bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Cardiac Resynchronization Therapy on Thyroid Function
Authors: Celikyurt Umut , Agacdiken Aysen , Geyik Bilal , Kozdag Guliz , Vural Ahmet , Ural Dilek
Published: September 2011

Background:

Heart failure patients frequently have thyroid function abnormalities. Cardiac resynchronization therapy (CRT) is a major treatment for patients with advanced chronic heart failure. We aimed to investigate the effects of CRT on thyroid functions.

Hypothesis:

CRT improves thyroid functions.

Methods:

Fifty‐seven patients (42 male, 15 female; mean age 58 ± 13 y) undergoing CRT were included in the study. Serum levels of thyroid hormones and echocardiographic parameters were measured before and 6 months after CRT. A response to CRT was defined as a reverse remodeling detected by a relative increase of ≥15% in left ventricular ejection fraction.

Results:

The clinical status and functional capacity of the patients in the remodeling group were improved significantly. The mean New York Heart Association class was reduced from 3.2 ± 0.4 to 2.2 ± 0.4 (P<0.001). The free triiodothyronine (fT3) level increased from 2.67 pg/mL to 2.97 pg/mL in the reverse remodeling group (P = 0.005). The fT3/fT4 ratio increased from 1.81 to 2.34 (P = 0.006).

Conclusions:

CRT improves fT3 levels and fT3/fT4 ratio, which may play an important role in reverse remodeling. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
“Entering a clinical trial: Is it right for you?”
Authors: Hoffner Brianna , Bauer‐Wu Susan , Hitchcock‐Bryan Suzanne , Powell Mark , Wolanski Andrew , Joffe Steven
Published: September 2011

PURPOSE:

This randomized study was designed to assess the utility of an educational video in preparing cancer patients for decisions about clinical trial participation. The study assessed the effect of the video on patients' understanding and perceptions of clinical trials, its impact on decision making and patient‐provider communication, and patients' satisfaction with the video.

METHODS:

Ninety adults considering cancer clinical trials were randomized to receive (n = 45) or not receive (n = 45) the video. Using the validated Quality of Informed Consent (QuIC), respondents' knowledge about clinical trial participation was assessed. All subjects completed additional questions about satisfaction with the video, decision making, and patient‐provider communication. Data were analyzed using the Wilcoxon rank‐sum test, regression model, and descriptive statistics.

RESULTS:

Although intent‐to‐treat analysis found no significant group differences in objective understanding between those randomized to view or not view the video, the majority of participants reported favorable experiences with regard to watching the video: 85% found the video was an important source of information about clinical trials; 81% felt better prepared to discuss the trial with their physician; 89% of those who watched the video with family indicated that it helped family better understand clinical trials; and 73% indicated it helped family accept their decision about participation.

CONCLUSIONS:

Although the video did not measurably improve patients' knowledge about clinical trials, it was an important source of information, helped educate families, and enhanced patient communication with their oncology providers. Cancer 2012;. © 2011 American Cancer Society.
Radiation field design and regional control in sentinel lymph node‐positive breast cancer patients with omission of axillary dissection
Authors: Setton Jeremy , Cody Hiram , Tan Lee , Morrow Monica , Hudis Clifford , Catalano Jeffrey , McCormick Beryl , Powell Simon , Ho Alice
Published: September 2011

BACKGROUND:

Randomized data suggest that axillary clearance is not necessary in select, clinically lymph node‐negative women with positive sentinel lymph node (SLN) biopsies (SLNBs) who undergo breast‐conserving surgery or receive whole‐breast radiotherapy and systemic therapy. The additional value of axillary radiotherapy in these patients is unknown.

METHODS:

The authors identified 326 patients with positive SLNBs who underwent breast‐conserving surgery without axillary lymph node dissection from 1997 to 2009. SLN tumor deposits measured ≤0.2 mm in 58% of patients, 0.3 to 2.0 mm in 35% of patients, and >2 mm in 7% Patients. Ninety‐three percent of patients received adjuvant radiotherapy. Radiation fields were categorized as standard tangents, high tangents, comprehensive (tangents plus supraclavicular), or partial breast to reflect coverage of the axilla. Standard tangents included both prone and supine positions. Regional failure was defined as recurrence in the ipsilateral supraclavicular, axillary, or internal mammary lymph nodes.

RESULTS:

The median follow‐up was 55 months (range, 1‐158 months). The 4‐year rates of regional control, local control, disease‐free survival, and overall survival were 99%, 98%, 95%, and 91%, respectively. Three patients had regional recurrences. Two of those patients received adjuvant radiotherapy with standard supine tangents, and 1 patient did not receive radiotherapy. No regional recurrences occurred among 66 patients who received radiotherapy in the prone position.

CONCLUSIONS:

Regional control was high (99% at 4 years) in patients who had low‐volume SLN disease who did not undergo axillary dissection, regardless of whether the axilla was irradiated. Whole‐breast radiation alone, including in the prone position, is sufficient treatment after breast‐conserving surgery for select patients with tumor‐containing SLNs who omit axillary dissection. Cancer 2012;. © 2011 American Cancer Society.
What Basic Emotions Are Experienced in Bipolar Disorder?
Authors: Carolan Louise A. , Power Mick J.
Published: September 2011

Aims

The aims of this study were to investigate the basic emotions experienced within and between episodes of bipolar disorder and, more specifically, to test the predictions made by the Schematic, Propositional, Analogical and Associative Representation Systems (SPAARS) model that mania is predominantly characterized by the coupling of happiness with anger whereas depression (unipolar and bipolar) primarily comprises a coupling between sadness and disgust.

Design

A cross‐sectional design was employed to examine the differences within and between the bipolar, unipolar and control groups in the emotional profiles. Data were analysed using one‐way ANOVAs.

Method

Psychiatric diagnoses in the clinical groups were confirmed using the Structured Clinical Interview for DSM‐IV (SCID). It was not administered in the control group. Current mood state was measured using the Beck Depression Inventory‐II, the State–Trait Anxiety Inventory and the Bech–Rafaelsen Mania Scale. The Basic Emotions Scale was used to explore the emotional profiles.

Results

The results confirmed the predictions made by the SPAARS model about emotions in mania and depression. Outwith these episodes, individuals with bipolar disorder experienced elevated levels of disgust.

Discussion

Evidence was found in support of the proposal of SPAARS that there are five basic emotions, which form the basis for both normal emotional experience and emotional disorders. Disgust is an important feature of bipolar disorder. Strengths and limitations are discussed, and suggestions for future research are explored. Copyright © 2011 John Wiley & Sons, Ltd.

Key Practitioner Message

There are five basic emotions which form the basis for emotional experience.

Disgust is an important feature of bipolar disorder.

These findings should be considered within clinical practice.
Influence of reduced working frequencies on the floating‐zone growth of silicon single crystals
Authors: Menzel R. , Rost A. , Luedge A. , Riemann H.
Published: September 2011

Lowering the working frequency in the inductively heated floating zone growth of Si Single crystals will reduce the risk of arcing at the induction coil. This is of particular interest in the growth of large diameter crystals. In the current paper we present results from growth experiments at lower frequencies, 2 MHz and 1.7 MHz. It is found that the growth of dislocation‐free crystals is possible at these frequencies and cause distinct changes in the interface deflection and radial resistivity profiles. Results from numerical simulation of the melt flow at different frequencies are presented. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
CVD of Poly(α,α′‐dimethyl‐p‐xylylene) and Poly(α,α,α′, α′‐tetramethyl‐p‐xylylene)‐co‐poly(p‐xylylene) from Alkoxide Precursors I: Optical Properties and Thermal Stability
Authors: Senkevich Jay J.
Published: September 2011

The parylene CVD platform is a unique one since it enables the room temperature deposition of high‐performance polymers from the resonance‐stabilization of the p‐xylylene intermediate. This intermediate, or the derivatives of it, have the same stabilization. Regardless of the precursor, albeit the more common [2.2] paracyclophane or monomer routes, there are two sites to derivatize the parylene precursor, the alpha or benzylic position or the phenyl ring. The work here explores the addition of methyl groups to the alpha position of p‐xylylene or parylene. The results show that the resulting polymer, poly(α,α′‐dimethyl‐p‐xylylene) shares many of the properties of parylene E (phenyl‐modified ethylated parylene); however, with a higher thermal stability, 400 °C. A homopolymer of poly(α,α,α′,α′‐tetramethyl‐p‐xylylene) is not possible due to steric hinderance of the methyl groups, but an alternating copolymer, poly(α,α,α′,α′‐tetramethyl‐p‐xylylene)‐co‐poly(p‐xylylene), is deposited.
Heterogeneous wireless access technology and its impact on forming and maintaining friendship through mobile social networks
Authors: Ou Shumao , Pan Hui , Li Feng
Published: September 2011

Advances in wireless access technology have enabled mobile users to gain access to online social networks anywhere and any time. This paper investigates friendship formation in online social networks with the support of heterogeneous wireless access. A network‐aware friendship formation model is proposed that takes the network communication cost into account. A social network‐aware scheduling scheme is also proposed that schedules user data into a wireless access subsystem satisfying the minimum QoS requirements and with the lowest delivery cost. Simulation results have verified the proposed model and showed the effectiveness of the proposed scheduling mechanism. Copyright © 2011 John Wiley & Sons, Ltd.
Squamous cell carcinoma with rhabdoid phenotype of skin/soft tissue in a transplant patient: An exceptional case and review of the literature
Authors: Allam‐Nandyala Pushpa , Bui Marilyn M. , DeConti Ronald , Purohit Chetna , Altiok Soner
Published: September 2011

Squamous cell carcinoma with rhabdoid features (SCCRF) is a very rare and unusual cutaneous tumor. Here, we report an extraordinary case diagnosed by fine needle aspiration biopsy, in a 66‐year‐old man, status post multiple organ transplantation. The patient presented with a large ulcerating fungating mass in his forearm that had all the light microscopic and immunohistochemical features of a SCCRF. Previously six cases of SCCRF phenotype diagnosed by surgical pathology have been reported. This is the first case diagnosed cytologically. A review of the literature with emphasis on the differential diagnoses of such unusual rhabdoid‐like tumors in fine‐needle aspiration biopsy and the potential molecular mechanism for rhabdoid phenotype in transplant patients are discussed. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc
Mouse transgenic lines that selectively label type I, type IIa, and types IIX+B skeletal muscle fibers
Authors: Chakkalakal Joe V. , Kuang Shihuan , Buffelli Mario , Lichtman Jeff W. , Sanes Joshua R.
Published: September 2011

Skeletal muscle fibers vary in contractile and metabolic properties. Four main fiber types are present in mammalian trunk and limb muscles; they are called I, IIA, IIX, and IIB, ranging from slowest‐ to fastest‐contracting. Individual muscles contain stereotyped proportions of two or more fiber types. Fiber type is determined by a combination of nerve‐dependent and ‐independent influences, leading to formation of “homogeneous motor units” in which all branches of a single motor neuron form synapses on fibers of a single type. Fiber type composition of muscles can be altered in adulthood by multiple factors including exercise, denervation, hormones, and aging. To facilitate analysis of muscle development, plasticity, and innervation, we generated transgenic mouse lines in which Type I, Type IIA, and Type IIX+B fibers can be selectively labeled with distinguishable fluorophores. We demonstrate their use for motor unit reconstruction and live imaging of nerve‐dependent alterations in fiber type. genesis 50:50–58, 2012. © 2011 Wiley Periodicals, Inc.
Post‐Pleistocene range expansion of the recently imperiled eastern little brown bat (Myotis lucifugus lucifugus) from a single southern refugium
Authors: Dixon Michael D.
Published: September 2011

Myotis lucifugus, once among the most widespread and common bats in North America, has been forecast to be extirpated east of the Rockies in as few as 16 years by the spread of white‐nose syndrome. Recent genetic research has demonstrated that this species is paraphyletic and part of a broader species complex; however, only one lineage (Myotis lucifugus lucifugus [M. l. lucifugus]) is present in eastern North America. I used molecular tools and niche modeling to validate this and investigate the role that historical biogeography has played in the phylogenetic and population genetic structure of this species to determine if the eastern subspecies represents an evolutionarily distinct population.

To establish the genetic structure within M. l. lucifugus, I densely sampled maternity colonies in Minnesota and sequenced 182 individuals for a portion of cytochrome b. Phylogenetic reconstruction and a haplotype network were used to infer the relationships among mitochondrial haplotypes. Population growth statistics were calculated to determine if there was evidence of significant expansion, and an environmental niche model (ENM) was constructed based on conditions during the last glacial maximum (LGM) to illustrate potential glacial refugia. All individuals derived from a single mitochondrial lineage. Genetic evidence points to population growth starting approximately 18 kya. ENM results show that there was likely a single large southern refugium extending across the southeastern United States and possibly several isolated refugia in western North America. Myotis lucifugus lucifugus likely maintained both a large range and a large population during the peaks of the glacial cycles, and its population appears to have expanded following the retreat of the Laurentide ice sheet. This imperiled lineage likely diverged in isolation from other members of the M. lucifugus/western long‐eared Myotis during the Pleistocene.
Using Metal Carbonyl Clusters To Develop a Molecular Approach towards Metal Nanoparticles
Authors: Zacchini Stefano
Published: September 2011

This microreview aims at presenting a personal perspective on the possible contributions of molecular metal carbonyl clusters (MCCs) to a better understanding and development of metal nanoparticles. High‐nuclearity molecular MCCs are perfectly (atomically) monodisperse, ligand‐stabilised metal nanoparticles with nanometric dimensions. Thus, when the nuclearity of molecular clusters is increased and the dimensions of metal nanoparticles are reduced, these two worlds begin to overlap. Herein, the synthesis of larger MCCs is briefly outlined, together with the description of their structural features and physical properties. The use of molecular MCCs as nanometric or subnanometric building blocks for self‐assembly of functional nanomaterials is also reported. Finally, the employment of MCCs as precursors for metal nanoparticles after decomposition of the molecular precursor is described. The purpose of this microreview is to discuss some representative examples of all these topics, showing that one of the most promising and fascinating aspects of molecular MCCs is their borderline nature between molecular chemistry and nanochemistry.
Hierarchical Durian‐Shaped Dodecahedral Rutile Microparticles
Authors: Liu Jia , Yang Xianfeng , Wen Yuping , Gao Qiong , Zhou Qiang , Liang Chaolun , Wu Mingmei
Published: September 2011

Hierarchical durian‐shaped dodecahedrons of rutile have been synthesized hydrothermally from titanium n‐butoxide (TNB) in oxalic acid. The products are characterized by powder X‐ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and selected‐area electron diffraction (SAED) and the hierarchical architectures of these dodecahedrons have been addressed. It is suggested that the growth of the hierarchical rutile architectures is directly from a precursor, titanium oxide oxalate hydroxide hydrate [Ti2O2(C2O4)(OH)2·H2O, briefly denoted as TOOHH], which can be formed at an earlier stage during hydrothermal synthesis, typically at lower reaction temperature. The production of the novel hierarchical nanostructure is attributed to epitaxial growth along some specific directions and the chemical etching and growth is due to similarities of corner‐sharing TiO2 octahedrons between rutile and TOOHH.
Enantioselectivity of monolithic silica stationary phases immobilized with different concentrations cellulose tris (3,5‐dimethylphenylcarbamate), analyzed with different mobile phases in capillary electrochromatography
Authors: Lv Chunguang , Liu Yueqi , Mangelings Debby , Vander Heyden Yvan
Published: September 2011

The 3,5‐dimethylphenylcarbamate derivatives of cellulose bearing 3‐(triethoxysilyl)propyl residues were immobilized in a capillary format onto a monolithic silica support by intermolecular polycondensation of the triethoxysilyl groups. The resulting columns were used for chiral separations using capillary electrochromatography. The effects of the synthesizing solvent, the selector coating procedure, the chiral selector concentration onto the silica monolith and the mobile phase pH value, on the separation of enantiomers were studied. The column‐to‐column reproducibility and stability also were evaluated. A test set of 14 chiral substances, including acidic, neutral, bifunctional and basic compounds, was used to investigate the effects of the factors mentioned above. Twelve pairs of enantiomers showed enantioselectivity at some of the different conditions tested. The column‐to‐column repeatability was satisfactory, and the prepared columns were stable under the adopted analysis conditions.
Report on stage III Pig‐a mutation assays using benzo[a]pyrene
Authors: Bhalli Javed A. , Shaddock Joseph G. , Pearce Mason G. , Dobrovolsky Vasily N. , Cao Xuefei , Heflich Robert H. , Vohr Hans‐Werner
Published: September 2011

Genotoxicity assays were conducted on rats treated with benzo[a]pyrene (BaP) as part of Stage III of a validation study on the Pig‐a gene mutation assay. Assays were performed at the U.S. FDA‐NCTR and Bayer‐Germany. Starting on Day 1, groups of five 6‐ to 7‐week‐old male Fischer 344 (F344, used at FDA‐NCTR) and Han Wistar rats (Bayer) were given 28 daily doses of 0, 37.5, 75, or 150 mg/kg BaP; blood was sampled on Days −1, 4, 15, 29, and 56. Pig‐a mutant frequencies were determined on Days −1, 15, 29, and 56 in total red blood cells (RBCs) and reticulocytes (RETs) as RBCCD59− and RETCD59− frequencies; percent micronucleated‐RETs (%MN‐RET) were measured on Days 4 and 29. RBCCD59− and RETCD59− frequencies increased in a dose‐ and time‐dependent manner, producing significant increases by Day 29 in both rat models. The responses for RETs were stronger than those for RBCs, and the responses in F344 rats were stronger than in Han Wistar rats. BaP also produced significant increases in %MN‐RET frequency at Days 4 and 29, with the responses being greater in F344 than Han Wistar rats. The overall findings were consistent with those of the reference laboratory using Han Wistar rats. Finally, mutation assays performed on splenocytes from Day 56 F344 rats indicated that BaP mutant frequencies were three to fivefold higher for the Hprt gene than the Pig‐a gene. The results indicate that the Pig‐a RET and RBC assays are reproducible, transferable, and show promise for integrating gene mutation into 28‐day repeat‐dose studies. Environ. Mol. Mutagen. 2011. © 2011 Wiley‐Liss, Inc.
Cross‐layer design for double‐string cooperative communications in wireless ad‐hoc networks
Authors: Sergi S. , Pancaldi F. , Vitetta G.M.
Published: September 2011

This paper proposes a novel architecture for cooperative communication in wireless ad‐hoc networks capable of offering reliable and low‐latency services efficiently. The proposed solution is characterised by the following relevant features: (i) a wireless connection between each couple of network nodes is established via multiple relays; (ii) each source‐to‐destination link is characterised by a double‐string topology, allowing the use of specific transmit diversity techniques for reliable communications; and (iii) a novel utility‐based routing metric providing a fair exploitation of the available energy/bandwidth resources is employed. Simulation results evidence that our solution offers substantial energy savings with respect to traditional ad‐hoc architectures employing multihop routing and operating in the absence of cooperative strategies. Copyright © 2011 John Wiley & Sons, Ltd.
Steady flow and heat transfer of a magnetohydrodynamic Sisko fluid through porous medium in annular pipe
Authors: Khan M. , Shaheen N. , Shahzad A.
Published: September 2011

In this paper, the steady flow and heat transfer of a magnetohydrodynamic fluid is studied. The fluid is assumed to be electrically conducting in the presence of a uniform magnetic field and occupies the porous space in annular pipe. The governing nonlinear equations are modeled by introducing the modified Darcy's law obeying the Sisko model. The system is solved using the homotopy analysis method (HAM), which yields analytical solutions in the form of a rapidly convergent infinite series. Also, HAM is used to obtain analytical solutions of the problem for noninteger values of the power index. The resulting problem for velocity field is then numerically solved using an iterative method to show the accuracy of the analytic solutions. The obtained solutions for the velocity and temperature fields are graphically sketched and the salient features of these solutions are discussed for various values of the power index parameter. We also present a comparison between Sisko and Newtonian fluids. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular profiling reveals frequent gain of MYCN and anaplasia‐specific loss of 4q and 14q in wilms tumor
Authors: Williams Richard D. , Al‐Saadi Reem , Natrajan Rachael , Mackay Alan , Chagtai Tasnim , Little Suzanne , Hing Sandra N. , Fenwick Kerry , Ashworth Alan , Grundy Paul , Anderson James R. , Dome Jeffrey S. , Perlman Elizabeth J. , Jones Chris , Pritchard‐Jones Kathy
Published: September 2011

Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia‐specific genomic loss and under‐expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. © 2011 Wiley Periodicals, Inc.
A putative “hepitype” in the ATM gene associated with chronic lymphocytic leukemia risk
Authors: Martín‐Guerrero Idoia , Enjuanes Anna , Richter Julia , Ammerpohl Ole , Colomer Dolors , Ardanaz Maite , Marco Fernando , Salas Antonio , Campo Elias , Siebert Reiner , García‐Orad Africa
Published: September 2011

Chronic lymphocytic leukemia (CLL) cells are characterized by several chromosomal lesions. Some of these aberrations imply chromosome breaks as a result of unrepaired double strand breaks (DSBs) in the DNA. The ATM (ataxia telangiectasia‐mutated) protein is the principal integrator of cellular responses to DSBs. ATM deletion is also an adverse prognostic factor in CLL. Taking this into account, we evaluated if genetic and/or epigenetic variation in the ATM gene may modulate the individual susceptibility to develop CLL. Our case‐control association study was performed in a large Spanish population of 1,503 individuals, including 742 patients with CLL and 761 controls. We identified one haplotype within the ATM gene that confers an increased risk of CLL development (OR = 1.33; 95% CI: 1.10–1.60). Two polymorphisms of this ATM haplotype eliminated one CpG site each in Introns 15 and 61, causing changes in DNA methylation pattern. These data provide the first evidence for the existence of a putative “hepitype” in the ATM gene associated with CLL risk.© 2011 Wiley‐Liss, Inc.
Identification of altered MicroRNA expression in canine lymphoid cell lines and cases of B‐ and T‐Cell lymphomas
Authors: Uhl Elizabeth , Krimer Paula , Schliekelman Paul , Tompkins S. Mark , Suter Steven
Published: September 2011

Canine lymphoma is a common spontaneous tumor with many similarities to human lymphoma, and thus has potential to be an important animal model of lymphomagenesis. This study determined that microRNA (miRNA) expression in canine tumors can be assessed using a commercially available human cancer miRNA qPCR array. miRNA expression in six different canine lymphoid cell lines and in naturally occurring canine B‐ and T‐cell lymphomas was compared using RNA harvested from normal canine peripheral blood mononuclear cells (PBMC) and normal lymph nodes (LN) as controls. We found that false discovery rate (FDR) correction for multiple testing after quantile normalization controlled for variation across arrays and that they were the best methods for normalization and statistical analysis. Increases in miRNAs known to upregulate oncogenes (miR19a+b, miR17‐5p) and decreased expression of miRNAs with tumor suppressor functions (miR‐203, miR‐218, and miR‐181a) also seen in human lymphoid malignancies were observed. However, there were few similarities between canine groups. The results of this study indicate that the use of both PBMC and LN cells as controls provides different, but potentially equally important targets for further analysis. Our findings of miRNA dysregulation in canine lymphoid cell lines and clinical cases of lymphoma emphasize the potential of canine lymphoma as an important spontaneous, large animal model of human B‐ and T‐cell lymphomas. © 2011 Wiley‐Liss, Inc.
Microglial zinc uptake via zinc transporters induces ATP release and the activation of microglia
Authors: Higashi Youichirou , Segawa Shohei , Matsuo Takaaki , Nakamura Shogo , Kikkawa Yukiko , Nishida Kentaro , Nagasawa Kazuki
Published: September 2011

Previously, we demonstrated that extracellular zinc plays a key role in transient global ischemia‐induced microglial activation through sequential activation of NADPH oxidase and poly(ADP‐ribose) polymerase (PARP)‐1. However, it remains unclear how zinc causes the sequential activation of microglia. Here, we examined whether transporter‐mediated zinc uptake is necessary for microglial activation. Administration of zinc to microglia activated them through reactive oxygen species (ROS) generation and poly(ADP‐ribose) (PAR) formation, which were suppressed by intracellular zinc chelation with 25 μM TPEN (N,N,N′,N′‐tetrakis(2‐pyridylmethyl)ethylenediamine) or 2 μM BAPTA‐AM (1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester). The 65Zn uptake by microglia was temperature‐ and dose‐dependent, and it was blocked by metal cations, but not by L‐type calcium channel blockers nifedipine and nimodipine. Expression of Zrt‐Irt‐like protein (ZIP)1, a plasma membrane‐type zinc transporter, was detected in microglia, and nickel, a relatively sensitive substrate/inhibitor of ZIP1, showed cis‐ and trans‐inhibitory effects on the 65Zn uptake. Exposure of microglia to zinc increased the extracellular ATP concentration, which was suppressed by intracellular zinc chelation and inhibition of hemichannels. mRNA expression of several types of P2 receptors was detected in microglia, and periodate‐oxidized ATP, a selective P2×7 receptor antagonist, attenuated the zinc‐induced microglial activation via NADPH oxidase and PARP‐1. Exogenous ATP and 2′(3′)‐O‐(4‐benzoyl‐benzoyl) ATP also caused microglial activation through ROS generation and PAR formation. These findings demonstrate that ZIP1‐mediated uptake of zinc induces ATP release and autocrine/paracrine activation of P2X(7) receptors, and then activates microglia, suggesting that zinc transporter‐mediated uptake of zinc is a trigger for microglial activation via the NADPH oxidase and PARP‐1 pathway. © 2011 Wiley‐Liss, Inc.
Multivariate patterns of brain–cognition associations relating to vulnerability and clinical outcome in the at‐risk mental states for psychosis
Authors: Koutsouleris Nikolaos , Gaser Christian , Patschurek‐Kliche Katja , Scheuerecker Johanna , Bottlender Ronald , Decker Petra , Schmitt Gisela , Reiser Maximilian , Möller Hans‐Jürgen , Meisenzahl Eva M.
Published: September 2011

Background: Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto‐temporo‐limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at‐risk mental states (ARMS) for psychosis. However, structure–cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques. Methods: Voxel‐based morphometry and partial least squares were employed to study system‐level covariance patterns between whole‐brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure–cognition covariance patterns were tested for significance and reliability using non‐parametric permutation and bootstrap resampling. Results: We identified ARMS‐specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto‐temporo‐limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions. Conclusions: These findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi‐domain neurocognitive measures to a set of prefronto‐temporo‐limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain–cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes. Hum Brain Mapp 33:2104–2124, 2012. © 2011 Wiley Periodicals, Inc.
Optimizing the performance of local canonical correlation analysis in fMRI using spatial constraints
Authors: Cordes Dietmar , Jin Mingwu , Curran Tim , Nandy Rajesh
Published: September 2011

The benefits of locally adaptive statistical methods for fMRI research have been shown in recent years, as these methods are more proficient in detecting brain activations in a noisy environment. One such method is local canonical correlation analysis (CCA), which investigates a group of neighboring voxels instead of looking at the single voxel time course. The value of a suitable test statistic is used as a measure of activation. It is customary to assign the value to the center voxel for convenience. The method without constraints is prone to artifacts, especially in a region of localized strong activation. To compensate for these deficiencies, the impact of different spatial constraints in CCA on sensitivity and specificity are investigated. The ability of constrained CCA (cCCA) to detect activation patterns in an episodic memory task has been studied. This research shows how any arbitrary contrast of interest can be analyzed by cCCA and how accurate P‐values optimized for the contrast of interest can be computed using nonparametric methods. Results indicate an increase of up to 20% in detecting activation patterns for some of the advanced cCCA methods, as measured by ROC curves derived from simulated and real fMRI data. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Concurrent chemoradiotherapy for locoregionally advanced salivary gland malignancies
Authors: Rosenberg Lewis , Weissler Mark , Hayes D. Neil , Shockley William , Zanation Adam , Rosenman Julian , Chera Bhishamjit
Published: September 2011

Background

Locoregionally advanced salivary gland malignancies have a poor prognosis despite aggressive therapy. Herein we report our experience in treating high‐risk salivary gland malignancies with concurrent chemoradiotherapy (CRT).

Methods

Medical records of 15 patients with salivary gland malignancies treated with CRT at our institution between 1997 and 2010 were analyzed.

Results

All patients had high‐risk characteristics: 80% were stage IV, 54% were ≥N2, and 47% were unresectable and were treated with definitive CRT. At 2 years, overall survival (OS) was 67%, disease‐free survival (DFS) was 44%, and local control was 76%. There were no treatment‐related deaths, and patients experienced expected acute side effects.

Conclusion

CRT for salivary gland malignancies has acceptable toxicity, CRT is proven beneficial for many other cancers, and some salivary gland malignancies are clinically responsive to chemotherapy. CRT, therefore, should be considered for treatment of high‐risk salivary gland malignancies. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Dendritic Cell Regulation of Carbon Tetrachloride–Induced Murine Liver Fibrosis Regression
Authors: Jiao Jingjing , Sastre David , Fiel Maria Isabel , Lee Ursula E. , Ghiassi–Nejad Zahra , Ginhoux Florent , Vivier Eric , Friedman Scott L. , Merad Miriam , Aloman Costica
Published: September 2011

Although hepatic fibrosis typically follows chronic inflammation, fibrosis will often regress after cessation of liver injury. In this study, we examined whether liver dendritic cells (DCs) play a role in liver fibrosis regression using carbon tetrachloride to induce liver injury. We examined DC dynamics during fibrosis regression and their capacity to modulate liver fibrosis regression upon cessation of injury. We show that conditional DC depletion soon after discontinuation of the liver insult leads to delayed fibrosis regression and reduced clearance of activated hepatic stellate cells, the key fibrogenic cell in the liver. Conversely, DC expansion induced either by Flt3L (fms–like tyrosine kinase–3 ligand) or adoptive transfer of purified DCs accelerates liver fibrosis regression. DC modulation of fibrosis was partially dependent on matrix metalloproteinase (MMP)–9, because MMP–9 inhibition abolished the Flt3L–mediated effect and the ability of transferred DCs to accelerate fibrosis regression. In contrast, transfer of DCs from MMP–9–deficient mice failed to improve fibrosis regression.

Conclusion

: Taken together, these results suggest that DCs increase fibrosis regression and that the effect is correlated with their production of MMP–9. The results also suggest that Flt3L treatment during fibrosis resolution merits evaluation to accelerate regression of advanced liver fibrosis. (Hepatology 2012;55:243–255)
Precipitable water conversion rates over the Qinghai‐Xizang (Tibet) Plateau: changing characteristics with global warming
Authors: Wang Chenghai , Guo Yipeng
Published: September 2011

In this article, the trends and variability of precipitation and precipitable water (PW) over the Qinghai‐Xizang (Tibet) Plateau (QXP) (1970–2009) were analysed by using ERA‐40 (The European Center for Medium‐Range Weather Forecasts (ECMWF) 40 years Re‐analysis) and NCEP (The National Centers for Environmental Prediction)/NCAR reanalyses data and the ground observed precipitation data from 60 sites. The results showed that the precipitation over the QXP had an overall increasing trend; however, a slight decreasing trend was observed over the southeast. This decreasing precipitation trend might be related to the South Asia monsoon degradation. Since 1970, a decreasing PW trend has occurred over the QXP in which the southeast is the most significant region. Because of the rising temperatures in the QXP, a remarkable PW conversion rate (PWCR) increase of 0.87% per decade has occurred over the past 40 years. Because of its steep terrain, the PWCR in the middle eastern region of the QXP increased faster than that of the other regions. The mean PWCR in the wet southern region of the QXP was higher than that of the dry northern region, which was higher in the winter than that in the summer. Although much precipitation occurred in the summer, in the wet regions, the PWCR was higher in the winter than in the summer. The PWCR peak in the wet and dry regions occurred during the precipitation‐short and precipitation‐sufficient seasons, respectively. Copyright © 2011 John Wiley & Sons, Ltd.
Recharge estimation using remotely sensed evapotranspiration in an irrigated catchment in southeast Australia
Authors: Githui F. , Selle B. , Thayalakumaran T.
Published: September 2011

Reliable estimates of groundwater recharge are required for the sustainable management of surface and ground water resources in semi‐arid regions particularly in irrigated regions. In this study, groundwater recharge was estimated for an irrigated catchment in southeast Australia using a semi‐distributed hydrological model (SWAT). The model was calibrated under the dry climatic conditions for the period from August 2002 to July 2003 using flow and remotely sensed evapotranspiration (ET). The model was able to simulate observed monthly drain flow and spatially distributed remotely sensed ET. Recharge tended to be higher for irrigated land covers, such as perennial pasture, than for non‐irrigated land. On average, the estimated annual catchment recharge ranged between 147 and 289 mm which represented about 40% of the total rainfall and irrigation inputs. The optimized soil parameters indirectly reflected flow bypassing the soil matrix that could be responsible for this substantial amount of recharge. Overall, the estimated recharge was much more than that previously estimated for the wetter years. Copyright © 2011 John Wiley & Sons, Ltd.
Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: Reduction of Wnt‐associated proteins and reduced translocation of galectin‐3‐mediated β‐catenin to the nucleus
Authors: Dakeng Sumana , Duangmano Suwit , Jiratchariyakul Weena , U‐Pratya Yaowalak , Bögler Oliver , Patmasiriwat Pimpicha
Published: August 2011

The cucurbitacins are tetracyclic triterpenes found in plants of the family Cucurbitaceae. Cucurbitacins have been shown to have anti‐cancer and anti‐inflamatory activities. We investigated the anti‐cancer activity of cucurbitacin B extracted from Thai medicinal plant Trichosanthes cucumerina Linn. Cell viability was assessed by MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Results indicated that cucurbitacin B from T. cucumerina Linn. has a cytotoxic effect on breast cancer cell lines SKBR‐3 and MCF‐7 with an IC50 of 4.60 and 88.75 µg/ml, respectively. Growth inhibition was attributed to G2/M phase arrest and apoptosis. Cyclin D1, c‐Myc, and β‐catenin expression levels were reduced. Western blot analysis showed increased PARP cleavage and decreased Wnt‐associated signaling molecules β‐catenin, galectin‐3, cyclin D1 and c‐Myc, and corresponding changes in phosphorylated GSK‐3β levels. Cucurbitacin B treatment inhibited translocation to the nucleus of β‐catenin and galectin‐3. The depletion of β‐catenin and galectin‐3 in the nucleus was confirmed by cellular protein fractionation. T‐cell factor (TCF)/lymphoid enhancer factor (LEF)‐dependent transcriptional activity was disrupted in cucurbitacin B treated cells as tested by a TCF reporter assay. The relative luciferase activity was reduced when we treated cells with cucurbitacin B compound for 24 h. Our data suggest that cucurbitacin B may in part induce apoptosis and exert growth inhibitory effect via interruption the Wnt signaling. J. Cell. Biochem. 113: 49–60, 2012. © 2011 Wiley Periodicals, Inc.
The basic helix loop helix transcription factor twist1 is a novel regulator of ATF4 in osteoblasts
Authors: Danciu Theodora E. , Li Yan , Koh Amy , Xiao Guozhi , McCauley Laurie K. , Franceschi Renny T.
Published: August 2011

Parathyroid hormone (PTH) is an essential regulator of endochondral bone formation and an important anabolic agent for the reversal of bone loss. PTH mediates its functions in part by regulating binding of the bone‐related activating transcription factor 4 (ATF4) to the osteoblast‐specific gene, osteocalcin. The basic helix‐loop‐helix (bHLH) factors Twist1 and Twist2 also regulate osteocalcin transcription in part through the interaction of the C‐terminal “box” domain in these factors and Runx2. In this study, we discovered a novel function of PTH: its ability to dramatically decrease Twist1 transcription. Since ATF4 is a major regulator of the PTH response in osteoblasts, we assessed the mutual regulation between these factors and determined that Twist proteins and ATF4 physically interact in a manner that affects ATF4 DNA binding function. We mapped the interaction domain of Twist proteins to the C‐terminal “box” domain and of ATF4, to the N‐terminus. Furthermore, we demonstrate that Twist1 overexpression in osteoblasts attenuates ATF4 binding to the osteocalcin promoter in response to PTH. This study thus identifies Twist proteins as novel inhibitory binding partners of ATF4 and explores the functional significance of this interaction. J. Cell. Biochem. 113: 70–79, 2012. © 2011 Wiley Periodicals, Inc.
Decreased bone mineral density and reduced bone quality in H+/K+ATPase beta‐subunit deficient mice
Authors: Fossmark Reidar , Stunes Astrid K. , Petzold Christiane , Waldum Helge L. , Rubert Marina , Lian Aina‐Mari , Reseland Janne E. , Syversen Unni
Published: September 2011

Proton pump inhibitors (PPIs) are widely used against gastroesophageal reflux disease. Recent epidemiological studies suggest that PPI users have an increased risk of fractures, but a causal relationship has been questioned. We have therefore investigated the skeletal phenotype in H+/K+ATPase beta‐subunit knockout (KO) female mice. Skeletal parameters were determined in 6‐ and 20‐month‐old KO mice and in wild‐type controls (WT). Whole body bone mineral density (BMD) and bone mineral content (BMC) were measured by dual energy X‐ray absorptiometry (DXA). Femurs were examined with µCT analyses and break force were examined by a three‐point bending test. Plasma levels of gastrin, RANKL, OPG, osteocalcin, leptin, and PTH were analyzed. KO mice had lower whole body BMC at 6 months (0.53 vs. 0.59 g, P = 0.035) and at 20 months (0.49 vs. 0.74 g, P < 0.01) compared to WT as well as lower BMD at 6 months (0.068 vs. 0.072 g/cm2, P = 0.026) and 20 months (0.067 vs. 0.077 g/cm2, P < 0.01). Mechanical strength was lower in KO mice at the age of 20 months (6.7 vs. 17.9 N, P < 0.01). Cortical thickness at 20 months and trabecular bone volume% at 6 months were significantly reduced in KO mice. Plasma OPG/RANKL ratio and PTH was increased in KO mice compared to controls. H+/K+ATPase beta subunit KO mice had decreased BMC and BMD, reduced cortical thickness and inferior mechanical bone strength. Whereas the mechanism is uncertain, these findings suggest a causal relationship between long‐term PPI use and an increased risk of fractures. J. Cell. Biochem. 113: 141–147, 2012. © 2011 Wiley Periodicals, Inc.
Facilitation of human osteoblast apoptosis by sulindac and indomethacin under hypoxic injury
Authors: Liu Cheng , Tsai An‐Ly , Chen Yen‐Chu , Fan Shih‐Chen , Huang Chun‐Hsien , Wu Chia‐Ching , Chang Chih‐Han
Published: September 2011

Hypoxic–ischemia injury occurs after trauma causes consequential bone necrosis. Non‐steroid anti‐inflammatory drugs (NSAIDs) are frequently used in orthopedic clinics for pain relief. However, the underlying mechanism and outcome for usage of NSAIDs is poorly understood. To investigate the damage and loss of osteoblast function in hypoxia, two hypoxia mimetics, cobalt chloride (CoCl2) and desferrioxamine (DFO), were used to create an in vitro hypoxic microenvironment. The cell damage was observed by decreases of cell viability and increases in cyclooxygenase‐2 and cleaved poly(ADP‐ribose) polymerase (PARP). Cell apoptosis was confirmed by WST‐1 cytotoxic assays and flow cytometry. The functional expression of osteoblast in alkaline phosphatase (ALP) activity was significantly decreased by CoCl2 and inhibited when treated with DFO. To simulate the use of NSAID after hypoxic injury, four types of anti‐inflammatory drugs, sulindac sulfide (SUL), indomethacin (IND), aspirin (Asp), and sodium salicylate (NaS), were applied to osteoblasts after 1 h of hypoxia mimetic treatment. SUL and IND further enhanced cell death after hypoxia. ALP activity was totally abolished in hypoxic osteoblasts under IND treatment. Facilitation of osteoblast apoptosis occurred regardless of IND dosage under hypoxic conditions. To investigate osteoblast in vivo, local hypoxia was created by fracture of tibia and then treated the injured mice with IND by oral feeding. IND‐induced osteoblast apoptosis was confirmed by positive staining of TUNEL assay in fractured mice. Significant delay of fracture healing in bone tissue was also observed with the treatment of IND. These results provide information pertaining to choosing appropriate anti‐inflammatory drugs for orthopedic patients. J. Cell. Biochem. 113: 148–155, 2012. © 2011 Wiley Periodicals, Inc.