. Thus ferrocene–mannose conjugate 14 with the dimethylene spacer between ferrocene core and chiral linker displayed the best inhibitory efficiency. Copyright © 2012 John Wiley & Sons, Ltd.
Immersing undergraduate students in the research experience
Authors: Wang Jack T. H. , Schembri Mark A. , Ramakrishna Mathitha , Sagulenko Evgeny , Fuerst John A.
Published: January 2012

Molecular cloning skills are an essential component of biological research, yet students often do not receive this training during their undergraduate studies. This can be attributed to the complexities of the cloning process, which may require many weeks of progressive design and experimentation. To address this issue, we incorporated an immersive 12‐week undergraduate research experience into an upper‐level molecular microbiology course. Students completed two 6‐week modules where the entire molecular cloning process was carried out for two sets of novel genes implicated in distinct biological processes, microbial cell division and bacterial pathogenesis. The first module trained students in molecular cloning experimental skills, and the second facilitated the application of these skills within a new biological context. Students designed and optimized primers targeted against specific genes, andthen PCR amplified, purified, and quantified the DNA of their gene of interest. Using a variety of strategies, students inserted these genes into expression plasmids to produce GFP and His‐tag fusion proteins; this was tested through restriction digestion or colony PCR and verified by gel electrophoresis. At the end of each module, students were assessed on comprehension of biological concepts, professional laboratory note‐keeping and scientific communication, and proficiencies in experimental procedures. The recombinant plasmids produced by the students directly contributed to ongoing research projects, and the molecular cloning skills learnt are applicable to many career and study options in molecular biology. Overall, this research experience trained students in professional molecular biology and microbiology practice and engages them in producing real‐world research outcomes.
Beyond vascularization: aerobic fitness is associated with N‐acetylaspartate and working memory
Authors: Erickson Kirk I. , Weinstein Andrea M. , Sutton Bradley P. , Prakash Ruchika Shaurya , Voss Michelle W. , Chaddock Laura , Szabo Amanda N. , Mailey Emily L. , White Siobhan M. , Wojcicki Thomas R. , McAuley Edward , Kramer Arthur F.
Published: January 2012

Aerobic exercise is a promising form of prevention for cognitive decline; however, little is known about the molecular mechanisms by which exercise and fitness impacts the human brain. Several studies have postulated that increased regional brain volume and function are associated with aerobic fitness because of increased vascularization rather than increased neural tissue per se. We tested this position by examining the relationship between cardiorespiratory fitness and N‐acetylaspartate (NAA) levels in the right frontal cortex using magnetic resonance spectroscopy. NAA is a nervous system specific metabolite found predominantly in cell bodies of neurons. We reasoned that if aerobic fitness was predominantly influencing the vasculature of the brain, then NAA levels should not vary as a function of aerobic fitness. However, if aerobic fitness influences the number or viability of neurons, then higher aerobic fitness levels might be associated with greater concentrations of NAA. We examined NAA levels, aerobic fitness, and cognitive performance in 137 older adults without cognitive impairment. Consistent with the latter hypothesis, we found that higher aerobic fitness levels offset an age‐related decline in NAA. Furthermore, NAA mediated an association between fitness and backward digit span performance, suggesting that neuronal viability as measured by NAA is important in understanding fitness‐related cognitive enhancement. Since NAA is found exclusively in neural tissue, our results indicate that the effect of fitness on the human brain extends beyond vascularization; aerobic fitness is associated with neuronal viability in the frontal cortex of older adults.
Fistula between right coronary artery vein graft and right atrium as an immediate complication of percutaneous coronary intervention
Authors: El Hosieny Adel , Hui William
Published: January 2012

Fistula between saphenous vein graft (SVG) and a cardiac chamber or structure is a rare complication after coronary artery bypass grafting (CABG). We report the first case of a fistula between SVG and the right atrium (RA) as an immediate complication after a percutaneous coronary intervention (PCI) in an 86‐year‐old female. She presented with inferior ST‐elevation myocardial infarction (STEMI) and was treated with thrombolytic therapy in a peripheral hospital, which was unsuccessful. PCI to SVG to the right coronary (RCA) was complicated by a fistula to RA. Cardiac magnetic resonance (CMR) confirmed the site of the fistula and also presence of a significant arteriovenous (AV) shunt. Reversal of anticoagulation had no effect on fistula closure. Therefore, a covered stent was deployed for closure of the fistula to avoid long‐term complications of the significant AV shunt. In summary, the diagnosis and appropriate management of this rare complication is challenging, but excellent result can be achieved by the use of appropriate percutaneous techniques. © 2012 Wiley Periodicals, Inc.
Studies of extraction of methylene blue from synthetic waste water using liquid emulsion membrane technology
Authors: Gadade Pradip Rajabhau , Sardare Mamta Devrao , Chavan Abhijit Ramchandra
Published: January 2012

A comprehensive study pertaining to liquid emulsion membrane (LEM) extraction process of methylene blue from wastewater is presented. The liquid membrane is made of an emulsifying agent (Monumal 80) with various organic diluents. Surfactant (5 wt%) (Monumal 80) and kerosene gave good extraction. Important variables affecting LEM permeation process include stability of membrane, contact time of extraction, strip phase concentration, treat ratio (strip phase: organic phase), stirring speed, feed phase concentration were systematically studied for percentage of extraction by LEM. Kerosene as diluent gave 99.57% extraction with NaOH as strip phase. © 2012 Canadian Society for Chemical Engineering
Chiral Mercaptoacetamides Display Enantioselective Inhibition of Histone Deacetylase 6 and Exhibit Neuroprotection in Cortical Neuron Models of Oxidative Stress
Authors: Kalin Jay H. , Zhang Hankun , Gaudrel‐Grosay Sophie , Vistoli Giulio , Kozikowski Alan P.
Published: January 2012

Mercaptoacetamide‐based ligands have been designed as a new class of histone deacetylase (HDAC) inhibitors for possible use in the treatment of neurodegenerative diseases. The thiol group of these compounds provides a key binding element for interaction with the catalytic zinc ion, and thus differs from the more typically employed hydroxamic acid based zinc binding groups. Herein we disclose the chemistry and biology of some substituted mercaptoacetamides with the intention of increasing HDAC6 isoform selectivity while maintaining potency similar to their hydroxamic acid analogues. The introduction of a stereocenter α to the thiol group was found to have a considerable impact on HDAC inhibitor potency. These new compounds were also profiled for their therapeutic potential in an in vitro model of stress‐induced neuronal injury and were found to act as nontoxic neuroprotective agents.
Summary of ‘Different antibiotic treatments for group A streptococcal pharyngitis (Review)’
Authors: Editorial Office Evidence‐Based Child Health
Published: January 2012

This is a summary of Cochrane review, published in this issue of EBCH, first published as: van Driel ML, De Sutter AIM, Keber N, Habraken H, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis (Review). Cochrane Database of Systematic Reviews 2010, Issue 10. Art.No.: CD004406. DOI: 10.1002/14651858.CD004406.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Different antibiotic treatments for group A streptococcal pharyngitis (Review)’
Authors: Baltimore Robert S.
Published: January 2012

This is a commentary of Cochrane review, published in this issue of EBCH, first published as: van Driel ML, De Sutter AIM, Keber N, Habraken H, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis (Review). Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No.:CD004406. DOI: 10.1002/14651858.CD004406.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Adjusting the pH of lidocaine for reducing pain on injection’
Authors: Kilbaugh Todd J.
Published: January 2012

This is a commentary of Cochrane review, published in this issue of EBCH, first published as: Cepeda MS, Tzortzopoulou A, Thackrey M, Hudcova J, Arora Gandhi P, Schumann R. Adjusting the pH of lidocaine for reducing pain on injection. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD006581. DOI:10.1002/14651858.CD006581.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Care delivery and self‐management strategies for children with epilepsy’
Authors: Editorial Office Evidence‐Based Child Health
Published: January 2012

This is a summary of Cochrane review, published in this issue of EBCH, first published as: Lindsay B, Bradley PM. Care delivery and self‐management strategies for children with epilepsy. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD006245. DOI: 10.1002/14651858.CD006245.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentaries on ‘Nonsteroidal anti‐inflammatory drugs and tonsillectomy perioperative bleeding in paediatric tonsillectomy’
Authors: Blakley Brian W. , Tomkinson Alun , Owens David , Jones Rhys M.
Published: January 2012

These are commentaries of Cochrane review, published in this issue of EBCH, first published as: Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti‐inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database of Systematic Reviews Commentary2005, Issue 2. Art. No.: CD003591. DOI: 10.1002/14651858.CD003591.pub2

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Single‐Strand Molecular Wheels and Coordination Polymers in Copper(II) Benzoate Chemistry by the Employment of α‐Benzoin Oxime and Azides: Synthesis, Structures, and Magnetic Characterization
Authors: Stamatatos Theocharis C. , Vlahopoulou Gina , Raptopoulou Catherine P. , Psycharis Vassilis , Escuer Albert , Christou George , Perlepes Spyros P.
Published: January 2012

The use of α‐benzoin oxime (bzoxH2) in copper(II) benzoate chemistry, in the absence or presence of ancillary azido ligands, is reported. The reaction of Cu(O2CPh)2·2H2O with one equivalent of bzoxH2 in N,N‐dimethylformamide (DMF) affords the decanuclear complex [Cu10(bzox)10(DMF)4] (1) in good yield. Dissolution of 1 in CH2Cl2 leads to the subsequent isolation of the solvent‐free complex [Cu10(bzox)10] (2) in moderate yields. Complexes 1 and 2 are isostructural and possess a loop or single‐strand molecular wheel topology. The bzox2– dianions behave as η1:η1:η2:μ3 ligands, which give rise to an overall [Cu10(μ‐ONR)10(μ‐OR′)10] core. Both 1 and 2 stack to form nanotubular columns with beautiful supramolecular architectures. The reaction of Cu(O2CPh)2·2H2O with bzoxH2 and NaN3 in a 1:1:1 molar ratio in MeOH gives the bzoxH2‐free complex [Cu(N3)(O2CPh)(MeOH)]n (3), which is a 1D chain. The CuII atoms in 3 are linked by a single, end‐on N3– group, a syn,syn‐η1:η1:μ PhCO2– ion, and an oxygen atom from the bridging MeOH ligand. The 1D chains are hydrogen bonded into 2D sheets through Nazide···H(OMeOH) interactions. Variable‐temperature, solid‐state direct‐current magnetic studies were carried out on 1–3. The data for 1 and 2 indicate very strong antiferromagnetic exchange interactions and a S = 0 ground state, which is expected for even‐membered loop arrays of CuII atoms. In contrast, 3 exhibits ferromagnetic exchange interactions; the data were fitted to the appropriate equation derived from the Hamiltonian H = –JΣ(Si·Si+1), which includes a zJ′ interchain interaction term. The best‐fit parameters were J = +49.6(4) cm–1, g = 2.067(3), and zJ′ = 2.3(1) K. The combined results demonstrate the ligating flexibility of both the bzoxH2 and azido groups and their usefulness in the synthesis of polynuclear CuII clusters and coordination polymers.
Quantitative experimental determination of primer–dimer formation risk by free‐solution conjugate electrophoresis
Authors: Desmarais Samantha M. , Leitner Thomas , Barron Annelise E.
Published: January 2012

DNA barcodes are short, unique ssDNA primers that “mark” individual biomolecules. To gain better understanding of biophysical parameters constraining primer–dimer formation between primers that incorporate barcode sequences, we have developed a capillary electrophoresis method that utilizes drag‐tag‐DNA conjugates to quantify dimerization risk between primer‐barcode pairs. Results obtained with this unique free‐solution conjugate electrophoresis approach are useful as quantitatively precise input data to parameterize computation models of dimerization risk. A set of fluorescently labeled, model primer‐barcode conjugates were designed with complementary regions of differing lengths to quantify heterodimerization as a function of temperature. Primer–dimer cases comprised two 30‐mer primers, one of which was covalently conjugated to a lab‐made, chemically synthesized poly‐N‐methoxyethylglycine drag‐tag, which reduced electrophoretic mobility of ssDNA to distinguish it from ds primer–dimers. The drag‐tags also provided a shift in mobility for the dsDNA species, which allowed us to quantitate primer–dimer formation. In the experimental studies, pairs of oligonucleotide primer barcodes with fully or partially complementary sequences were annealed, and then separated by free‐solution conjugate CE at different temperatures, to assess effects on primer–dimer formation. When less than 30 out of 30 base‐pairs were bonded, dimerization was inversely correlated to temperature. Dimerization occurred when more than 15 consecutive base‐pairs formed, yet non‐consecutive base‐pairs did not create stable dimers even when 20 out of 30 possible base‐pairs bonded. The use of free‐solution electrophoresis in combination with a peptoid drag‐tag and different fluorophores enabled precise separation of short DNA fragments to establish a new mobility shift assay for detection of primer–dimer formation.
Effect of the cytochrome P450 2D6*10 allele on risperidone metabolism in Japanese psychiatric patients
Authors: Suzuki Yutaro , Fukui Naoki , Tsuneyama Nobuto , Watanabe Junzo , Ono Shin , Sugai Takuro , Saito Mami , Inoue Yoshimasa , Someya Toshiyuki
Published: January 2012

Objective

The sum of the serum levels of risperidone (RIS) and 9‐hydroxyrisperidone (9‐OH‐RIS), which is the active moiety serum level, could be important for estimating the clinical effects of RIS. However, there have been no consistent results reported about the relationship between cytochrome P450 (CYP) 2D6*10 allele and plasma 9‐OH‐RIS or active moiety levels. We investigated the effect of the number of CYP2D6*10 alleles on steady‐state plasma RIS, 9‐OH‐RIS, and active moiety levels in Japanese patients.

Methods

Steady‐state plasma RIS, 9‐OH‐RIS, and active moiety levels were measured in 64 patients treated with an average dosage of 4.6 mg/day.

Results

The number of CYP2D6*10 alleles significantly affected dose‐corrected plasma RIS levels (p = 0.001), and the median concentrations in ng/ml/mg were 0.94 (0 allele) vs. 1.73 (1 allele) vs. 3.05 (2 alleles). The number of CYP2D6*10 alleles did not affect plasma 9‐OH‐RIS or active moiety levels.

Conclusion

The present study shows that the number of CYP2D6*10 alleles affected plasma RIS levels but not plasma 9‐OH‐RIS and plasma active moiety levels. Because the plasma active moiety levels can influence antipsychotic effects or side effects, the genetic screening of the CYP2D6*10 allele for RIS in Asian populations may not be clinically important. Copyright © 2012 John Wiley & Sons, Ltd.
Systemic blockade of the hyaluronan receptor for endocytosis prevents lymph node metastasis of prostate cancer
Authors: Simpson Melanie A. , Weigel Janet A. , Weigel Paul H.
Published: January 2012

Tumor progression and metastasis are promoted by the remodeling of organized tissue architecture and engagement of molecular interactions that support tumor cell passage through endothelial barriers. Prostate tumor cells that secrete and turn over excessive quantities of pericellular hyaluronan (HA) exhibit accelerated growth kinetics and spontaneous lymph node metastasis in mice. The HA receptor for endocytosis (HARE) is an endocytic clearance receptor for HA in the liver that is also highly expressed in sinusoidal endothelium of lymph nodes and bone marrow, which are frequent sites of prostate cancer metastasis. In our study, we tested the hypothesis that HARE can act as an endothelial receptor for metastatic tumor cells with pericellular HA. In an orthotopic mouse model of prostate cancer, we delivered a monoclonal antibody against HARE that specifically blocks HA binding and internalization. This treatment fully blocked the formation of metastatic tumors in lymph nodes. No effects on primary tumor growth were observed and the antibody did not induce toxic outcomes in any other tissue. Our results implicate HARE for the first time in potentiation of tumor metastasis and suggest a novel mechanism by which tumor cell‐associated HA could promote tissue‐specific dissemination. “Published 2012 Wiley Periodicals, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America.”
Low values of 5‐hydroxymethylcytosine (5hmC), the “sixth base,” are associated with anaplasia in human brain tumors
Authors: Kraus Theo F.J. , Globisch Daniel , Wagner Mirko , Eigenbrod Sabina , Widmann David , Münzel Martin , Müller Markus , Pfaffeneder Toni , Hackner Benjamin , Feiden Wolfgang , Schüller Ulrich , Carell Thomas , Kretzschmar Hans A.
Published: January 2012

5‐Methylcytosine (5mC) in genomic DNA has important epigenetic functions in embryonic development and tumor biology. 5‐Hydroxymethylcytosine (5hmC) is generated from 5mC by the action of the TET (Ten‐Eleven‐Translocation) enzymes and may be an intermediate to further oxidation and finally demethylation of 5mC. We have used immunohistochemistry (IHC) and isotope‐based liquid chromatography mass spectrometry (LC‐MS) to investigate the presence and distribution of 5hmC in human brain and brain tumors. In the normal adult brain, IHC identified 61.5% 5hmC positive cells in the cortex and 32.4% 5hmC in white matter (WM) areas. In tumors, positive staining of cells ranged from 1.1% in glioblastomas (GBMs) (WHO Grade IV) to 8.9% in Grade I gliomas (pilocytic astrocytomas). In the normal adult human brain, LC‐MS also showed highest values in cortical areas (1.17% 5hmC/dG [deoxyguanosine]), in the cerebral WM we measured around 0.70% 5hmC/dG. 5hmC levels were related to tumor differentiation, ranging from lowest values of 0.078% 5hmC/dG in GBMs (WHO Grade IV) to 0.24% 5hmC/dG in WHO Grade II diffuse astrocytomas. 5hmC measurements were unrelated to 5mC values. We find that the number of 5hmC positive cells and the amount of 5hmC/dG in the genome that has been proposed to be related to pluripotency and lineage commitment in embryonic stem cells is also associated with brain tumor differentiation and anaplasia.
Evaluation of the hybrid capture 2 assay for detecting anal high‐grade dysplasia
Authors: Goldstone Stephen E. , Lowe Brian , Rothmann Thomas , Nazarenko Irina
Published: January 2012

Hybrid Capture 2 (HC2) Human Papillomavirus (HPV) DNA Test® is FDA approved and is a proven aid in detecting HPV infections of the cervix and as an aid in diagnosing, with cytology, cervical disease. A prospective feasibility study was conducted to determine if HC2 testing has utility when screening for high‐grade anal dysplasia (AIN2+). We enrolled 298 patients (45% HIV+) who had AIN2+ screening with cytology, histology and HC2 testing for two specimens: a swab into liquid‐based cytology medium and either a swab or a brush collection in specimen transport medium (STM). High‐resolution anoscopy was performed on all patients with biopsy of AIN2+ suspicious lesions. Cytology was benign (42%), atypical squamous cells of undetermined significance (30%), low‐grade squamous intraepithelial lesion (18%), high‐grade squamous intraepithelial lesion (1%), ASCUS possibly high‐grade dysplasia (1.7%) and nondiagnostic (7%) and 36% had AIN2+ histology. Sensitivity and specificity for predicting AIN2+ histology for any abnormal cytology were 77 and 52%, whereas HC2 sensitivity and specificity were 91 and 40% (p = 0.005 for sensitivity), respectively. There was no significant difference in HC2 sensitivity or specificity between brush and swab or STM and residual cells from cytology. AIN2+ was found in 20% of patients with benign cytology. Only nine AIN2+ specimens were HC2−. This prospective study indicates that HC2 may be useful when screening for anal dysplasia; however, a larger study is recommended.
Percutaneous absorption in diseased skin: an overview
Authors: Chiang Audris , Tudela Emilie , Maibach Howard I.
Published: January 2012

The stratum corneum's (SC) functions include protection from external hazardous environments, prevention of water loss and regulation of body temperature. While intact skin absorption studies are abundant, studies on compromised skin permeability are less common, although products are often used to treat affected skin. We reviewed literature on percutaneous absorption through abnormal skin models. Tape stripping is used to disrupt water barrier function. Studies demonstrated that physicochemical properties influence the stripping effect: water‐soluble drugs are more affected. Abrasion did not affect absorption as much. Freezing is commonly used to preserve skin. It does not seem to modify water absorption, but still increases the penetration of compounds. Comparatively, heating the skin consistently increased percutaneous absorption. Removing SC lipids may increase percutaneous absorption of drugs. Many organic solvents are employed to delipidize. Delipidization with chloroform–methanol increased hydrophilic compound permeability, but not lipophilic. Acetone pre‐treatment enhanced hydrophilic compound penetration. More data is needed to determine influence on highly lipophilic compound penetration. Sodium lauryl sulfate (SLS) induces irritant dermatitis and is frequently used as a model. Studies revealed that SLS increases hydrophilic compound absorption, but not lipophilic. However, skin irritation with other chemicals increases lipophilic penetration as much as hydrophilic. Animal studies show that UV exposure increases percutaneous absorption whereas human studies do not. Human studies show increased penetration in psoriatic and atopic dermatitis skin. The data summarized here begin to characterize flux alteration associated with damaged skin. Understanding the degree of alteration requires interpretation of involved conditions and the enlarging of our database to a more complete physicochemical spectrum. Copyright © 2012 John Wiley & Sons, Ltd.
Developing in vitro reporter gene assays to assess the hormone receptor activities of chemicals frequently detected in drinking water
Authors: Sun Hong , Si Chaozong , Bian Qian , Chen Xiaodong , Chen Liansheng , Wang Xinru
Published: January 2012

The present study intended to develop receptor‐mediated luciferase reporter gene assays to evaluate and compare the estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) activities of target chemicals. Di‐2‐ethylhexyl‐phthalate (DEHP), chlorpyrifos (CPF), 2,4‐dichlorophenoxyacetic acid (2,4‐D) and bisphenol A (BPA) are some of the most common contaminants in drinking water and are frequently detected in China and worldwide. The chemicals were tested at concentrations of 0.1, 1, 10 and 100 times their maximum contaminant level in drinking water. The results showed that BPA possessed various activities on ER, AR and TR. DEHP and CPF could suppress 17β‐estradiol or testosterone activity with different potencies, and DEHP possessed weaker anti‐thyroid hormone activity. 2,4‐D showed no agonist or antagonist activity against these hormone receptors, but it significantly enhanced the activity of testosterone through AR. Furthermore, the mixture of DEHP and CPF exhibited stronger ER and AR antagonist activities than each single component alone, but their combined effects were less than the expected effects based on the additive model. These results implied that the transcription activation mediated by hormone receptors was the potential endocrine‐disrupting mechanism of the test chemicals. Our study also provided useful tools for evaluation of their endocrine disrupting activity. Copyright © 2012 John Wiley & Sons, Ltd.
The inhibition of hyaluronan degradation reduced pro‐inflammatory cytokines in mouse synovial fibroblasts subjected to collagen‐induced arthritis
Authors: Campo Giuseppe M. , Avenoso Angela , D'Ascola Angela , Scuruchi Michele , Prestipino Vera , Nastasi Giancarlo , Calatroni Alberto , Campo Salvatore
Published: January 2012

Hyaluronan (HA) degradation produces small oligosaccharides that are able to increase pro‐inflammatory cytokines in rheumatoid arthritis synovial fibroblasts (RASF) by activating both CD44 and the toll‐like receptor 4 (TLR‐4). CD44 and TLR‐4 stimulation in turn activate the NF‐kB that induces the production of pro‐inflammatory cytokines. Degradation of HA occurs via two mechanisms: one exerted by reactive oxygen species (ROS) and one controlled by different enzymes in particular hyaluronidases (HYALs). We aimed to investigate the effects of inhibiting HA degradation (which prevents the formation of small HA fragments) on synovial fibroblasts obtained from normal DBA/J1 mice (NSF) and on synovial fibroblasts (RASF) obtained from mice subjected to collagen induced arthritis (CIA), both fibroblast types stimulated with tumor necrosis factor alpha (TNF‐α). TNF‐α stimulation produced high mRNA expression and the related protein production of CD44 and TLR‐4 in both NSF and RASF, and activation of NF‐kB was also found in all fibroblasts. TNF‐α also up‐regulated the inflammatory cytokines, interleukin‐1beta (IL‐1beta) and interleukin‐6 (IL‐6), and other pro‐inflammatory mediators, such as matrix metalloprotease‐13 (MMP‐13), inducible nitric oxide synthase (iNOS), as well as HA levels and small HA fragment production. Treatment of RASF with antioxidants and specific HYAL1, HYAL2, and HYAL3 small interference RNA (siRNAs) significantly reduced TLR‐4 and CD44 increase in the mRNA expression and the related protein synthesis, as well as the release of inflammatory mediators up‐regulated by TNF‐α. These data suggest that the inhibition of HA degradation during arthritis may contribute to reducing TLR‐4 and CD44 activation and the inflammatory mediators response. J. Cell. Biochem. 113: 1852–1867, 2012. © 2012 Wiley Periodicals, Inc.
TGFβ‐inducible early gene‐1 (TIEG1) mutations in hypertrophic cardiomyopathy
Authors: Bos J. Martijn , Subramaniam Malayannan , Hawse John R. , Christiaans Imke , Rajamannan Nalini M. , Maleszewski Joseph J. , Edwards William D. , Wilde Arthur A.M. , Spelsberg Thomas C. , Ackerman Michael J.
Published: January 2012

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disease. A recent study showed that male KLF10‐encoded TGFβ Inducible Early Gene‐1 knock‐out mice (TIEG−/−) develop HCM with 13‐fold up‐regulation of PTTG1‐encoded pituitary tumor‐transforming gene 1. We hypothesized TIEG1 could be a novel candidate gene in the pathogenesis of genotype negative HCM in humans, possibly through a loss of its repression on PTTG1 expression. A cohort of 923 unrelated patients from two independent HCM centers was analyzed for mutations in TIEG's four translated exons using DHPLC and direct DNA‐sequencing. Site directed mutagenesis was performed to clone novel variants. The effect of TIEG1 mutations on SMAD7 and PTTG1 promoters was studied using transient transfection and luciferase‐assays. Altered expression of PTTG1 in cardiac tissue was studied by immunohistochemistry (IHC) to determine levels of PTTG1 protein in hypertrophic diseases. Six novel TIEG1 missense mutations were discovered in six patients (two males/four females, mean age at diagnosis 56.2 ± 23 years, MLVWT 20.8 ± 4 mm). Compared to WT TIEG1, five TIEG1 mutants significantly increased PTTG1 promoter function similar to TIEG1−/−‐mice. By IHC, PTTG1‐protein expression was significantly increased in multiple models of hypertrophic cardiac disease, including TIEG1‐mutation positive HCM compared to normal hearts. This is the first article to associate mutations in TIEG1 to human disease with the discovery of six novel, HCM‐associated variants. Functional assays suggest a role for PTTG1 in the pathogenesis of TIEG1‐mediated HCM. Up‐regulation of PTTG1 seems to be a common pathway in hypertrophic heart disease, including TIEG1‐mediated HCM. J. Cell. Biochem. 113: 1896–1903, 2012. © 2012 Wiley Periodicals, Inc.
Heme induced oxidative stress attenuates sirtuin1 and enhances adipogenesis in mesenchymal stem cells and mouse pre‐adipocytes
Authors: Puri Nitin , Sodhi Komal , Haarstad Michael , Kim Dong Hyun , Bohinc Steven , Foglio Eleonora , Favero Gaia , Abraham Nader G.
Published: January 2012

Patho‐physiological conditions with high oxidative stress, such as conditions associated with increased denatured heme‐proteins, are associated with enhanced adipogenic response. This effect predominantly manifests as adipocyte hypertrophy characterized by dysfunctional, pro‐inflammatory adipocytes exhibiting reduced expression of anti‐inflammatory hormone, adiponectin. To understand how increased levels of cellular heme, a pro‐oxidant molecule, modulates adipogenesis; the following study was designed to evaluate effects of heme on adipogenesis in human mesenchymal stem cells (hMSCs) and mouse pre‐adipocytes (3T3L1). Experiments were conducted in the absence and in the presence of a superoxide dismutase (SOD) mimetic (tempol, 100 µM). Heme (10 µM) increased (P < 0.05) adipogenesis in hMSCs and mouse pre‐adipocytes, where tempol alone (100 µmol/L) attenuated adipogenesis in these cells (P < 0.05). Tempol also reversed heme‐induced increase in adipogenesis in both hMSCs and mouse pre‐adipocytes (P < 0.05). In addition, heme exposed 3T3L1 exhibited reduced (P < 0.05) expression of transcriptional regulator—sirtuin 1 (Sirt1), along with, increased (P < 0.05) expression of adipogenic markers peroxisome proliferators‐activated receptor‐gamma (PPARγ), C/EBPα, and aP2. These effects of heme were rescued (P < 0.05) in cells concurrently treated with heme and tempol (P < 0.05) and prevented in cells over‐expressing Sirt1. Taken together, our results indicate that heme‐induced oxidative stress inhibits Sirt1, thus un‐inhibiting adipogenic regulators such as PPARγ and C/EBPα; which in turn induce increased adipogenesis along with adipocyte hypertrophy in pre‐adipocytes. Anti‐oxidant induced offsetting of these effects of heme supports the role of heme‐dependent oxidative stress in mediating such events. J. Cell. Biochem. 113: 1926–1935, 2012. © 2012 Wiley Periodicals, Inc.