bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased frequency of metabolic syndrome among Vietnamese women with early rheumatoid arthritis: a cross-sectional study
Authors: Dao Hanh-Hung , Do Quan-Trung , Sakamoto Junichi
Published: January 2011

Introduction

Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease, and this occurs early in the disease process. The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in RA; however, little information is available regarding MetS in early RA. We aimed to identify the prevalence of MetS and to determine the potential factors associated with the presence of MetS in Vietnamese women with early RA.

Methods

A total of 105 consecutive women with early RA (disease duration ≤3 years) and 105 age-matched healthy women were checked for MetS according to six MetS definitions (Joint Consensus, International Diabetes Federation, National Cholesterol Education Program 2004 and 2001, European Group for Study of Insulin Resistance, and World Health Organization). Multivariate logistic regression models were constructed to determine independent predictors of MetS in women with RA.

Results

Prevalence of MetS varied from 16.2% to 40.9% according to the definitions used in women with RA, and was higher (P < 0.001) than in healthy controls (from 10.5% to 22.9%). Among individual components of MetS, differences between women with RA and controls were observed for hypertension (P < 0.001), low high density lipoprotein-cholesterol (HDL-C) levels (P < 0.001), and abdominal obesity (P = 0.019). After adjusting for age and physical activity, higher erythrocyte sedimentation rate (ESR) (odds ratios (OR) = 1.516, 95% confidence interval (CI): 1.073 to 3.195, P = 0.042), disease activity score (DAS28) (OR = 1.736, 95% CI: 1.293 to 2.786, P = 0.019), health assessment questionnaire (HAQ) score (OR = 1.583, 95% CI: 1.195 to 2.367, P = 0.035), and less methotrexate use (OR = 0.736, 95% CI: 0.547 to 0.962, P = 0.024) remained significant independent predictors of the presence of MetS in women with RA.

Conclusions

Women with early RA already had higher prevalence of MetS compared with healthy controls. Higher systemic inflammatory marker, disease activity and disability scores, and less methotrexate use were independent predictors associated with the presence of MetS in women with early RA. These findings suggest that physicians should screen for MetS in women with early RA to control its components and therefore reduce their risk of cardiovascular diseases.
Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study
Authors: Bartelds Geertje M , de Groot Els , Nurmohamed Michael T , Hart Margreet HL , van Eede Peter H , Wijbrandts Carla A , Crusius Jakob BA , Dijkmans Ben AC , Tak Paul Peter , Aarden Lucien , Wolbink Gerrit J
Published: January 2011

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.
Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model
Authors: García Samuel , Forteza Jerónimo , López-Otin Carlos , Gómez-Reino Juan J , González Antonio , Conde Carmen
Published: January 2011

Introduction

Rheumatoid arthritis is an autoimmune disease in which joint inflammation leads to progressive cartilage and bone erosion. Matrix metalloproteinases (MMPs) implicated in homeostasis of the extracellular matrix play a central role in cartilage degradation. However, the role of specific MMPs in arthritis pathogenesis is largely unknown. The aim of the present study was to investigate the role of Mmp-8 (collagenase-2) in an arthritis model.

Methods

Arthritis was induced inMmp8-deficient and wildtype mice by K/BxN serum transfer. Arthritis severity was measured by a clinical index and ankle sections were scored for synovial inflammation, cartilage damage and bone erosion. cDNA microarray analysis, real-time PCR and western blot were performed to identify differential changes in gene expression between mice lackingMmp8and controls.

Results

Mmp8deficiency increased the severity of arthritis, although the incidence of disease was similar in control and deficient mice. Increased clinical score was associated with exacerbated synovial inflammation and bone erosion. We also found that the absence ofMmp8led to increased expression ofIL-1β, pentraxin-3 (PTX3) and prokineticin receptor 2 (PROKR2) in arthritic mice joints.

Conclusions

Lack of Mmp-8 is accompanied by exacerbated synovial inflammation and bone erosion in the K/BxN serum-transfer arthritis model, indicating that this Mmp has a protective role in arthritis.
Validating English- and Spanish-language patient-reported outcome measures in underserved patients with rheumatic disease
Authors: Wallen Gwenyth R , Middleton Kimberly R , Rivera-Goba Migdalia V , Mittleman Barbara B
Published: January 2011

Introduction

Rheumatic diseases are among the most common and debilitating health problems in the United States. These diseases are chronic, can result in severe decrements of physical and psychosocial functioning and affect patients' overall quality of life. A consensus regarding the best patient outcomes to be measured in randomized, controlled trials and prospective natural history studies is essential to provide best estimates of efficacy and safety of interventions across diverse patient populations.

Methods

Face-to-face English- and Spanish-language cognitive interviews were conducted among urban Hispanic and African American patients with rheumatic disease to develop a questionnaire booklet. Six measures validating patient-reported outcomes were included: the Arthritis Self-Efficacy Scale, the Stanford Health Assessment Questionnaire Disability Index, the Wong-Baker Faces Pain Scale, the Short Acculturation Scale, the Center for Epidemiologic Studies Depression Scale and the Inventory of Complementary and Alternative Medicine Practices. A sample of patients (n = 15) attending the National Institute of Arthritis and Musculoskeletal and Skin Diseases Community Health Center participated in the initial interviews. Revised measures were further tested for reliability in a separate sample of patients (n = 109) upon enrollment at the health center.

Results

Cognitive interviews provided feedback for questionnaire modifications and methods to enhance content validity and data quality, including discarding redundant questions, providing visual aids and concrete examples when appropriate and increasing the use of racially and ethnically concordant interviewers. The cognitive interviews further elucidated that some contextual assumptions and language usage in the original questionnaires may not have taken each respondent's environmental and sociocultural context into consideration. Internal reliability for previously tested measures remained high (Cronbach's α = 0.87-0.94).

Conclusions

Cognitive interviewing techniques are useful in a diverse sample of racial and ethnic minority patients with rheumatic disease as a method to assess the content validity of the specific outcome measures selected. The data collection approaches and methods described here ultimately enhance data quality. Vigilance is required in the selection of outcome measures in studies or in practice, particularly with each new language translation and/or culturally unique or diverse sample.
Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet
Authors: Barbui Tiziano , Barosi Giovanni , Birgegard Gunnar , Cervantes Francisco , Finazzi Guido , Griesshammer Martin , Harrison Claire , Hasselbalch Hans Carl , Hehlmann Rudiger , Hoffman Ronald , Kiladjian Jean-Jacques , Kröger Nicolaus , Mesa Ruben , McMullin Mary F. , Pardanani Animesh , Passamonti Francesco , Vannucchi Alessandro M. , Reiter Andreas , Silver Richard T. , Verstovsek Srdan , Tefferi Ayalew
Published: January 2011

We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation–related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.
Cetuximab in Combination With Chemoradiotherapy Before Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma: A Prospective, Multicenter Phase IB/II Trial (SAKK 75/06)
Authors: Ruhstaller Thomas , Pless Miklos , Dietrich Daniel , Kranzbuehler Helmut , von Moos Roger , Moosmann Peter , Montemurro Michael , Schneider Paul M. , Rauch Daniel , Gautschi Oliver , Mingrone Walter , Widmer Lucas , Inauen Roman , Brauchli Peter , Hess Viviane
Published: January 2011

Purpose

This multicenter phase IB/II trial investigated cetuximab added to preoperative chemoradiotherapy for esophageal cancer.

Patients and Methods

Patients with resectable, locally advanced esophageal cancer received two 3-week cycles of induction chemoimmunotherapy (cisplatin 75 mg/m2 day 1, docetaxel 75 mg/m2 day 1, cetuximab 250 mg/m2 days 1, 8,15 [400 mg/m2 loading dose]) followed by chemoimmunoradiation therapy (CIRT) and surgery. CIRT consisted of 45 Gy radiotherapy (RT) plus concurrent cisplatin 25 mg/m2 and cetuximab 250 mg/m2 weekly for 5 weeks in cohort 1. If fewer than three of seven patients experienced limiting toxicity (LT), the next seven patients also received docetaxel (20 mg/m2 weekly × 5). If fewer than three patients experienced LTs, 13 additional patients were treated at this dose.

Results

In total, 28 patients (median age, 64 years) with predominantly node-positive (82%) esophageal adenocarcinoma (15 patients) or squamous cell carcinoma (13 patients) were enrolled and 24 (86%) completed the entire trimodal therapy. During CIRT, no LT occurred, rash was not exacerbated within the RT field, and the main grade 3 toxicities were esophagitis (seven patients), anorexia (three), fatigue (three), and thrombosis (two). Surgery (R0 resection) was performed in 25 patients. Anastomotic leakage occurred in three patients: two recovered spontaneously and one successfully underwent re-operation. There were no deaths at 30 days and no treatment-related mortality after 12 months. Nineteen patients (68%) showed complete or near complete pathologic regression.

Conclusion

Adding cetuximab to preoperative chemoradiotherapy is feasible without increasing postoperative mortality. Phase III investigation has begun based on the high histopathologic response and R0 resection rate.
Proofreading and spellchecking: A two-tier strategy for pre-mRNA splicing quality control
Authors: Egecioglu Defne E. , Chanfreau Guillaume
Published: January 2011

Multi-tier strategies exist in many biochemical processes to ensure a maximal fidelity of the reactions. In this review, we focus on the two-tier quality control strategy that ensures the quality of the products of the pre-mRNA splicing reactions catalyzed by the spliceosome. The first step in the quality control process relies on kinetic proofreading mechanisms that are internal to the spliceosome and that are performed by ATP-dependent RNA helicases. The second quality control step, spellchecking, involves recognition of unspliced pre-mRNAs or aberrantly spliced mRNAs that have escaped the first proofreading mechanisms, and subsequent degradation of these molecules by degradative enzymes in the nucleus or in the cytoplasm. This two-tier quality control strategy highlights a need for high fidelity and a requirement for degradative activities that eliminate defective molecules. The presence of multiple quality control activities during splicing underscores the importance of this process in the expression of genetic information.
Safety of Insulin Glargine Use in Pregnancy: A Systematic Review and Meta-Analysis
Authors: Pollex Erika , Moretti Myla E , Koren Gideon , Feig Denice S
Published: January 2011

Background

The prevalence of diabetes in women of childbearing age is increasing. As such, the number of pregnancies complicated by diabetes will inevitably increase. New insulin analogues such as the long-acting analogue Insulin glargine may represent beneficial treatment options in pregnancy by ensuring that patients achieve excellent glycemic control without risk of maternal hypoglycemia.

Objective

To determine the fetal safety of insulin glargine use in the treatment of diabetes in pregnancy compared with NPH insulin therapy.

Methods

A systematic review and meta-analysis was performed of all original human studies that reported neonatal outcomes among women with pregestational or gestational diabetes who were managed with either insulin glargine or NPH insulin during pregnancy. A systematic literature search was conducted using MEDLINE, EMBASE, CINAHL, the Cochrane Central Register for Controlled Trials database, and Web of Science from 1980 to June 1, 2010. Outcomes included large size for gestational age, macrosomia, neonatal hypoglycemia, neonatal intensive care unit admissions, birth trauma, congenital anomalies, preterm delivery, perinatal mortality, respiratory distress, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were computed with 95% confidence intervals.

Results:

Eight studies reporting on a total of 702 women with pregestational or gestational diabetes in pregnancy treated with either insulin glargine (n = 331) or NPH insulin (n = 371) met the inclusion criteria. There were no statistically significant differences in the occurrence of fetal outcomes studied with the use of insulin glargine compared to NPH insulin.

Conclusions:

No evidence has been documented for increased adverse fetal outcomes with the use of insulin glargine in pregnancy compared to the use of NPH insulin. These results increase the choices for women requiring basal insulin therapy in pregnancy.
Effectiveness of Pharmacist Care in the Improvement of Adherence to Antidepressants: A Systematic Review and Meta-Analysis
Authors: Rubio-Valera Maria , Serrano-Blanco Antoni , Magdalena-Belío Jesús , Fernández Ana , García-Campayo Javier , March Pujol Marian , López del Hoyo Yolanda
Published: January 2011

Background

Pharmacists can play a decisive role in the management of ambulatory patients with depression who have poor adherence to antidepressant drugs.

Objective

To systematically evaluate the effectiveness of pharmacist care in improving adherence of depressed outpatients to antidepressants.

Methods

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. RCTs were identified through electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, Institute for Scientific Information Web of Knowledge, and Spanish National Research Council) from inception to April 2010, reference lists were checked, and experts were consulted. RCTs that evaluated the impact of pharmacist interventions on improving adherence to antidepressants in depressed patients in an outpatient setting (community pharmacy or pharmacy service) were included, Methodologic quality was assessed and methodologic details and outcomes were extracted in duplicate.

Results:

Six RCTs were identified. A total of 887 patients with an established diagnosis of depression who were initiating or maintaining pharmacologic treatment with antidepressant drugs and who received pharmacist care (459 patients) or usual care (428 patients) were included in the review. The most commonly reported interventions were patient education and monitoring, monitoring and management of toxicity and adverse effects, adherence promotion, provision of written or visual information, and recommendation or implementation of changes or adjustments in medication. Overall, no statistical heterogeneity or publication bias was detected. The pooled odds ratio, using a random effects model, was 1.64 (95% CI 1.24 to 2.17). Subgroup analysis showed no statistically significant differences in results by type of pharmacist involved, adherence measure, diagnostic tool, or analysis strategy.

Conclusions:

These results suggest that pharmacist intervention is effective in the improvement of patient adherence to antidepressants. However, data are still limited and we would recommend more research in this area, specifically outside of the US.
Dopamine D3Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice
Authors: Dowling Pascal , Klinker Florian , Stadelmann Christine , Hasan Kenan , Paulus Walter , Liebetanz David
Published: January 2011

Restless legs syndrome (RLS) is a common neurological disorder whose exact pathophysiological mechanism remains unclear despite the successful use of dopaminergic treatment and recent discovery of predisposing genetic factors. As iron deficiency has been associated with RLS for some patients and there is evidence for decreased spinal dopamine D3-receptor (D3R) signaling in RLS, we aimed at establishing whether D3R activity and iron deficiency share common pathways within the pathophysiology of RLS sensory and motor symptoms.

Using a combined mouse model of iron deficiency and dopamine D3-receptor deficiency (D3R−/−), circadian motor symptoms were evaluated by continuous recording of spontaneous wheel running activity. Testing the acute and persistent pain responses with the hot-plate test and formalin test, respectively, assessed sensory symptoms.

A 15 week iron-deficient (ID) diet alone increased acute and persistent pain responses as compared to control diet. As compared to C57BL/6 (WT), homozygous D3R−/− mice already exhibited elevated responses to acute and persistent pain stimuli, where the latter was further elevated by concurrent iron deficiency. ID changed the circadian activity pattern toward an increased running wheel usage before the resting period, which resembled the RLS symptom of restlessness before sleep. Interestingly, D3R−/− shifted this effect of iron deficiency to a time point 3–4 h earlier.

The results confirm the ability of iron deficiency and D3R−/− to evoke sensory and motor symptoms in mice resembling those observed in RLS patients. Furthermore this study suggests an increase of ID-related sensory symptoms and modification of ID-related motor symptoms by D3R−/−.
Heat Shock Cognate Protein 70 Regulates Gephyrin Clustering
Authors: Machado Patricia , Rostaing Philippe , Guigonis Jean-Marie , Renner Marianne , Dumoulin Andréa , Samson Michel , Vannier Christian , Triller Antoine
Published: January 2011

Formation and stabilization of postsynaptic glycine receptor (GlyR) clusters result from their association with the polymerized scaffold protein gephyrin. At the cell surface, lateral diffusion and local trapping of GlyR by synaptic gephyrin clusters is one of the main factors controlling their number. However, the mechanisms regulating gephyrin/GlyR cluster sizes are not fully understood. To identify molecular binding partners able to control gephyrin cluster stability, we performed pull-down assays with full-length or truncated gephyrin forms incubated in a rat spinal cord extract, combined with mass spectrometric analysis. We found that heat shock cognate protein 70 (Hsc70), a constitutive member of the heat shock protein 70 (Hsp70) family, selectively binds to the gephyrin G-domain. Immunoelectron microscopy of mouse spinal cord sections showed that Hsc70 could be colocalized with gephyrin at inhibitory synapses. Furthermore, ternary Hsc70-gephyrin-GlyR coclusters were formed following transfection of COS-7 cells. Upon overexpression of Hsc70 in mouse spinal cord neurons, synaptic accumulation of gephyrin was significantly decreased, but GlyR amounts were unaffected. In the same way, Hsc70 inhibition increased gephyrin accumulation at inhibitory synapses without modifying GlyR clustering. Single particle tracking experiments revealed that the increase of gephyrin molecules reduced GlyR diffusion rates without altering GlyR residency at synapses. Our findings demonstrate that Hsc70 regulates gephyrin polymerization independently of its interaction with GlyR. Therefore, gephyrin polymerization and synaptic clustering of GlyR are uncoupled events.
Choice from Non-Choice: Predicting Consumer Preferences from Blood Oxygenation Level-Dependent Signals Obtained during Passive Viewing
Authors: Levy Ifat , Lazzaro Stephanie C. , Rutledge Robb B. , Glimcher Paul W.
Published: January 2011

Decision-making is often viewed as a two-stage process, where subjective values are first assigned to each option and then the option of the highest value is selected. Converging evidence suggests that these subjective values are represented in the striatum and medial prefrontal cortex (MPFC). A separate line of evidence suggests that activation in the same areas represents the values of rewards even when choice is not required, as in classical conditioning tasks. However, it is unclear whether the same neural mechanism is engaged in both cases. To address this question we measured brain activation with functional magnetic resonance imaging while human subjects passively viewed individual consumer goods. We then sampled activation from predefined regions of interest and used it to predict subsequent choices between the same items made outside of the scanner. Our results show that activation in the striatum and MPFC in the absence of choice predicts subsequent choices, suggesting that these brain areas represent value in a similar manner whether or not choice is required.
Role of Prefrontal Cortex in Conscious Visual Perception
Authors: Libedinsky Camilo , Livingstone Margaret
Published: January 2011

Early visual areas are required for conscious visual perception, but recent evidence suggests that parts of the frontal lobe might also play a key role. However, it remains unclear whether frontal brain areas are involved in visual perception or merely use information from visual regions to drive behavior. One such frontal cortical area, the frontal-eye field (FEF), has been shown to have fast visual responses, thought to reflect mostly low-level visual processing, and delayed responses that correlate with perceptual reports. The latter observation is consistent with the idea that FEF uses visual information from (slower) visual regions to guide behavior. Here we ask whether fast visual responses in FEF also carry information related to the perceptual state of animals. We recorded single-cell activity in two monkeys trained to report the presence or absence of a visual target under conditions that evoke the illusory disappearance of the target (motion-induced blindness). We found that fast responses in FEF strongly correlated with the perceptual report of the animal. It is unlikely that short-latency perceptually correlated activity is inherited from early visual areas, since response latencies in FEF are shorter than those of visual areas with perceptually correlated activity. These results suggest that frontal brain areas are involved in generating the contents of visual perception.
Phosphoinositide 3-Kinase-Dependent Antagonism in Mammalian Olfactory Receptor Neurons
Authors: Ukhanov Kirill , Brunert Daniela , Corey Elizabeth A. , Ache Barry W.
Published: January 2011

Phosphoinositide signaling, in particular, phosphoinositide 3-kinase (PI3K) signaling, has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs). To better understand this phenomenon we investigated PI3K-dependent inhibition between single odorant pairs. The concentration-dependent inhibition of the response of native rat ORNs to octanol by citral is PI3K dependent; blocking PI3K activity with the β and γ isoform-specific inhibitors AS252424 (5-[5-(4-fluoro-2-hydroxy-phenyl)-furan-2-ylmethylene]-thiazolidine-2,4-dione) and TGX221(7-methyl-2-(4-morpholinyl)-9-[1-(phenylamino)ethyl]-4H-pyrido [1,2-a]pyrimidin-4-one) eliminated or strongly reduced the inhibition. Interestingly, blocking PI3K also changed the apparent agonist strength of the otherwise noncompetitive antagonist citral. The excitation evoked by citral after blocking PI3K, could be suppressed by the adenylate cyclase III (ACIII) blockers MDL12330A (cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride) and SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine], indicating that citral could also activate ACIII, presumably through the canonical olfactory receptor (OR). The G-protein Gβγ subunit blockers suramin (8,8′-[carbonylbis[imino-3,1-phenylen ecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bis-1,3,5-naphthalenetrisulfonic acid), gallein (3′,4′,5′,6′-tetrahydroxyspiro[isobenzofuran-1(3H),9'-(9H)xanthen]-3-one), and M119 (cyclohexanecarboxylic acid [2-(4,5,6-trihydroxy-3-oxo-3H-xanthen-9-yl)-(9CI)]) suppressed citral's inhibition of the response to octanol, indicating that the activation of PI3K by citral was G-protein dependent, consistent with the idea that inhibition acts via the canonical OR. Lilial similarly antagonized the response to isoamyl acetate in other ORNs, indicating the effect generalizes to at least one other odorant pair. The ability of methyl-isoeugenol, limonene, α-pinene, isovaleric acid, and isosafrole to inhibit the response of other ORNs to IBMX (3-isobutyl-1-methylxanthine)/forskolin in a PI3K-dependent manner argues the effect generalizes to yet other structurally dissimilar odorants. Our findings collectively raise the interesting possibility that the OR serves as a molecular logic gate when mammalian ORNs are activated by natural, complex mixtures containing both excitatory and inhibitory odorants.
Central Amygdala Activity during Fear Conditioning
Authors: Duvarci Sevil , Popa Daniela , Paré Denis
Published: January 2011

The central amygdala (Ce), particularly its medial sector (CeM), is the main output station of the amygdala for conditioned fear responses. However, there is uncertainty regarding the nature of CeM control over conditioned fear. The present study aimed to clarify this question using unit recordings in rats. Fear conditioning caused most CeM neurons to increase their conditioned stimulus (CS) responsiveness. The next day, CeM cells responded similarly during the recall test, but these responses disappeared as extinction of conditioned fear progressed. In contrast, the CS elicited no significant average change in central lateral (CeL) firing rates during fear conditioning and a small but significant reduction during the recall test. Yet, cell-by-cell analyses disclosed large but heterogeneous CS-evoked responses in CeL. By the end of fear conditioning, roughly equal proportions of CeL cells exhibited excitatory (CeL+) or inhibitory (CeL−) CS-evoked responses (∼10%). The next day, the proportion of CeL−cells tripled with no change in the incidence of CeL+cells, suggesting that conditioning leads to overnight synaptic plasticity in an inhibitory input to CeL−cells. As in CeM, extinction training caused the disappearance of CS-evoked activity in CeL. Overall, these findings suggest that conditioned freezing depends on increased CeM responses to the CS. The large increase in the incidence of CeL−but not CeL+cells from conditioning to recall leads us to propose a model of fear conditioning involving the potentiation of an extrinsic inhibitory input (from the amygdala or elsewhere) to CeL, ultimately leading to disinhibition of CeM neurons.
Pädagogische Potentiale von Kontaktzonen. Paradoxien und Irritationen einer schulischen Begegnung
Authors: Ferrin Nino , Blaschke Gerald
Published: January 2011

In this research project the concept of the contact zone is being extended to the field of school encounters, where the subjects in interactions are confronted with the other. Here, the contact zone is not restricted to be of colonial relatedness but focuses the power relations when dealing with one′s own and other′s types of perception and action. The clash with unfamiliar cultural influences can be categorized as a contact zone, if the situation is characterized by an uncommon or extraordinary interaction form. Thus the subjects are not entirely foreign to each other. Still the metaphor of the contact zone might be productive for the empirical field of interpreting practices in which pedagogical differences or confronting orientations emerge rather performatively in a way not planned didactically.
Beyond Ritual as Performance. Towards Ritual as Dynamics and Virtuality
Authors: Kapferer Bruce
Published: January 2011

The essay addresses Victor Turner′s radical approach to the study of ritual and in particular the creative and generative potential of liminal processes. Two objectives guide the analysis. The first is to develop an approach that is not over-constrained by the dramatic or theatrical metaphor of performance that dominates much discussion of ritual. The second is to reorient an approach to the liminal as a stage in a process in itself and to explore it in terms of the concept of the virtual. In other words, the liminal as thoroughly an opening of potential and innovative emergence, a major direction of Turner′s approach.
Schreiben, um übersetzt zu werden? Tschechische Literatur zwischen Originalität und ‚euroromán‘
Authors: Hultsch Anne
Published: January 2011

The alleged crisis of Czech literature is currently a widely discussed topic among Czech writers. Therefore I analyse writing strategies that are used to overcome small context in this paper. Thereby the question of translatability plays an important part. Three approaches are followed: 1) to force originality, 2) to write ‚Euro-novels‘, 3) to change writing language. The overall picture is heterogeneous. We can consider this heterogeneity as a chance for Czech literature.
Buchbesprechung
Authors: Bruns Thomas
Published: January 2011

Belentschikow, Renate (Hrsg.), Russisch-Deutsches Wörterbuch (RDW). Im Auftrag der Akademie der Wissenschaften und der Literatur, Mainz. Wiesbaden: Harrassowitz Verlag, 2003ff.
A reduction method of dynamic false contour utilizing the frame‐rate‐control method with suppression of the side effect on PDPs
Authors: Ohara Takatoshi , Akiyama Yasuhiro , Nagata Koji , Nitta Hiroyuki , Kudo Yasuyuki
Published: January 2011

Abstract—The plasma‐display panel (PDP) is a type of flat‐panel display that can display a high‐quality image. However, when moving images are displayed, annoying disturbances such as false contour noise occurs. This noise is called dynamic false contour (DFC). To achieve a higher‐quality image, DFC has to be reduced. Therefore, a new method to reduce DFC is proposed. To find a way to reduce DFC, a new evaluation value for it has been defined: the evaluation value of dynamic false contour (EVDFC). This value is defined on the basis of a person's subjective evaluation. By applying this value, the cause that generates DFC can be identified. On the basis of these studies, a new method for reducing DFC by applying frame‐rate control (FRC) with suppression of the side effect is proposed. This improved method can be used to provide high‐quality images.
Amorphous‐oxide TFT backplane for large‐sized AMOLED TVs
Authors: Mo Yeon Gon , Kim Minkyu , Kang Chul Kyu , Jeong Jong Han , Park Yong Sung , Choi Chaun Gi , Kim Hye Dong , Kim Sang Soo
Published: January 2011

Abstract— Amorphous‐oxide thin‐film‐transistor (TFT) arrays have been developed as TFT backplanes for large‐sized active‐matrix organic light‐emitting‐diode (AMOLED) displays. An amorphous‐IGZO (indium gallium zinc oxide) bottom‐gate TFT with an etch‐stop layer (ESL) delivered excel lent electrical performance with a field‐effect mobility of 21 cm2/V‐sec, an on/off ratio of >108, and a subthreshold slope (SS) of 0.29 V/dec. Also, a new pixel circuit for AMOLED displays based on amorphous‐oxide semiconductor TFTs is proposed. The circuit consists of four switching TFTs and one driving TFT. The circuit simulation results showed that the new pixel circuit has better performance than conventional threshold‐voltage (VTH) compensation pixel circuits, especially in the negative state. A full‐color 19‐in. AMOLED display with the new pixel circuit was fabricated, and the pixel circuit operation was verified in a 19‐in. AMOLED display. The AMOLED display with a‐IGZO TFT array is promising for large‐sized TV because a‐IGZO TFTs can provide a large‐sized backplane with excellent uniformity and device reliability.
Screening and Evaluation of Polyhydroxybutyrate-Producing Strains from Indigenous Isolate Cupriavidus taiwanensis Strains
Authors: Wei Yu-Hong , Chen Wei-Chuan , Huang Chin-Kuei , Wu Ho-Shing , Sun Yi-Ming , Lo Chi-Wei , Janarthanan Om-Murugan
Published: January 2011

Polyhydroxyalkanoate (PHA) is a biodegradable material with many potential biomedical applications, including medical implants and drug delivery. This study developed a system for screening production strains in order to optimize PHA production in Cupriavidus taiwanensis 184, 185, 186, 187, 204, 208, 209 and Pseudomona oleovorans ATCC 29347. In this study, Sudan black B staining, Infrared (IR) and Gas Chromatography (GC) analysis indicated that the best strain for PHA synthesis is C. taiwanensis 184, which obtains polyhydroxybutyrate (PHB). Cultivation of C. taiwanensis 184 under a pH of 7.0, at 30 °C, and at an agitation rate of 200 rpm, obtained a PHB content of 10% and PHB production of 0.14 g/L. The carbon and nitrogen types selected for analysis of PHB production by C. taiwanensis 184 were gluconic acid and NH4Cl, respectively. Optimal carbon/nitrogen ratio for PHB production was also determined. This study demonstrated a PHB content of 58.81% and a PHB production of 2.44 g/L when the carbon/nitrogen ratio of 8/1 was selected for C. taiwanensis 184. A two‑stage fermentation strategy significantly enhanced PHB content and PHB production. Under a two-stage fermentation strategy with nutrient‑limited conditions, C. taiwanensis 184 obtained a PHB content of 72% and a PHB concentration of 7 g/L. Finally, experimental results confirmed that optimizing the growth medium and fermentation conditions for cultivating the indigenous C. taiwanensis 184 strain substantially elevated PHB content from 10% to 72% and PHB production from 0.14 g/L to 7 g/L, respectively.
Gelatin Functionalization of Biomaterial Surfaces: Strategies for Immobilization and Visualization
Authors: Van Vlierberghe Sandra , Vanderleyden Els , Boterberg Veerle , Dubruel Peter
Published: January 2011

In the present work, the immobilization of gelatin as biopolymer on two types of implantable biomaterials, polyimide and titanium, was compared. Both materials are known for their biocompatibility while lacking cell-interactive behavior. For both materials, a pre-functionalization step was required to enable gelatin immobilization. For the polyimide foils, a reactive succinimidyl ester was introduced first on the surface, followed by covalent grafting of gelatin. For the titanium material, methacrylate groups were first introduced on the Ti surface through a silanization reaction. The applied functionalities enabled the subsequent immobilization of methacrylamide modified gelatin. Both surface modified materials were characterized in depth using atomic force microscopy, static contact angle measurements, confocal fluorescence microscopy, attenuated total reflection infrared spectroscopy and X-ray photo-electron spectroscopy. The results indicated that the strategies elaborated for both material classes are suitable to apply stable gelatin coatings. Interestingly, depending on the material class studied, not all surface analysis techniques are applicable.
Electrospraying, a Reproducible Method for Production of Polymeric Microspheres for Biomedical Applications
Authors: Bock Nathalie , Woodruff Maria A. , Hutmacher Dietmar W. , Dargaville Tim R.
Published: January 2011

The ability to reproducibly load bioactive molecules into polymeric microspheres is a challenge. Traditional microsphere fabrication methods typically provide inhomogeneous release profiles and suffer from lack of batch to batch reproducibility, hindering their potential to up-scale and their translation to the clinic. This deficit in homogeneity is in part attributed to broad size distributions and variability in the morphology of particles. It is thus desirable to control morphology and size of non-loaded particles in the first instance, in preparation for obtaining desired release profiles of loaded particles in the later stage. This is achieved by identifying the key parameters involved in particle production and understanding how adapting these parameters affects the final characteristics of particles. In this study, electrospraying was presented as a promising technique for generating reproducible particles made of polycaprolactone, a biodegradable, FDA-approved polymer. Narrow size distributions were obtained by the control of electrospraying flow rate and polymer concentration, with average particle sizes ranging from 10 to 20 µm. Particles were shown to be spherical with a homogeneous embossed texture, determined by the polymer entanglement regime taking place during electrospraying. No toxic residue was detected by this process based on preliminary cell work using DNA quantification assays, validating this method as suitable for further loading of bioactive components.
A Polyvinyl Alcohol-Polyaniline Based Electro-Conductive Hydrogel for Controlled Stimuli-Actuable Release of Indomethacin
Authors: Tsai Tong-Sheng , Pillay Viness , Choonara Yahya E. , Du Toit Lisa C. , Modi Girish , Naidoo Dinesh , Kumar Pradeep
Published: January 2011

Electro-conductive hydrogels based on poly(vinyl alcohol), crosslinked with diethyl acetamidomalonate as the hydrogel component, were engineered using polyaniline as the inherently conductive component, and fabricated in the form of cylindrical devices to confer electro-actuable release of the model drug indomethacin. The hydrogels were characterized for their physicochemical and physicomechanical properties. Cyclic voltammetry was employed for electro-activity and conductivity analysis. Drug entrapment efficiency ranged from 65–70%. “ON-OFF” switchable drug release was obtained by periodically applying-removing-reapplying an electric potential ranging from 0.3–5.0 V for 60 seconds at hourly intervals and the cumulative drug release obtained ranged from 4.7–25.2% after four release cycles respectively. The electro-stimulated release of indomethacin was associated with the degree of crosslinking, the polymeric ratio and drug content. A Box-Behnken experimental design was constructed employing 1.2 V as the baseline potential difference. The devices demonstrated superior swellability and high diffusivity of indomethacin, in addition to high electrical conductivity with “ON-OFF” drug release kinetics via electrical switching. In order to investigate the electro-actuable release of indomethacin, molecular mechanics simulations using AMBER-force field were performed on systems containing water molecules and the poly(vinyl alcohol)-polyaniline composite under the influence of an external electric field. Various interaction energies were monitored to visualize the effect of the external electric field on the erosion of polyaniline from the co-polymeric matrix. This strategy allows the electro-conductive hydrogels to be suitably applied for controlled, local and electro-actuable drug release while sustaining a mild operating environment.
Retraction: Najafabadi, A.T. Study of Soil Scattering Coefficients in Combination with Diesel for a Slightly Rough Surface in the Cj Band. Remote Sens. 2010, 2, 115-123.
Authors: Lin Shu-Kun
Published: January 2011

It has been brought to our attention by a reader of Remote Sensing that substantial portions of this article [1] have been copied verbatim from an earlier published thesis without credit. After confirming this plagiarism with the authors, we have determined that indeed this manuscript clearly violates our policy on originality of all material submitted for publication and the generally accepted ethics of scientific publication. Consequently, the Editorial Team and Publisher have determined that it should be retracted. We apologize for any inconvenience this may cause.
SS-MIX: A Ministry Project to Promote Standardized Healthcare Information Exchange
Authors: Kimura M. , Nakayasu K. , Ohshima Y. , Fujita N. , Nakashima N. , Jozaki H. , Numano T. , Shimizu T. , Shimomura M. , Sasaki F. , Fujiki T. , Nakashima T. , Toyoda K. , Hoshi H. , Sakusabe T. , Naito Y. , Kawaguchi K. , Watanabe H. , Tani S.
Published: January 2011

Objectives: To promote healthcare information exchange between providers and to allow hospital information systems (HIS) export information in standardized format (HL7 and DICOM) in an environment of widespread legacy systems, which only can export data in proprietary format.

Methods: Through the Shizuoka prefecture EMR project in 2004–2005, followed by the ministry’s SS-MIX project, many software products have been provided, which consist of 1) a standardized storage to receive HL7 v2.5 mes sages of patient demographics, prescription orders, laboratory results, and diagnostic disease in ICD-10, 2) a referral letter creation system, 3) a formatted document creation system, 4) a progress note/nursing record system, and 5) an archive/viewer to incorporate incoming healthcare data CD and allow users to view on HIS terminal. Meanwhile, other useful applications have been produced, such as adverse event reporting and clinical information retrieval. To achieve the above-mentioned objectives, these software products were created and propagated, because users can use these software products, provided that their HIS can export the above information to the standardized storage in HL7 v2.5 format.

Results: In 20 hospitals of Japan, the standardized storage has been installed and some applications have been used. As major HIS vendors are shipping HIS with HL7 export function since 2007, HIS of 594 hospitals in Japan became capable of exporting data in HL7 v2.5 format (as of March 2010).

Conclusions: In high CPOE installation rate (85% in 400+ bed hospitals), though most of them only capable of exporting data in proprietary format, prefecture and ministry projects were effective to promote healthcare information exchange between providers. The standardized storage became an infrastructure for many useful applications, and many hospitals started using them. Ministry designation of proposed healthcare standards was effective so as to allow vendors to conform their products, and users to install them.
Comparison of Multiplex Restriction Fragment Mass Polymorphism and Sequencing Analyses for Detecting Entecavir Resistance in Chronic Hepatitis B
Authors: Han Kyung Ho , Hong Sun Pyo , Choi Seo Hee , Shin Soo-Kyung , Cho Sung Won , Ahn Sang Hoon , Hahn Ji-Sook , Kim Soo-Ok
Published: January 2011

Background

Drug resistance is a major limitation to the long-term efficacy of controlling chronic hepatitis B (CHB). There is a growing need to analyse multiple mutations associated with drug resistance because sequential or combinational use of antivirals is increasingly being used in treatment. In this study, we introduced a multiplex restriction fragment mass polymorphism (RFMP) assay for detecting mutations conferring entecavir and lamivudine resistance, and compared its performance with direct or clonal sequencing assays.

Methods

Multiplex PCR was performed with mixed primers designed to interrogate rt184, rt202, rt204 and rt250. The PCR products were digested with restriction enzymes and the resulting fragments were analysed by mass spectrometry. A total of 251 serum samples, taken serially from 45 patients who received entecavir treatment after confirmed diagnosis of lamivudine resistance and inadequate adefovir dipivoxil response, were analysed by the multiplex RFMP assay.

Results

The multiplex RFMP assay correctly identified known viral sequences with sufficient analytical sensitivity to detect as few as 100 IU/ml of HBV and with superior ability to determine haplotypes composed of neighbouring variations. Complex mutational patterns and relative abundances determined by multiplex RFMP assay were in good concordance with results obtained by direct or clonal sequencing analyses. Defined mixtures were successfully and consistently identified at 2% relative concentration of mutant versus wild-type virus by the assay.

Conclusions

The multiplex RFMP assay is an accurate and sensitive means to detect entecavir and lamivudine resistance mutations, simultaneously. The method is expected to enable early and efficient diagnosis of multiple drug resistance mutations for optimal management of CHB.