bluuebunny/crossref_metadata_2025 huggingface dataset:
A Psychoneuroimmunologic Examination of Cumulative Perinatal Steroid Exposures and Preterm Infant Behavioral Follow-Up
Authors: Purdy Isabell B. , Smith Lynne , Wiley Dorothy , Badr Lina
Published: September 2011

Purpose:

This study’s aim was to explore relationships between preterm infant behavioral outcomes and maternal/infant glucocorticoid (dexamethasone [DEX]) treatments using a psychoneuroimmunologic approach. Research questions were (a) do relationships exist between infant cumulative perinatal steroid (PNS) exposure and child behavioral problems? and (b) do maternal/infant characteristics (e.g., immune markers and biophysiologic stressors) influence these relationships?

Methods:

The convenience sample comprised 45 mother–child dyads in which the children (mean age 8 years ± 2.3) had been born at a mean postconceptional age of 28 weeks (± 4.2). We used the Child Behavior Checklist (CBCL) to assess behavior, the Clinical Risk Index for Babies (CRIB) to score stress at birth, and retrospective record review to identify additional perinatal factors (PNS dosage, sepsis, and maternal and infant complete blood counts near delivery).

Results:

Children were dichotomized into high (> 0.2mg/kg; n = 20) versus low–no (≤0.2 mg/kg; n = 25) PNS exposure groups. Significant relationships existed between CBCL Total Problems score and sepsis, PNS exposure, timing of initial PNS, and infant length percentile at discharge. Competence problems were significantly associated with PNS, neonatal intensive care unit (NICU) infant length percentile, CRIB score, sepsis, retinopathy of prematurity, hearing deficit, and immunity markers (i.e., maternal lymphocyte percentage and infant band/seg ratio). Children in the higher PNS group exhibited more behavioral problems (e.g., withdrawn, attention, conduct, social, and rule breaking problems), but there were no significant differences. The findings are reassuring regarding long-term effects of this PNS dose on preterm infant behavioral outcomes.
Dire forecast: A theoretical model of the impact of climate change on crime
Authors: Agnew Robert
Published: September 2011

After providing an overview of climate change and its effects, this article draws on the leading crime theories to discuss the potential impact of climate change on crime. It is argued that climate change will increase strain, reduce social control, weaken social support, foster beliefs favorable to crime, contribute to traits conducive to crime, increase certain opportunities for crime, and create social conflict. An overall model of climate change and crime is then presented, along with suggestions for research. Even though neglected by criminologists, there is good reason to believe that climate change will become one of the major forces driving crime as the century progresses.
Evaluation of Daylighting Effectiveness and Energy Saving Potentials of Light-Pipe Systems in Buildings
Authors: Shin Ju Young , Yun Geun Young , Kim Jeong Tai
Published: September 2011

A light pipe system is a simple daylighting device that allows the natural daylight to enter into interior spaces or underground spaces where access to windows or skylights is restricted. The use of a light pipe system can enhance illuminance without the use of artificial lighting and thus would reduce energy consumption significantly. This paper presents a performance prediction method of a light pipe system based on the amount of daylight admitted and energy saved by not needing electric lighting. The newly developed model was compared with the existing prediction model under the Korean climate conditions, to illustrate the reliability and robustness of the method. Energy saving potential due to the use of a light pipe system was determined with a due consideration of the different artificial lighting control methods (on and off control, two-step control, dimming control), demonstrating a possible saving in lighting energy usage of up to 30% in average. This study should encourage a wider application of light-pipe system in Korea especially in high rise buildings where day-lighting could be limiting; thus increasing the options for architectural design for building application.
‘You’ve got to keep account of heads all the time’: staff perceptions of caring for people with dementia
Authors: Stockwell-Smith Gillian , Jones Cindy , Moyle Wendy
Published: September 2011

Research aim: Little is known regarding the pressures of working within dementia care units, as the majority of literature has focused broadly on long-term care rather than the provision of specialised dementia care. This study aimed to explore the perceptions of staff in relation to their capacity to manage behaviour and care needs of people with dementia living within the dementia-specific environment. Individual interviews were conducted with 35 care staff from three dementia care units in Brisbane, Australia.

Major findings: Four themes were identified: role definition, relationships, workplace environment, and workforce issues. Although the findings highlight the importance of peer support for staff when managing difficult situations, questions regarding the quality of peer support and its impact on care provision were raised.

Conclusions: Dementia units are complex systems with well-motivated and educated staff contributing to the effectiveness of the care. An understanding of care staff, perceptions of their role and its effects on care practices can help to identify appropriate support structures and training strategies, thereby improving job satisfaction for staff and quality of life for the residents with dementia.
Following What People Think We Should Do Versus What People Actually Do
Authors: Kredentser Maia S. , Fabrigar Leandre R. , Smith Steven M. , Fulton Kimberly
Published: September 2011

This study explored cognitive elaboration as a moderator of the impact of injunctive and descriptive normative messages on behavioral intentions. Participants ( N = 246) received a message advocating a student health program that stressed either descriptive norms or injunctive norms under conditions of low elaboration or high elaboration and then responded to a series of behavioral intention questions. To determine whether the effects of type of normative message and elaboration varied across personality traits, participants’ level of self-monitoring and extraversion were measured 1–6 months prior to the experimental session. Analyses revealed a 2-way interaction between message type and elaboration, suggesting that descriptive messages were more successful under low-elaboration conditions, whereas injunctive messages were more successful under high-elaboration conditions. This 2-way interaction was not qualified by a 3-way interaction among extraversion, message type, and elaboration or a 3-way interaction among self-monitoring, message type, and elaboration.
Age-related macular degeneration: current treatment and future options
Authors: Moutray Tanya , Chakravarthy Usha
Published: September 2011

Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.
BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium
Authors: Helbing Thomas , Rothweiler René , Ketterer Elena , Goetz Lena , Heinke Jennifer , Grundmann Sebastian , Duerschmied Daniel , Patterson Cam , Bode Christoph , Moser Martin
Published: September 2011

The endothelium plays a pivotal role in vascular inflammation. Here we study bone morphogenetic protein (BMP) signaling in endothelial inflammation and in particular the role of BMPER, an extracellular BMP modulator that is important in vascular development and angiogenesis. Using the BMP antagonist dorsomorphin or BMP2 as an agonist we show that BMP signaling is essential for the inflammatory response of vascular endothelial cells as demonstrated by intravital microscopy. We found that BMPER is decreased in inflammation similar to vascular protective genes like KLF2 and eNOS. Using in vitro and in vivo models we show that BMPER is down-regulated through the TNFα-NFκB-KLF2 signaling pathway. Functionally, lack of BMPER induced by siRNA or in BMPER+/− mice confers a proinflammatory endothelial phenotype with reduced eNOS levels and enhanced expression of adhesion molecules leading to increased leukocyte adhesion and extravasation in ex vivo and in vivo experiments. Vice versa, addition of BMPER exerts endothelium protective functions and antagonizes TNFα induced inflammation. Mechanistically, we demonstrate that these effects of BMPER are dependent on BMP signaling because of enhanced NFκB activity. In conclusion, the BMP modulator BMPER is a new protective regulator of vascular inflammation that modulates leukocyte adhesion and migration in vitro and in vivo.
The impact of Fc-γ receptor polymorphisms in elderly patients with diffuse large B-cell lymphoma treated with CHOP with or without rituximab
Authors: Ahlgrimm Manfred , Pfreundschuh Michael , Kreuz Markus , Regitz Evi , Preuss Klaus-Dieter , Bittenbring Joerg
Published: September 2011

Fcγ receptor (FcγR) polymorphisms have been shown to affect rituximab-mediated antibody-dependent cellular cytotoxicity. Of 512 patients with diffuse large B-cell lymphoma treated in the RICOVER-60 trial, carriers of FcγRIII 158 valine homozygous receptors (V/V) presented with a slightly decreased incidence of B-symptoms (158 V/V: 26%, V/F: 35%, phenylalanine receptors [F/F]: 42%; P = .037). Survival curves of all FcγR single nucleotide polymorphisms were superimposable after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); but after CHOP with rituximab (R-CHOP), event-free survival (EFS) and progression-free survival (PFS), but not overall survival, of FcγRIIIa 158 F/F had a trend to be lower than those of 158 V/F and 158 V/V: 3-year EFS: FcγRIIIa 158 F/F: 64.5%, 158 V/F: 70.2%, 158 V/V: 76.9% (log-rank test: P = .224 F/F vs V/V; P = .285 F/F vs V/F + V/V); 3-year PFS: FcγRIIIa 158 F/F: 68.3%, V/F: 76.1%, V/V: 80.5% (log-rank test: P = .233 for F/F vs V/V; P = .185 for F/F vs V/F + V/V). By multivariate analysis adjusting for International Prognostic Index factors, relative risk of F/F compared with V/F plus V/V was 1.80 (P = .052) for PFS and 1.55 (P = .120) for EFS. The interaction of R-CHOP, but not CHOP with FcγRIIIa polymorphisms, indicates a window of opportunity for CD20 antibodies designed to mediate enhanced antibody-dependent cellular cytotoxicity.
ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor
Authors: Torrano Veronica , Procter Julia , Cardus Penny , Greaves Mel , Ford Anthony M.
Published: September 2011

ETV6-RUNX1 gene fusion is usually an early, prenatal event in childhood acute lymphoblastic leukemia (ALL). Transformation results in the generation of a persistent (> 14 years) preleukemic clone, which postnatally converts to ALL after the acquisition of necessary secondary genetic alterations. Many cancer cells show some expression of the erythropoietin receptor (EPOR) gene, although the “functionality” of any EPOR complexes and their relevant signaling pathways in nonerythroid cells has not been validated. EPOR mRNA is selectively and ectopically expressed in ETV6-RUNX1+ ALL, but the presence of a functional EPOR on the cell surface and its role in leukemogenesis driven by ETV6-RUNX1 remains to be identified. Here, we show that ETV6-RUNX1 directly binds the EPOR promoter and that expression of ETV6-RUNX1 alone in normal pre-B cells is sufficient to activate EPOR transcription. We further reveal that murine and human ETV6-RUNX1+ cells expressing EPOR mRNA have EPO ligand binding activity that correlates with an increased cell survival through activation of the JAK2-STAT5 pathway and up-regulation of antiapoptotic BCL-XL. These data support the contention that ETV6-RUNX1 directly activates ectopic expression of a functional EPOR and provides cell survival signals that may contribute critically to persistence of covert premalignant clones in children.
Low telomerase activity in CD4+ regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation
Authors: Kawano Yutaka , Kim Haesook T. , Matsuoka Ken-ichi , Bascug Gregory , McDonough Sean , Ho Vincent T. , Cutler Corey , Koreth John , Alyea Edwin P. , Antin Joseph H. , Soiffer Robert J. , Ritz Jerome
Published: September 2011

CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the control of chronic graft-versus-host disease (cGVHD). In this study, we examined telomere length and telomerase activity of Treg and conventional CD4+ T cells (Tcon) in 61 patients who survived more than 2 years after allogeneic hematopoietic stem cell transplantation. Cell proliferation and expression of Bcl-2 were also measured in each subset. Treg telomere length was shorter and Treg telomerase activity was increased compared with Tcon (P < .0001). After transplantation, Treg were also more highly proliferative than Tcon (P < .0001). Treg number, telomerase activity, and expression of Bcl-2 were each inversely associated with severity of cGVHD. These data indicate that activation of telomerase is not sufficient to prevent telomere shortening in highly proliferative Treg. However, telomerase activation is associated with increased Bcl-2 expression and higher Treg numbers in patients with no or mild cGVHD. In contrast, patients with moderate or severe cGVHD have fewer Treg with lower levels of telomerase activity and Bcl-2 expression. These results suggest that failure to activate Treg telomerase may restrict proliferative capacity and increase apoptotic susceptibility, resulting in the loss of peripheral tolerance and the development of cGVHD.
Inhibition of IL-32 activation by α-1 antitrypsin suppresses alloreactivity and increases survival in an allogeneic murine marrow transplantation model
Authors: Marcondes A. Mario , Li Xiang , Tabellini Laura , Bartenstein Matthias , Kabacka Julia , Sale George E. , Hansen John A. , Dinarello Charles A. , Deeg H. Joachim
Published: September 2011

Interleukin (IL)–32 was originally identified in natural killer cells and IL-2–activated human T lymphocytes. As T cells are activated in allogeneic transplantation, we determined the role of IL-32 in human mixed lymphocyte cultures (MLCs) and GVHD. In allogeneic MLCs, IL-32 increased two-fold in responding T cells, accompanied by five-fold increases of TNFα, IL-6, and IL-8. After allogeneic hematopoietic cell transplantation, IL-32 mRNA levels in blood leukocytes were statistically significantly higher in patients with acute GVHD (n = 10) than in serial samples from patients who did not develop acute GVHD (n = 5; P = .02). No significant changes in IL-32 levels were present in patients with treated (n = 14) or untreated (n = 8) chronic GVHD, compared with healthy controls (n = 8; P = .5, and P = .74, respectively). As IL-32 is activated by proteinase-3 (PR3), we determined the effect of the serine protease inhibitor α-1 antitrypsin (AAT) on IL-32 levels and showed suppression of IL-32 and T-lymphocyte proliferation in MLCs. In an MHC-minor antigen disparate murine transplant model, preconditioning and postconditioning treatment with AAT resulted in attenuation or prevention of GVHD and superior survival compared with albumin-treated controls (80% vs 44%; P = .04). These findings suggest that AAT modulates immune and inflammatory functions and may represent a novel approach to prevent or treat GVHD.
Pivotal trial with plant cell–expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease
Authors: Zimran Ari , Brill-Almon Einat , Chertkoff Raul , Petakov Milan , Blanco-Favela Francisco , Muñoz Eduardo Terreros , Solorio-Meza Sergio E. , Amato Dominick , Duran Gloria , Giona Fiorina , Heitner Rene , Rosenbaum Hanna , Giraldo Pilar , Mehta Atul , Park Glen , Phillips Mici , Elstein Deborah , Altarescu Gheona , Szleifer Mali , Hashmueli Sharon , Aviezer David
Published: September 2011

Taliglucerase alfa (Protalix Biotherapeutics, Carmiel, Israel) is a novel plant cell–derived recombinant human β-glucocerebrosidase for Gaucher disease. A phase 3, double-blind, randomized, parallel-group, comparison-dose (30 vs 60 U/kg body weight/infusion) multinational clinical trial was undertaken. Institutional review board approvals were received. A 9-month, 20-infusion trial used inclusion/exclusion criteria in treatment-naive adult patients with splenomegaly and thrombocytopenia. Safety end points were drug-related adverse events: Ab formation and hypersensitivity reactions. Primary efficacy end point was reduction in splenic volume measured by magnetic resonance imaging. Secondary end points were: changes in hemoglobin, hepatic volume, and platelet counts. Exploratory parameters included biomarkers and bone imaging. Twenty-nine patients (11 centers) completed the protocol. There were no serious adverse events; drug-related adverse events were mild/moderate and transient. Two patients (6%) developed non-neutralizing IgG Abs; 2 other patients (6%) developed hypersensitivity reactions. Statistically significant spleen reduction was achieved at 9 months: 26.9% (95% confidence interval [CI]: −31.9, −21.8) in the 30-unit dose group and 38.0% (95% CI: −43.4, −32.8) in the 60-unit dose group (both P < .0001); and in all secondary efficacy end point measures, except platelet counts at the lower dose. These results support safety and efficacy of taliglucerase alfa for Gaucher disease. This study was registered at www.clinicaltrials.gov as NCT00376168.
WebMGA: a customizable web server for fast metagenomic sequence analysis
Authors: Wu Sitao , Zhu Zhengwei , Fu Liming , Niu Beifang , Li Weizhong
Published: September 2011

Background

The new field of metagenomics studies microorganism communities by culture-independent sequencing. With the advances in next-generation sequencing techniques, researchers are facing tremendous challenges in metagenomic data analysis due to huge quantity and high complexity of sequence data. Analyzing large datasets is extremely time-consuming; also metagenomic annotation involves a wide range of computational tools, which are difficult to be installed and maintained by common users. The tools provided by the few available web servers are also limited and have various constraints such as login requirement, long waiting time, inability to configure pipelines etc.

Results

We developed WebMGA, a customizable web server for fast metagenomic analysis. WebMGA includes over 20 commonly used tools such as ORF calling, sequence clustering, quality control of raw reads, removal of sequencing artifacts and contaminations, taxonomic analysis, functional annotation etc. WebMGA provides users with rapid metagenomic data analysis using fast and effective tools, which have been implemented to run in parallel on our local computer cluster. Users can access WebMGA through web browsers or programming scripts to perform individual analysis or to configure and run customized pipelines. WebMGA is freely available at http://weizhongli-lab.org/metagenomic-analysis.

Conclusions

WebMGA offers to researchers many fast and unique tools and great flexibility for complex metagenomic data analysis.
Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type
Authors: Morey Marcos , Castro-Feijóo Lidia , Barreiro Jesús , Cabanas Paloma , Pombo Manuel , Gil Marta , Bernabeu Ignacio , Díaz-Grande José M , Rey-Cordo Lourdes , Ariceta Gema , Rica Itxaso , Nieto José , Vilalta Ramón , Martorell Loreto , Vila-Cots Jaime , Aleixandre Fernando , Fontalba Ana , Soriano-Guillén Leandro , García-Sagredo José M , García-Miñaur Sixto , Rodríguez Berta , Juaristi Saioa , García-Pardos Carmen , Martínez-Peinado Antonio , Millán José M , Medeira Ana , Moldovan Oana , Fernandez Angeles , Loidi Lourdes
Published: September 2011

Background

Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.

Methods

Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.

Results

Mutations in the PHEX gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).

Conclusions

PHEX gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious PHEX mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of mutation might predict the XLHR phenotype severity.
A life course approach to injury prevention: a "lens and telescope" conceptual model
Authors: Hosking Jamie , Ameratunga Shanthi , Morton Susan , Blank Danilo
Published: September 2011

Background

Although life course epidemiology is increasingly employed to conceptualize the determinants of health, the implications of this approach for strategies to reduce the burden of injuries have received little recognition to date.

Methods

The authors reviewed core injury concepts and the principles of the life course approach. Based on this understanding, a conceptual model was developed, to provide a holistic view of the mechanisms that underlie the accumulation of injury risk and their consequences over the life course.

Results

A "lens and telescope" model is proposed that particularly draws on (a) the extended temporal dimension inherent in the life course approach, with links between exposures and outcomes that span many years, or even generations, and (b) an ecological perspective, according to which the contexts in which individuals live are critical, as are changes in those contexts over time.

Conclusions

By explicitly examining longer-term, intergenerational and ecological perspectives, life course concepts can inform and strengthen traditional approaches to injury prevention and control that have a strong focus on proximal factors. The model proposed also serves as a tool to identify intervention strategies that have co-benefits for other areas of health.
Growth of vertically aligned ZnO nanorods using textured ZnO films
Authors: Solís-Pomar Francisco , Martínez Eduardo , Meléndrez Manuel F , Pérez-Tijerina Eduardo
Published: September 2011

A hydrothermal method to grow vertical-aligned ZnO nanorod arrays on ZnO films obtained by atomic layer deposition (ALD) is presented. The growth of ZnO nanorods is studied as function of the crystallographic orientation of the ZnO films deposited on silicon (100) substrates. Different thicknesses of ZnO films around 40 to 180 nm were obtained and characterized before carrying out the growth process by hydrothermal methods. A textured ZnO layer with preferential direction in the normal c-axes is formed on substrates by the decomposition of diethylzinc to provide nucleation sites for vertical nanorod growth. Crystallographic orientation of the ZnO nanorods and ZnO-ALD films was determined by X-ray diffraction analysis. Composition, morphologies, length, size, and diameter of the nanorods were studied using a scanning electron microscope and energy dispersed x-ray spectroscopy analyses. In this work, it is demonstrated that crystallinity of the ZnO-ALD films plays an important role in the vertical-aligned ZnO nanorod growth. The nanorod arrays synthesized in solution had a diameter, length, density, and orientation desirable for a potential application as photosensitive materials in the manufacture of semiconductor-polymer solar cells.

PACS

61.46.Hk, Nanocrystals; 61.46.Km, Structure of nanowires and nanorods; 81.07.Gf, Nanowires; 81.15.Gh, Chemical vapor deposition (including plasma-enhanced CVD, MOCVD, ALD, etc.)
A relaxed hybrid steepest descent method for common solutions of generalized mixed equilibrium problems and fixed point problems
Authors: Onjai-uea Nawitcha , Jaiboon Chaichana , Kumam Poom
Published: September 2011

In the setting of Hilbert spaces, we introduce a relaxed hybrid steepest descent method for finding a common element of the set of fixed points of a nonexpansive mapping, the set of solutions of a variational inequality for an inverse strongly monotone mapping and the set of solutions of generalized mixed equilibrium problems. We prove the strong convergence of the method to the unique solution of a suitable variational inequality. The results obtained in this article improve and extend the corresponding results.

AMS (2000) Subject Classification: 46C05; 47H09; 47H10.
PTH Ablation Ameliorates the Anomalies of Fgf23-Deficient Mice by Suppressing the Elevated Vitamin D and Calcium Levels
Authors: Yuan Quan , Sitara Despina , Sato Tadatoshi , Densmore Michael , Saito Hiroaki , Schüler Christine , Erben Reinhold G. , Lanske Beate
Published: September 2011

Fibroblast growth factor 23 (FGF23) is a key regulator of mineral ion homeostasis. Genetic ablation of Fgf23 in mice leads to severe biochemical disorders including elevated serum 1,25-dihydroxyvitamin D [1,25(OH)2D], hypercalcemia, hyperphosphatemia, and marked decreased PTH levels. Because PTH stimulates 1,25(OH)2D production and increases serum calcium levels, we hypothesized that ablation of PTH from the Fgf23 knockout (Fgf23−/−) mice could suppress these affects, thus ameliorating the soft tissue and skeletal anomalies in these animals. In this study, we generated a genetic mouse model with dual ablation of the Fgf23/PTH genes. The data show that deletion of PTH does suppress the markedly higher serum 1,25(OH)2D and calcium levels observed in Fgf23−/− mice and results in much larger, heavier, and more active double-knockout mice with improved soft tissue and skeletal phenotypes. On the contrary, when we infused PTH (1–34) peptide into Fgf23−/− mice using osmotic minipumps, serum 1,25(OH)2D and calcium levels were increased even further, leading to marked reduction in trabecular bone. These results indicate that PTH is able to modulate the anomalies of Fgf23−/− mice by controlling serum 1,25(OH)2D and calcium levels.
Changes in BiP availability reveal hypersensitivity to acute endoplasmic reticulum stress in cells expressing mutant huntingtin
Authors: Lajoie Patrick , Snapp Erik L.
Published: September 2011

Huntington's disease (HD) is caused by expanded glutamine repeats within the huntingtin (Htt) protein. Mutant Htt (mHtt) in the cytoplasm has been linked to induction of the luminal endoplasmic reticulum (ER) stress pathway, the unfolded protein response (UPR). How mHtt impacts the susceptibility of the ER lumen to stress remains poorly understood. To investigate molecular differences in the ER in cells expressing mHtt, we used live-cell imaging of a sensitive reporter of the misfolded secretory protein burden, GFP fused to the ER chaperone BiP (also known as GRP78), which decreases in mobility as it binds increasing amounts of misfolded proteins. Striatal neurons expressing full-length mHtt showed no differences in BiP–GFP mobility and no evidence of UPR activation compared with wild-type cells at steady state. However, mHtt-expressing cells were acutely sensitive to misfolded secretory proteins. Treatment with ER stressors, tunicamycin or DTT, rapidly decreased BiP–GFP mobility in mHtt striatal cells and accelerated UPR activation compared with wild-type cells. mHtt-expressing cells exhibited decreased misfolded protein flux as a result of ER associated degradation (ERAD) dysfunction. Furthermore, UPR-adapted mHtt cells succumbed to misfolded protein stresses that could be tolerated by adapted wild-type cells. Thus, mHtt expression impairs misfolded secretory protein turnover, decreases the ER stress threshold, and increases cell vulnerability to insults.
Fatigue-related adaptations in muscle coordination during a cyclic exercise in humans
Authors: Turpin Nicolas A. , Guével Arnaud , Durand Sylvain , Hug François
Published: September 2011

Muscle fatigue is an exercise-induced reduction in the capability of a muscle to generate force. A possible strategy to counteract the effects of fatigue is to modify muscle coordination. We designed this study to quantify the effect of fatigue on muscle coordination during a cyclic exercise involving numerous muscles. Nine human subjects were tested during a constant-load rowing exercise (mean power output: 217.9±32.4 W) performed until task failure. The forces exerted at the handle and the foot-stretcher were measured continuously and were synchronized with surface electromyographic (EMG) signals measured in 23 muscles. In addition to a classical analysis of individual EMG data (EMG profile and EMG activity level), a non-negative matrix factorization algorithm was used to identify the muscle synergies at the start and the end of the test. Among the 23 muscles tested, 16 showed no change in their mean activity level across the rowing cycle, five (biceps femoris, gluteus maximus, semitendinosus, trapezius medius and vastus medialis) showed a significant increase and two (gastrocnemius lateralis and longissimus) showed a significant decrease. We found no change in the number of synergies during the fatiguing test, i.e. three synergies accounted for more than 90% of variance accounted for at the start (92.4±1.5%) and at the end (91.0±1.8%) of the exercise. Very slight modifications at the level of individual EMG profiles, synergy activation coefficients and muscle synergy vectors were observed. These results suggest that fatigue during a cyclic task preferentially induces an adaptation in muscle activity level rather than changes in the modular organization of the muscle coordination.
Epirubicin, Oxaliplatin, and Capecitabine Regimen for Gastric and Esophageal Cancer
Authors: Waddell J. Aubrey , Solimando Dominic A.
Published: September 2011

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Remote Order Entry Services: Providing 24-Hour Pharmaceutical Care for Small to Medium Sized Hospitals
Authors: Mango Michael D. , Mabe Don M.
Published: September 2011

Purpose

In the last few years, The Joint Commission (TJC) has strongly recommended that hospitals provide 24-hour pharmacy services. Many small to medium sized hospitals have insufficient workload and/or lack the financial resources to justify 24-hour pharmacy services. When a pharmacy does not provide 24-hour pharmacy services, it must provide a retrospective review of medication orders. Carolinas Healthcare System (CHS) faced the challenge of economically providing 24-hour pharmaceutical care in smaller to medium size hospitals by developing a remote order entry service (ROES).

This article describes the process of implementing an ROES and the technology that is involved, including physician order transmittal, pharmacy information systems, communication between facilities, distribution of pharmaceuticals, and clinical pharmacy services. The financial and pharmaceutical service benefits are illustrated.

Conclusion

ROES has proven to be an effective method that allows small to medium sized hospitals access to 24-hour pharmaceutical care in a fiscally responsible manner.
Use of Prasugrel in a Patient with Clopidogrel Hypersensitivity
Authors: Peppard Sarah R , Held-Godgluck Bethanne M , Beddingfield Richard
Published: September 2011

Objective:

To report a case of successful use of prasugrel following percutaneous coronary intervention with placement of a bare metal stent in a patient with a documented hypersensitivity reaction to clopidogrel.

Case Summary:

A 61-year-old male with a history of coronary artery disease with coronary stent placement presented with ST-elevation myocardial infarction. The patient had developed Stephens-Johnson syndrome 6 years earlier following Clopidogrel administration, characterized by erythematous plaques and subsequent desquamation of the hands and feet; Clopidogrel was discontinued and he was subsequently treated with ticlopidine in addition to aspirin. The third-generation thienopyridine prasugrel was initiated as a therapeutic alternative to Clopidogrel after placement of a bare metal stent; a 60-mg dose was administered after extubation, followed by 10 mg/day. No signs of allergic reaction were observed in the days, weeks, and months following administration.

Discussion:

Thienopyridines, specifically Clopidogrel, are the standard of care for prevention of coronary stent thrombosis; however, there are few data available on cross-hypersensitivity between these agents. One study demonstrated that 27% of patients who developed an allergic or hematologic reaction to Clopidogrel developed a similar reaction to ticlopidine. Other therapeutic options for patients with Clopidogrel hypersensitivity who are undergoing a percutaneous coronary intervention with stent placement include Clopidogrel desensitization, warfarin plus aspirin, cilostazol, ticagrelor, and ticlopidine. However, these options are limited by efficacy and/or toxicity. With its approval in 2009, prasugrel has become a potential treatment option.

Conclusions:

Prasugrel may be considered a therapeutic alternative in some patients allergic or intolerant to Clopidogrel, but additional data are warranted to make a strong conclusion.
A new method for removing microflora from macroalgal surfaces: an important step for natural product discovery
Authors: Kientz Betty , Thabard Marie , Cragg Simon M. , Pope Josephine , Hellio Claire
Published: September 2011

Numerous marine organisms, including macroalgae, produce bioactive compounds. As chemical extraction processes do not distinguish between compounds originating from the alga and its associated microflora, a key step immediately prior to isolation of molecules, is elimination of epibionts from the alga studied. In chemical, ecological and biotechnological contexts, a clear identification of the source organism, when symbiotic interactions occurs, is crucial. We aimed to improve understanding of specific secondary metabolite production by macroalgae through development of a metho-dology for removing microbial epibionts immediately prior to chemical extraction without damaging algal cell surfaces (to avoid extraction of endogenous macroalgal compounds at this stage). Various solutions were tested: non-polar solvents (dichloromethane and hexane), alcohols (methanol, ethanol and isopropanol), oxidants (sodium hypochlorite, hydrogen peroxide and iodine) and a natural product (tea tree oil) at various concentrations and contact times. Five macroalgal species were employed: Chondrus crispus, Fucus serratus, Palmaria palmata, Saccharina latissima and Ulva lactuca. Scanning electron microscopy was used to evaluate the surface integrity. The best epibiont removal rate without damaging tissue was obtained with mixtures of ethanol (40–50%) and sodium hypochlorite (1%). Interestingly, macroalgal moisture content influenced treatment efficacy.
To mix or not to mix venous blood samples collected in vacuum tubes?
Authors: Parenmark Anna , Landberg Eva
Published: September 2011

There are recommendations to mix venous blood samples by inverting the tubes immediately after venipuncture. Though mixing allows efficient anticoagulation in plasma tubes and fast initiation of coagulation in serum tubes, the effect on laboratory analyses and risk of haemolysis has not been thoroughly evaluated.

Venous blood samples were collected by venipuncture in vacuum tubes from 50 patients (10 or 20 patients in each group). Four types of tubes and 18 parameters used in routine clinical chemistry were evaluated. For each patient and tube, three types of mixing strategies were used: instant mixing, no mixing and 5 min of rest followed by mixing.

Most analyses did not differ significantly in samples admitted to different mixing strategies. Plasma lactate dehydrogenase and haemolysis index showed a small but significant increase in samples omitted to instant mixing compared to samples without mixing. However, in one out of twenty non-mixed samples, activated partial thromboplastin time was seriously affected.

These results indicate that mixing blood samples after venipuncture is not mandatory for all types of tubes. Instant mixing may introduce interference for those analyses susceptible to haemolysis. However, tubes with liquid-based citrate buffer for coagulation testing should be mixed to avoid clotting.
Empirical models for radial and tangential fibre width in tree rings of Norway spruce in north-western Europe
Authors: Franceschini Tony , Lundqvist Sven-Olof , Bontemps Jean-Daniel , Grahn Thomas , Olsson Lars , Evans Robert , Leban Jean-Michel
Published: September 2011

Tracheid dimensions influence the quality of wood and that of pulp and paper. Both between- and within-ring variations are influenced by tree developmental stage, site, genetics, and forest management. To contribute to the knowledge in this regard, the radial and tangential tracheid dimensions on Norway spruce, defined as the lumens and double cell wall thickness, have been measured using a SilviScan device. Namely, 4947 annual rings from 35 trees from plantations in France, Norway, and Sweden were examined. Mixed-effects models were constructed concerning the radial and tangential tracheid widths for the total ring and in three within-ring compartments – earlywood (EW), transition wood (TW), and latewood (LW) – as functions of age, radius, height in the tree, and growth rate. Between-site and between-tree variations were also considered. The mean radial tracheid width was 34.2 μm (EW), 29.9 μm (TrW), and 22.1 μm (LW). The tangential tracheid width was on average 30.1 μm in all compartments. The radial and tangential tracheid widths in the rings and compartments increased from the pith to the bark and decreased with greater growth rates. Within a given ring, both properties decreased with height in the tree. The fixed part of the models of the radial tracheid width accounted for 68% (EW), 45% (TW), and 33% (LW) while for the models of the tangential fibre width it accounted for 42% of the variation in all compartments. Climate or hydraulic maintenance was hypothesised to be responsible for the variation of the radial tracheid width.
Qualitätsentwicklung in der sprachpraktischen Ausbildung der Studiengänge fremdsprachlicher Fächer im Jahr 2010
Authors: Meißner Franz-Joseph
Published: September 2011

In the light of the current situation, the following paper discusses some central questions related to foreign language training so far as university students of modern language subjects are concerned. This affects the education of teachers as well as of specialists who combine particular foreign language skills with other academic competences. What do these students need in their future professional fields that should be learned in foreign language courses? What are their demands concerning foreign language instruction? It goes without saying that these questions are related to much more than language and languages. Thus teachers need didactical and methodical knowledge, knowledge about test construction, self-assessment and computer literacies. The importance of oral communication has constantly increased during the last forty years, but university courses often still focus writing. And what about translation? What are the criteria for good language teaching?
Differential BOLD Activity Associated with Subjective and Objective Reports during “Blindsight” in Normal Observers
Authors: Hesselmann Guido , Hebart Martin , Malach Rafael
Published: September 2011

The study of conscious visual perception invariably necessitates some means of report. Report can be either subjective, i.e., an introspective evaluation of conscious experience, or objective, i.e., a forced-choice discrimination regarding different stimulus states. However, the link between report type and fMRI-BOLD signals has remained unknown. Here we used continuous flash suppression to render target images invisible, and observed a long-lasting dissociation between subjective report of visibility and human subjects' forced-choice localization of targets (“blindsight”). Our results show a robust dissociation between brain regions and type of report. We find subjective visibility effects in high-order visual areas even under equal objective performance. No significant BOLD difference was found between correct and incorrect trials in these areas when subjective report was constant. On the other hand, objective performance was linked to the accuracy of multivariate pattern classification mainly in early visual areas. Together, our data support the notion that subjective and objective reports tap cortical signals of different location and amplitude within the visual cortex.
Default Mode of Brain Function in Monkeys
Authors: Mantini Dante , Gerits Annelis , Nelissen Koen , Durand Jean-Baptiste , Joly Olivier , Simone Luciano , Sawamura Hiromasa , Wardak Claire , Orban Guy A. , Buckner Randy L. , Vanduffel Wim
Published: September 2011

Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.
Abnormalities in the Climbing Fiber-Purkinje Cell Circuitry Contribute to Neuronal Dysfunction inATXN1[82Q] Mice
Authors: Barnes Justin A. , Ebner Blake A. , Duvick Lisa A. , Gao Wangcai , Chen Gang , Orr Harry T. , Ebner Timothy J.
Published: September 2011

One fundamental unanswered question in the field of polyglutamine diseases concerns the pathophysiology of neuronal dysfunction. Is there dysfunction in a specific neuronal population or circuit initially that contributes the onset of behavioral abnormalities? This study used a systems-level approach to investigate the functional integrity of the excitatory cerebellar cortical circuitryin vivofrom several transgenicATXN1mouse lines. We tested the hypotheses that there are functional climbing fiber (CF)–Purkinje cell (PC) and parallel fiber (PF)–PC circuit abnormalities using flavoprotein autofluorescence optical imaging and extracellular field potential recordings. In early-symptomatic and symptomatic animals expressingATXN1[82Q], there is a marked reduction in PC responsiveness to CF activation. Immunostaining of vesicular glutamate transporter type 2 demonstrated a decrement in CF extension on PC dendrites in symptomaticATXN1[82Q] mice. In contrast, responses to PF stimulation were relatively normal. Importantly, the deficits in CF–PC synaptic transmission required expression of pathogenic ataxin-1 (ATXN1[82Q]) and for its entrance into the nucleus of PCs. Loss of endogenous mouse Atxn1 had no discernible effects. Furthermore, the abnormalities in CF–PC synaptic transmission were ameliorated when mutant transgene expression was prevented during postnatal cerebellar development. The results demonstrate the preferential susceptibility of the CF–PC circuit to the effects of ATXN1[82Q]. Further, this deficit likely contributes to the abnormal motor phenotype ofATXN1[82Q] mice. For polyglutamine diseases generally, the findings support a model whereby specific neuronal circuits suffer insults that alter function before cell death.
What Do We Know About the Iconic System CH3 + CH3 + M ↔ C2H6 + M?
Authors: Golden David M.
Published: September 2011

A comparison of representative experimental data [296<T/K<1920; 103<P/atm<101] and “theory” reveals some of the strengths and weaknesses of current understanding of the title reaction. The available data has been reconciled with a theoretically derived value of the high-pressure rate constant for methyl radical combination using a hindered-Gorin transition state using the Multiwell suite of codes.