bluuebunny/crossref_metadata_2025 huggingface dataset:
TWIST1 Is an ERK1/2 Effector That Promotes Invasion and Regulates MMP-1 Expression in Human Melanoma Cells
Authors: Weiss Michele B. , Abel Ethan V. , Mayberry Melanie M. , Basile Kevin J. , Berger Adam C. , Aplin Andrew E.
Published: December 2012

Tumor cells often use developmental processes to progress toward advanced disease. The E-box transcription factor TWIST1 is essential to epithelial–mesenchymal transition (EMT) and cell migration in the developing neural crest. In melanoma, which derives from the neural crest cell lineage, enhanced TWIST1 expression has been linked to worse clinical prognosis. However, mechanisms underlying TWIST1 expression and whether aberrant TWIST1 levels promote steps in melanoma progression remain unknown. Here, we report that elevated TWIST1 mRNA/protein expression is dependent on extracellular signal-regulated kinase (ERK)1/2 signaling, which is hyperactive in the majority of melanomas. We show that TWIST1 protein levels are especially high in melanoma cell lines generated from invasive, premetastatic stage tumors. Furthermore, TWIST1 expression is required and sufficient to promote invasion through Matrigel and spheroid outgrowth in three-dimensional dermal-mimetic conditions. Alterations to spheroid outgrowth were not as a result of altered cell death, cell-cycle profile, or paradigm EMT protein changes. Importantly, we identify matrix metalloproteinase-1 (MMP-1) as a novel downstream target of TWIST1. We have determined that TWIST1 acts, in a dose-dependent manner, as a mediator between hyperactive ERK1/2 signaling and regulation of MMP-1 transcription. Together, these studies mechanistically show a previously unrecognized interplay between ERK1/2, TWIST1, and MMP-1 that is likely significant in the progression of melanoma toward metastasis. Cancer Res; 72(24); 6382–92. ©2012 AACR.
Transesophageal Bronchoscopic Ultrasound-Guided Fine Needle Aspiration for Diagnosis of Sarcoidosis
Authors: Oki Masahide , Saka Hideo , Kitagawa Chiyoe , Kogure Yoshihito , Murata Naohiko , Adachi Takashi , Ichihara Shu , Moritani Suzuko
Published: December 2012

Background: Several studies have reported that specimens from mediastinal lesions located adjacent to the esophagus can be sampled using an ultrasound bronchoscope instead of an ultrasound endoscope. Objectives: The aim of this study was to evaluate the diagnostic utility of transesophageal bronchoscopic ultrasound-guided fine needle aspiration using an ultrasound bronchoscope in patients with stage I/II sarcoidosis. Methods: Thirty-three patients suspected of having stage I/II sarcoidosis were included in this prospective study. Needle aspiration through the esophagus using an ultrasound bronchoscope was performed for hilar and/or mediastinal lymph nodes. The final diagnosis of sarcoidosis was based on clinicoradiological compatibility and pathological findings. Results: A total of 62 lymph nodes with a mean shortest diameter of 13.6 mm were examined. Of the 33 patients enrolled, 29 were given a final diagnosis of sarcoidosis. Four of the residual patients had other diseases (1 lung cancer, 1 tuberculosis, 2 non-specific lymphadenitis). Transesophageal bronchoscopic ultrasound-guided fine needle aspiration showed noncaseating epithelioid cell granulomas in 25 of 29 patients (86%; 95% confidence interval 73–100) with the final diagnosis of sarcoidosis. No complications were observed. Conclusions: Transesophageal bronchoscopic ultrasound-guided fine needle aspiration is feasible, safe and accurate for the diagnosis of stage I/II sarcoidosis.
Inflammatory Markers and Clustered Cardiovascular Disease Risk Factors in Danish Adolescents
Authors: Bugge Anna , El-Naaman Bianca , McMurray Robert G. , Froberg Karsten , Nielsen Claus Henrik , Müller Klaus , Andersen Lars Bo
Published: December 2012

Aims: To evaluate the associations between inflammatory markers and clustering of cardiovascular disease (CVD) risk factors, and to examine how inflammatory markers and CVD risk are related to fatness and cardiorespiratory fitness (VO2peak) in adolescents. Methods: Body mass and height, skinfolds and blood pressure of 413 adolescents (mean age 13.4 ± 0.3 years) were measured. Circulating fasting levels of glucose, insulin, lipids, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)α, soluble TNF receptor-1 (sTNFR1), interleukin (IL)-6 and IL-1 receptor antagonist (IL-1Ra) were measured. VO2peak was measured in progressive tests to exhaustion. CVD risk was expressed as a clustered z-score, summing standardized values of individual risk factors. Results: The clustered z-score was negatively associated with adiponectin and positively associated with CRP, IL-6 and TNFα (all p values <0.05). The associations with adiponectin, CRP and IL-6 were stronger for the fattest adolescents. VO2peak was negatively correlated with clustered z-score, adiponectin and IL-6 and positively related to systolic blood pressure. The sum of four skinfolds was inversely related to adiponectin and positively correlated to body mass index, systolic blood pressure, homeostasis model assessment, clustered z-score and CRP. Conclusion: In adolescents, CVD risk was associated with alternations in adiponectin, TNFα, CRP and IL-6, and related to both VO2peak and fatness.
Infiltration of Natural Caries Lesions in Relation to Their Activity Status and Acid Pretreatment in vitro
Authors: Neuhaus K.W. , Schlafer S. , Lussi A. , Nyvad B.
Published: December 2012

This study aimed at testing how active and inactive enamel caries lesions differ by their degree of resin infiltration, and whether the choice of acid pretreatment plays a crucial role. Four examiners assessed 104 human molars and premolars with noncavitated enamel lesions and classified them as ‘active’ or ‘inactive’ using the Nyvad criteria. Forty-five teeth were included in this study after independent unanimous lesion activity assessment. Lesions were cut perpendicularly into 2 halves. Each half lesion was pretreated with either 15% hydrochloric acid or 35% phosphoric acid. The lesions were infiltrated after staining with rhodamine isothiocyanate. Thin sections of 100 µm were prepared and the specimens were bleached with 30% hydrogen peroxide. The specimens were then counterstained with sodium fluorescein, subjected to confocal laser scanning microscopy and analyzed quantitatively. Outcome parameters were maximum and average infiltration depths as well as relative penetration depths and areas. In active lesions no significant difference of percentage maximum penetration depth and percentage average penetration depth between lesions pretreated with hydrochloric or phosphoric acid could be observed. In inactive lesions, however, phosphoric acid pretreatment resulted in significantly lower penetration compared to hydrochloric acid pretreatment. Surface conditioning with hydrochloric acid led to similar infiltration results in active and inactive lesions. Moreover, inactive lesions showed greater variability in all assessed infiltration parameters than did active lesions. In conclusion, caries lesion activity and acid pretreatment both influenced the infiltration. The use of phosphoric acid to increase permeability of the surface layer of active lesions should be further explored.
Platelet genetic biomarker quantification: Comparison of fluorescent microspheres and PCR platforms
Authors: Huang Erya , Zhu Wei , Dhundale Anil , Bahou Wadie , Gnatenko Dmitri
Published: December 2012

The platelet transcriptome has been extensively characterised using distinct genetic profiling platforms, with evolving evidence for differential expression patterns between healthy individuals and subject cohorts with various haematologic and cardiovascular disorders. Traditional technological platforms for platelet genetic biomarker quantification have limited applicability for clinical molecular diagnostics due to inherent complexities related to RNA isolation and analysis. We have previously established the feasibility of fluorescent microspheres as a simple and reproducible strategy for simultaneous quantification of platelet mRNAs from small volume of blood using intact platelets. We now extend these observations by formally comparing in a 50-member normal cohort the cross-platform behaviour of fluorescent microspheres to the currently accepted Q-PCR standard, using a clinically relevant 15-biomarker gene subset able to discriminate among normal and thrombocytosis cohorts. When compared to Q-PCR, genetic biomarker quantification using fluorescent microspheres demonstrated lower coefficients of variation for low-abundant transcripts, better linearity in serially diluted samples, and good overall between-platform consistency via the geometric mean regression. Neither platform demonstrated age or gender effects for any of the 15 biomarkers studied. Binding site saturation for highly abundant transcripts using fluorescent microspheres can be readily eliminated using an optimal platelet number corresponding to 0.3 ml of peripheral blood, additionally applicable to thrombocytopenic cohorts. These data provide a detailed cross-platform analysis using a relevant biomarker subset, further highlighting the applicability of fluorescent microspheres as potentially superior to Q-PCR for platelet mRNA diagnostics.
An engineered fibrinogen variant AαQ328,366P does not polymerise normally, but retains the ability to form α cross-links
Authors: Ping Lifang , Song Jaewoo , Seo Joo-Young , Choi Tae-Youn , Choi Jong-Rak , Gorkun Oleg , Lord Susan , Park Rojin
Published: December 2012

A fibrin clot is stabilised through the formation of factor XIIIa-catalysed intermolecular ε -lysyl-γ -glutamyl covalent cross-links between α chains to form α polymers and between γ chains to form γ dimers. In a previous study we characterised fibrinogen Seoul II, a heterozygous dysfibrinogen in which a cross-linking acceptor site in Aα chain, Gln328, was replaced with Pro (AαQ328P). Following on the previous study, we investigated whether the alteration of Gln residues Aα328 and Aα366 affects fibrin polymerisation and α chain cross-linking. We have expressed three recombinant fibrinogens: AαQ328P, AαQ366P, and AαQ328,366P in Chinese hamster ovary cells, purified these fibrinogens from the culture media and performed biochemical tests to see how the introduced changes affect fibrin polymerisation and α chain cross-linking. Thrombin-catalysed fibrin polymerisation of all variants was impaired with the double mutation being the most impaired. In contrast, sodium dodecyl sulfate–polyacrylamide gel electrophoresis and immunoblot analysis showed α polymer formation with all three engineered proteins. This study demonstrates that AαQ328 and AαQ366 are important for normal fibrin clot formation and in the absence of residues AαQ328 and AαQ366, other Gln residues in the a chain can support FXIIIa-catalysed fibrin cross-linking.
Connexin45 Regulates Endothelial-Induced Mesenchymal Cell Differentiation Toward a Mural Cell Phenotype
Authors: Fang Jennifer S. , Dai Cuiping , Kurjiaka David T. , Burt Janis M. , Hirschi Karen K.
Published: December 2012

Objective—

The focus of this study was to investigate the role of connexin (Cx) 45 in endothelial-induced mural cell differentiation.

Methods and Results—

We created mural cell precursors that stably express only Cx45 in Cx43-deficient mesenchymal cells (ReCx45), and used our in vitro model of blood vessel assembly to assess the capacity of this Cx to support endothelial-induced mural cell differentiation. Lucifer Yellow dye injection and dual whole-cell patch clamping revealed that functional gap junctions exhibiting properties of Cx45-containing channels formed among ReCx45 transfectants, and between ReCx45 and endothelial cells. Heterocellular Cx45-containing gap junction channels enabled transforming growth factor-β activation and promoted the upregulation of mural cell–specific proteins in the mesenchymal precursors.

Conclusion—

These studies reveal a critical role for Cx45 in the regulation of endothelial-induced mural cell differentiation, which is consistent with the phenotype of Cx45-deficient embryos that exhibit dysregulated transforming growth factor-β and lack mural cell development.
Aortic Root Dilatation in Adults with Surgically Repaired Tetralogy of Fallot
Authors: Mongeon François-Pierre , Gurvitz Michelle Z. , Broberg Craig S. , Aboulhosn Jamil , Opotowsky Alexander R. , Kay Joseph D. , Valente Anne Marie , Earing Michael G. , Lui George K. , Fernandes Susan M. , Gersony Deborah R. , Cook Stephen C. , Ting Jennifer Grando , Nickolaus Michelle J. , Landzberg Michael J. , Khairy Paul
Published: December 2012

Background—

Although aortic root pathology has been described in patients with tetralogy of Fallot, the scope of the problem remains poorly defined. We sought to determine the prevalence and predictors of aortic root dilatation in adults with repaired tetralogy of Fallot.

Methods and Results—

A multicenter cross-sectional study was conducted with standardized reassessment of echocardiographic parameters in 474 adults (≥18 years) with surgically repaired tetralogy of Fallot or pulmonary atresia with ventricular septal defect. The aortic root was measured in a parasternal long-axis view, in diastole, at the level of the sinus of Valsalva. Prevalence and predictors of an absolute diameter ≥40 mm and of an observed-to-expected ratio >1.5 were assessed. The aortic root dimension was ≥40 mm in 28.9% (95% confidence interval, 26.9%–30.9%). In multivariate analyses, the only independently associated factor was male sex (odds ratio, 4.48; 95% confidence interval, 1.55–12.89;
P
=0.006). The prevalence of an observed-to-expected aortic root dimension ratio >1.5 was 6.6% (95% confidence interval, 5.3%–7.9%). It was associated with pulmonary atresia and moderate or severe aortic regurgitation in univariate analyses, but no independent predictor was identified. The side of the aortic arch was not associated with aortic root dimension. The prevalence of moderate or severe aortic regurgitation was 3.5% (95% confidence interval, 2.7%–4.2%).

Conclusions—

Although nearly one third of adults with repaired tetralogy of Fallot have an aortic root diameter ≥40 mm, the prevalence of a dilated aortic root, when defined by an indexed ratio of observed-to-expected values, is low. Similarly, moderate or severe aortic regurgitation is uncommon.
Long-Term Mortality Data From the Balloon Pump–Assisted Coronary Intervention Study (BCIS-1)
Authors: Perera Divaka , Stables Rod , Clayton Tim , De Silva Kalpa , Lumley Matthew , Clack Lucy , Thomas Martyn , Redwood Simon
Published: December 2012

Background—

There is conflicting evidence on the utility of elective intra-aortic balloon pump (IABP) use during high-risk percutaneous coronary intervention (PCI). Observational series have indicated a reduction in major in-hospital adverse events, although randomized trial evidence does not support this. A recent study has suggested a mortality benefit trend early after PCI, but there are currently no long-term outcome data from randomized trials in this setting.

Methods and Results—

Three hundred one patients with left ventricular impairment (ejection fraction <30%) and severe coronary disease (BCIS-1 jeopardy score ≥8; maximum possible score=12) were randomized to receive PCI with elective IABP support (n=151) or without planned IABP support (n=150). Long-term all-cause mortality was assessed by tracking the databases held at the Office of National Statistics (in England and Wales) and the General Register Office (in Scotland). The groups were balanced in terms of baseline characteristics (left ventricular ejection fraction, 23.6%; BCIS-1 jeopardy score, 10.4) and the amount and type of revascularization performed. Mortality data were available for the entire cohort at a median of 51 months (interquartile range, 41–58) from randomization. All-cause mortality at follow-up was 33% in the overall cohort, with significantly fewer deaths occurring in the elective IABP group (n=42) than in the group that underwent PCI without planned IABP support (n=58) (hazard ratio, 0.66; 95% confidence interval, 0.44–0.98;
P
=0.039).

Conclusions—

In patients with severe ischemic cardiomyopathy treated with PCI, all-cause mortality was 33% at a median of 51 months. Elective IABP use during PCI was associated with a 34% relative reduction in all-cause mortality compared with unsupported PCI.

Clinical Trial Registration—

URL:
http://www.isrctn.org
. Unique identifier: ISRCTN40553718; and
http://www.clinicaltrials.gov
. Unique identifier: NCT00910481.
Physical Activity and Risk of Cerebrovascular Disease in the European Prospective Investigation Into Cancer and Nutrition-Spain Study
Authors: Huerta José María , Chirlaque María-Dolores , Tormo María-José , Gavrila Diana , Arriola Larraitz , Moreno-Iribas Conchi , Amiano Pilar , Ardanaz Eva , Barricarte Aurelio , Dorronsoro Miren , Egüés Nerea , Larrañaga Nerea , Molina-Montes Esther , Quirós José Ramón , Sánchez María-José , González Carlos A. , Navarro Carmen
Published: December 2012

Background and Purpose—

Large-scale prospective epidemiological data testing the association between physical activity (PA) and cerebrovascular diseases (CVDs) are scarce, particularly in Europe. The objective was to assess the risk of CVD according to PA levels in adults.

Methods—

We included a total of 13 576 men and 19 416 women aged 29 to 69 years and participating in the European Prospective Investigation into Cancer and Nutrition cohort in Spain, recruited between 1992 and 1996 and followed-up until 2006 to ascertain incident CVD events. The validated European Prospective Investigation into Cancer and Nutrition PA questionnaire was used to assess metabolic equivalent × hours per week dedicated to different types of PA. Hazard ratios of CVD by PA levels were estimated using multivariate Cox regression. Extensive baseline data collected on diet, lifestyle habits, medical history, and anthropometry were available to adjust for.

Results—

A total of 210 transient ischemic attacks and 442 stroke cases (80% ischemic, 10% hemorrhagic, 7% subarachnoid hemorrhage, and 3% mixed or unspecified) were registered after 12.3 years of mean follow-up. Recreational activity was inversely associated with risk of CVD in women but not in men. Women walking for ≥3.5 hours per week were at lower risk of stroke than those who did not engage in regular walking. No significant associations were found for other leisure time activities or vigorous PA with CVD in either sex.

Conclusions—

Recreational PA of moderate intensity was inversely associated with stroke incidence in women, whereas PA showed no effect on CVD risk in men. Increasing time dedicated to activities such as walking would be expected to help to reduce the stroke burden in women.
Is Intra-Arterial Thrombolysis Beneficial for M2 Occlusions? Subgroup Analysis of the PROACT-II Trial
Authors: Rahme Ralph , Abruzzo Todd A. , Martin Renee’ Hebert , Tomsick Thomas A. , Ringer Andrew J. , Furlan Anthony J. , Carrozzella Janice A. , Khatri Pooja
Published: December 2012

Background and Purpose—

The role of endovascular therapy for acute M2 trunk occlusions is debatable. Through a subgroup analysis of Prolyse in Acute Cerebral Thromboembolism-II, we compared outcomes of M2 occlusions in treatment and control arms.

Methods—

Solitary M2 occlusions were identified from the Prolyse in Acute Cerebral Thromboembolism-II database. Primary endpoints were successful angiographic reperfusion (TICI 2–3) at 120 minutes and functional independence (mRS 0–2) at 90 days.

Results—

Forty-four patients with solitary M2 occlusions, 30 in the treatment arm and 14 in the control arm, were identified. Successful reperfusion (TICI 2–3) was achieved in 53.6% and 16.7% of patients in the treatment and control arms, respectively (
P
=0.04). A favorable clinical outcome (mRS 0–2) was observed in 53.3% and 28.6%, respectively (
P
=0.19). Baseline characteristics were similar between the 2 groups.

Conclusions—

Intra-arterial thrombolysis may lead to a 3-fold increase in the rate of early reperfusion of solitary M2 occlusions and could potentially double the chance of a favorable functional outcome at 90 days.

Clinical Trial Registration—

This trial was not registered because enrollment began before July 1, 2005.
Clusters of Spreading Depolarizations Are Associated With Disturbed Cerebral Metabolism in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Sakowitz Oliver W. , Santos Edgar , Nagel Alexandra , Krajewski Kara L. , Hertle Daniel N. , Vajkoczy Peter , Dreier Jens P. , Unterberg Andreas W. , Sarrafzadeh Asita S.
Published: December 2012

Background and Purpose—

We studied the dynamics of extracellular brain tissue concentrations of glucose, lactate, pyruvate, and glutamate during the occurrence of spreading depolarizations (SDs) in patients with aneurysmal subarachnoid hemorrhage.

Methods—

In this prospective observational study, patients with aneurysmal subarachnoid hemorrhage received multimodal cerebral monitoring, including intracranial pressure, cerebral microdialysis, and subdural electrocorticography.

Results—

Seven of the 17 recruited patients had intracerebral hemorrhage, acute ischemia and severe brain oedema leading to acute ischemic neurological deficits associated with early disturbance of metabolism at the recording site. They displayed a total of 130 SDs. The remaining 10 patients without acute ischemic neurological deficits exhibited 138 single SDs and 68 SDs in clusters. In patients without acute ischemic neurological deficits, clustered SDs were associated with a significant transient decrease in glucose and increase in lactate compared with baseline during the first 140 minutes after SDs. Moreover, the number of clustered SDs correlated with the outcome (
R
=−0.659;
P
<0.01).

Conclusion—

SDs can propagate in nonischemic human brain tissue. Clusters of SDs are related to metabolic changes suggestive of ongoing secondary damage in primarily nonischemic brain tissue.
Development of a GOES-R Advanced Baseline Imager Solar Channel Radiance Simulator for Ice Clouds
Authors: Ding Shouguo , Yang Ping , Baum Bryan A. , Heidinger Andrew , Greenwald Thomas
Published: December 2012

This paper describes the development of an ice cloud radiance simulator for the anticipated Geostationary Operational Environmental Satellite R (GOES-R) Advanced Baseline Imager (ABI) solar channels. The simulator is based on the discrete ordinates radiative transfer (DISORT) model. A set of correlated k-distribution (CKD) models is developed for the ABI solar channels to account for atmospheric trace gas absorption. The CKD models are based on the ABI spectral response functions and also consider when multiple gases have overlapping absorption. The related errors of the transmittance profile are estimated on the basis of the exact line-by-line results, and it is found that errors in transmittance are less than 0.2% for all but one of the ABI solar channels. The exception is for the 1.378-μm channel, centered near a strong water vapor absorption band, for which the errors are less than 2%. For ice clouds, the band-averaged bulk-scattering properties for each ABI [and corresponding Moderate Resolution Imaging Spectroradiometer (MODIS)] solar channel are derived using an updated single-scattering property database of both smooth and severely roughened ice particles, which include droxtals, hexagonal plates, hexagonal hollow and solid columns, three-dimensional hollow and solid bullet rosettes, and several types of aggregates. The comparison shows close agreement between the radiance simulator and the benchmark model, the line-by-line radiative transfer model (LBLRTM)+DISORT model. The radiances of the ABI and corresponding MODIS measurements are compared. The results show that the radiance differences between the ABI and MODIS channels under ice cloud conditions are likely due to the different band-averaged imaginary indices of refraction.
Simulation of Heavy Lake-Effect Snowstorms across the Great Lakes Basin by RegCM4: Synoptic Climatology and Variability
Authors: Notaro Michael , Zarrin Azar , Vavrus Steve , Bennington Val
Published: December 2012

A historical simulation (1976–2002) of the Abdus Salam International Centre for Theoretical Physics Regional Climate Model, version 4 (ICTP RegCM4), coupled to a one-dimensional lake model, is validated against observed lake ice cover and snowfall across the Great Lakes Basin. The model reproduces the broad temporal and spatial features of both variables in terms of spatial distribution, seasonal cycle, and interannual variability, including climatological characteristics of lake-effect snowfall, although the simulated ice cover is overly extensive largely due to the absence of lake circulations. A definition is introduced for identifying heavy lake-effect snowstorms in regional climate model output for all grid cells in the Great Lakes Basin, using criteria based on location, wind direction, lake ice cover, and snowfall. Simulated heavy lake-effect snowstorms occur most frequently downwind of the Great Lakes, particularly to the east of Lake Ontario and to the east and south of Lake Superior, and are most frequent in December–January. The mechanism for these events is attributed to an anticyclone over the central United States and related cold-air outbreak for areas downwind of Lakes Ontario and Erie, in contrast to a nearby cyclone over the Great Lakes Basin and associated cold front for areas downwind of Lakes Superior, Huron, and Michigan.
Prevalence of Low Ankle Brachial Index and Relationship With Cardiovascular Risk Factors in a Western Urban Population in Turkey
Authors: Sözmen Kaan , Ünal Belgin
Published: December 2012

We determined the prevalence of peripheral arterial disease (PAD) and associated risk factors in an urban population age ≥30 years in Turkey and assessed the impact of incorporating ankle brachial index (ABI) measurement with coronary heart disease risk calculations to the risk reclassification of individuals. The sample was drawn from 4600 participants of Balcova Heart Study. The prevalence of low ABI (<0.9) was 6.3%. Current smoking (odds ratio [OR]: 5.07, 95% confidence interval [CI]: 1.85-13.88), cardiovascular disease history (OR: 6.83, 95% CI: 3.00-15.53), hypertension (OR: 2.58, 95% CI: 1.06-6.33), diabetes (OR: 3.25, 95% CI: 1.51-6.98), and high waist circumference (OR: 2.24, 95% CI: 1.02-4.94) were positively associated with prevalent PAD. When ABI measurement was taken into account, 3.5% of low or intermediate risk patients were reclassified as high risk. Screening individuals who have one of these risk factors with ABI can help reclassifying individuals toward the high-risk category.
Pharmacotherapeutic Considerations for the Use of Prasugrel and Ticagrelor to Reduce Stent Thrombosis in Patients With Acute Coronary Syndrome
Authors: Piccolo Raffaele , Gioia Giuseppe Di , Niglio Tullio , D’Anna Carolina , Rosa Roberta De , Strisciuglio Teresa , Bevilacqua Michele , Piscione Federico , Cirillo Plinio , Galasso Gennaro
Published: December 2012

Despite the improvement in stent technology, stent thrombosis (ST), a potentially catastrophic event, still occurs. Among several risk factors for ST, high on-treatment platelet reactivity to clopidogrel has been demonstrated to play a role, occurring in about one-third of the patients. In order to overcome this limitation, prasugrel and ticagrelor, newer P2Y12 inhibitors, have been developed and approved for clinical use. Two large clinical trials, TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel-thrombolysis in myocardial infarction (TRITON-TIMI) 38 and Study of Platelet Inhibition and Patient Outcomes (PLATO), evaluated these drugs in patients with acute coronary syndrome (ACS), showing a significant improvement in efficacy end points (including a prominent reduction in ST occurrence) compared to clopidogrel. In contrast, the TRILOGY ACS trial found no benefit with prasugrel compared to clopidogrel in patients with medically treated ACS. The aim of this review is to consider decision-making strategies between prasugrel and ticagrelor in daily clinical practice.
Effectiveness of a Shared Leadership Model
Authors: Wister Andrew V. , Beattie B. Lynn , Gallagher Elaine M. , Gutman Gloria M. , Hemingway Dawn , Reid R. Colin , Sinden Danielle , Symes Bobbi
Published: December 2012

This article applies and builds upon the network leadership models introduced by Provan and Kenis to the case of the British Columbia Network for Aging Research (BCNAR). We specify a particular type of shared leadership model and term this a Targeted Shared Leadership (TSL) model based on the governance structure of BCNAR. Key features include six coleaders who are selected on the basis of representation of five major universities (typically in its gerontology center) situated in the five provincial health authorities in British Columbia. Several network characteristics are introduced and then applied to BCNAR to assess effectiveness of the leadership structure. Innovations in research grant capacity support, communication, mentorship and training of new gerontologists, and knowledge translation are used to specify the effectiveness of the leadership structural dynamics of BCNAR. Potential applications of this shared leadership model for other networks are discussed.
Introduction
Authors: Zipp Samuel , Carriere Michael
Published: December 2012

Recent scholarly interest in urban renewal has established its place in the social and political history of the postwar United States. The contributors to this special section argue that equal attention is now needed to the intellectual debates that marked urban renewal’s conception, implementation, and undoing. Investigating renewal’s conflicted origins and untidy demise through the history of ideas can restore some of the historical specificity and contingency to understandings of a policy that has long been portrayed as simply a foreordained failure.
The Roots and Routes of Urban Renewal
Authors: Zipp Samuel
Published: December 2012

This synthetic essay offers a new look at the origins of the ideas that underpinned urban renewal. Recent accounts separate policy history from the cultural influence of modernism in planning and architecture to show how real estate interests and urban planners co-opted the reform energies and social idealism of the modern housing movement and brought private capital downtown. However, understanding the full history of urban renewal requires showing how it was shaped as both policy and idea. This essay traces the intertwined history of campaigns for both slum clearance and modern housing to show how the motives of planning, profit, and reform idealism combined to form both a modernist “ethic of city rebuilding” and an aggressive program for ridding the city of “blight” and restoring property values. Urban renewal was indebted to both, and a full accounting of its history should reveal the tense and productive relations between the two.
Good Partner, Good Parent
Authors: Millings Abigail , Walsh Judi , Hepper Erica , O’Brien Margaret
Published: December 2012

This cross-sectional, dyadic questionnaire study examined the contribution of romantic attachment and responsive caregiving to parenting style, investigating both gender and partner effects. One hundred and twenty-five couples with children aged 7 to 8 years completed measures of attachment styles, responsive caregiving toward partner, and parenting styles. Structural Equation Modeling was used to examine the intra- and interpersonal associations between romantic attachment, caregiving responsiveness, and parenting styles. Attachment avoidance and anxiety were both negatively associated with responsive caregiving to partner, which in turn was positively associated with authoritative (optimal) parenting styles and negatively associated with authoritarian and permissive (nonoptimal) parenting styles. Responsive caregiving mediated all links between attachment and parenting, with an additional direct association between attachment anxiety and nonoptimal parenting styles that was not explained by caregiving responsiveness. Findings are discussed with reference to attachment theory.
A Comparison of the Effectiveness of Varenicline and Transdermal Nicotine Patch in Outpatients Following a Standardized Smoking Cessation Program in Southern Taiwan
Authors: Hsueh Shu-Chun , Hsueh Kuang-Chieh , Chou Ming-Yueh , Tu Ming-Shium
Published: December 2012

`Varenicline use has been shown to produce greater long-term smoking cessation rates than bupropion but has no clear differences compared to the transdermal nicotine patch. We performed this study to compare the effectiveness of varenicline with the nicotine patch at 3 and 6 months of follow-up of patients in an outpatient smoking cessation program provided by a hospital in Southern Taiwan. The sample consisted of 463 patients who attended the smoking cessation program at the outpatient family medicine clinic at Kaohsiung Veterans General Hospital between March 2006 and December 2008. All patients were aged ≥18 years and either smoked ≥10 cigarettes per day or scored ≥4 on the Fagerström Test for Nicotine Dependence. Patients were seen by a physician for up to 8 sessions in 90 days. Medication use was guided by patient preference (208 opted for varenicline and 255 for the nicotine patch). The primary outcomes of the study were self-reported 7-day point prevalence abstinence rates at 3 and 6 months from the first clinic visit. Varenicline users had a significantly higher abstinence rate than those using nicotine patch at 3-month (47.1% vs. 30.6%; odds ratio [OR] = 2.02, 95% confidence interval [CI] = [1.38, 2.96]) and 6-month follow-up (41.3% vs. 30.6%; OR = 1.60, 95% CI [1.09, 2.32]). Both groups had similar incidences of adverse events. Varenicline use in a sample of treatment-seeking-dependent smokers was associated with significantly higher abstinence rates than the nicotine patch.
Vanadium Toxicity in Mice
Authors: Imura Hitomi , Shimada Akinori , Naota Misaki , Morita Takehito , Togawa Masako , Hasegawa Tatsuya , Seko Yoshiyuki
Published: December 2012

Because precise information as to the toxicity of vanadium is required for practical use of vanadium compounds as antidiabetic drugs, we examined vanadium toxicity in mice fed normal diet or high-fat diet (C57BL/6N, male, 7 weeks) by oral administration of ammonium metavanadate (AMV) with a maximum dose of 20 mgV/kg/day. Marked lipid accumulation in hepatocytes, renal epithelial cells, and mucosal epithelial cells of the small and large intestines and severe degeneration, necrosis, and loss of mucosal epithelial cells in the small intestine were observed. These pathological changes were more severe in mice fed high-fat diet than mice fed normal diet, and the intensity of the changes increased with increase in the administered dose of AMV. By electron microscopy, the number and size of lipid droplets in hepatocytes were increased. In the small intestine, a TUNEL assay showed a decreased number of positive cells, and positive cells for acrolein immunohistochemistry were observed specifically in the mucosal epithelial cells indicating degeneration and necrosis in the AMV-treated group, suggesting that a possible factor responsible for cell necrosis in the small intestine could be oxidative stress. In conclusion, AMV may impair cellular lipid metabolism, resulting in lipid accumulation, and induce mucosal epithelial cell necrosis in the small intestine.
Reactive Intermediates
Authors: Monks Terrence J. , Lau Serrine S.
Published: December 2012

Biologically reactive intermediates formed as endogenous products of various metabolic processes are considered important factors in a variety of human diseases, including Parkinson’s disease and other neurological disorders, diabetes and complications thereof, and other inflammatory-associated diseases. Chemical-induced toxicities are also frequently mediated via the bioactivation of relatively stable organic molecules to reactive electrophilic metabolites. Indeed, chemical-induced toxicities have long been known to be associated with the ability of electrophilic metabolites to react with a variety of targets within the cell, including their covalent adduction to nucleophilic residues in proteins, and nucleotides within DNA. Although we possess considerable knowledge of the various biochemical mechanisms by which chemicals undergo metabolic bioactivation, we understand far less about the processes that couple bioactivation to toxicity. Identifying specific sites within a protein, which are targets for adduction, can provide the initial information necessary to determine whether such adventitious posttranslational modifications significantly alter either protein structure and/or function. To address this problem, we have developed mass spectrometry (MS)-based approaches to identify specific amino acid targets of electrophile adduction (electrophile-binding motifs), coupled with molecular modeling of such adducts, to determine the potential structural and functional consequences. Where appropriate, functional assays are subsequently conducted to assess protein function.
Clinical Characteristics of Pediatric Granular Myringitis
Authors: Levi Jessica R. , Ames Julie A. , Gitman Lyuba , Morlet Thierry , O’Reilly Robert C.
Published: December 2012

Objective

To determine the clinical characteristics of children with granular myringitis.

Study Design

Case series with chart review of children with granular myringitis.

Setting

Tertiary care children’s hospitals in Delaware and Florida.

Subjects and Methods

From July 1, 2006, to June 30, 2011, 15 patients were identified with granular myringitis based on International Classification of Diseases, Ninth Revision code 384.1 (10 male, 5 female; 10 left‐sided, 5 right‐sided).

Results

Average age at onset was 10 years (range, 4‐18 years). Average length of symptoms was 21 months (range, 3‐48 months). Thirteen of the 15 patients (87%) had myringotomy tube placement prior to diagnosis of myringitis, and 11 had a previous perforation (73%). Eleven myringoplasties were performed on 8 (53%) patients prior to the onset of granular myringitis (5 fascia, 2 fat, 2 cartilage, 1 paper patch, and 1 at an outside hospital that was unknown). A total of 27 otolaryngologic surgical procedures were done on 14 of 15 patients. Ten patients (67%) had audiometry performed, and 6 (40%) had ear cultures. Medical treatment included ciprofloxacin and dexamethasone otic drops in all patients, oral antibiotics in 4 patients, and additional topical agents in 8 patients. Two patients had laser resurfacing, and 1 patient had surgical curettage. Five patients had long‐term remission, 8 had intermittent remission, and 2 had no remission of their symptoms.

Conclusion

Granular myringitis is a chronic, recalcitrant disease typically preceded by myringotomy and tube placement or myringoplasty/tympanoplasty. Medical and surgical intervention is varied and often does not lead to permanent resolution of the disease.
Government Size, Nonprofit Sector Strength, and Corruption
Authors: Themudo Nuno S.
Published: December 2012

Government should serve the public good. Yet critics argue that “big government” is a major cause of corruption. This article assesses the empirical validity of their argument through cross-national statistical analysis, addressing two of previous research’s key weaknesses: lack of controls for potential reverse causation and for the likely confounding impact of nonprofit sector size. Contrary to critics’ claims, the analysis presented here finds no evidence that a larger government generally contributes to higher corruption. Instead, both government and nonprofit sector size generally have an inverse relationship with the level of corruption. To combat corruption, therefore, public administrators should be skeptical of recommendations for sweeping government cuts and should instead consider policies that strengthen the public and the nonprofit sectors.
Relationship of the Intercondylar Roof and the Tibial Footprint of the ACL
Authors: Scheffel Peter T. , Henninger Heath B. , Burks Robert T.
Published: December 2012

Background:

Debate exists on the proper relation of the anterior cruciate ligament (ACL) footprint with the intercondylar notch in anatomic ACL reconstructions. Patient-specific graft placement based on the inclination of the intercondylar roof has been proposed. The relationship between the intercondylar roof and native ACL footprint on the tibia has not previously been quantified.

Hypothesis:

No statistical relationship exists between the intercondylar roof angle and the location of the native footprint of the ACL on the tibia.

Study Design:

Case series; Level of evidence, 4.

Methods:

Knees from 138 patients with both lateral radiographs and MRI, without a history of ligamentous injury or fracture, were reviewed to measure the intercondylar roof angle of the femur. Roof angles were measured on lateral radiographs. The MRI data of the same knees were analyzed to measure the position of the central tibial footprint of the ACL (cACL). The roof angle and tibial footprint were evaluated to determine if statistical relationships existed.

Results:

Patients had a mean ± SD age of 40 ± 16 years. Average roof angle was 34.7° ± 5.2° (range, 23°-48°; 95% CI, 33.9°-35.5°), and it differed by sex but not by side (right/left). The cACL was 44.1% ± 3.4% (range, 36.1%-51.9%; 95% CI, 43.2%-45.0%) of the anteroposterior length of the tibia. There was only a weak correlation between the intercondylar roof angle and the cACL ( R = 0.106). No significant differences arose between subpopulations of sex or side.

Conclusion:

The tibial footprint of the ACL is located in a position on the tibia that is consistent and does not vary according to intercondylar roof angle. The cACL is consistently located between 43.2% and 45.0% of the anteroposterior length of the tibia. Intercondylar roof–based guidance may not predictably place a tibial tunnel in the native ACL footprint. Use of a generic ACL footprint to place a tibial tunnel during ACL reconstruction may be reliable in up to 95% of patients.
Uptake of copper ions from aqueous solutions by Bacillus strain isolated from desert soil
Authors: Ahmady-Asbchin Salman
Published: December 2012

Biosorption of copper (Cu) ions from aqueous solutions has been studied in a batch system using a Bacillus species AEJ-89 isolated from Maranjab desert soil. The optimum conditions of biosorption were determined by investigating the initial pH, contact time, and the initial concentrations of metal ions at constant temperature (25°C). The maximum biosorption of Cu ions was observed at pH 5.0 ± 0.1. Biosorption equilibrium times for Cu (II) ions were observed in 30 min. The maximum biosorption capacities of Cu (II) ions on Bacillus species AEJ-89 were determined to be 0.48 mmol g−1 at 200 mg l−1 concentration. The experimental adsorption data were fitted to Langmuir isotherm model. The interactions between metal ions and functional groups on the cell wall surface of the biomass were confirmed by Fourier transform infrared spectroscopy analysis. Cu (II) ions were removed from metal-laden biomass after desorption treatments by the addition of different desorbing solutions. The results indicated that the bacterial isolate Bacillus species AEJ-89 is a suitable biosorbent for the removal of Cu (II) ions from aqueous solutions.
Evaluation of standardized Bacopa monniera extract in sodium fluoride-induced behavioural, biochemical, and histopathological alterations in mice
Authors: Balaji Bhaskar , Kumar Ekambaram Prem , Kumar Anil
Published: December 2012

Effect of standardized Bacopa monniera (BM; family: Scrophulariaceae) extract (100 and 300 mg/kg) against sodium fluoride (NaF; 100 and 200 ppm)-induced behavioural, biochemical, and neuropathological alterations in mice was evaluated. Akinesia, rotarod (motor coordination), forced swim test (depression), open field test (anxiety), transfer latency (memory), cholinesterase (ChE), and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) were determined in mice treated with NaF for 30 days alone and in combination with BM. NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice. However, NaF did not alter the weight gain, feed/water consumption, and anxiety profile. Suppression of ChE levels and increased oxidative stress were observed in mice treated with NaF. Coadministration of BM significantly improved the memory, ChE levels, and antioxidant enzymes but failed to alter the fluoride levels in NaF-treated mice. Histopathological studies revealed that BM protected the neuropathological alterations induced by NaF.
The use of endemic Iranian plant, Echium amoenum, against the ethyl methanesulfonate and the recovery of mutagenic effects
Authors: Uysal Handan , Kızılet Halit , Ayar Arif , Taheri Arash
Published: December 2012

In this study, potential genotoxic effects of ethyl methanesulfonate (EMS) that caused mutagenicity in a variety of organisms were tried to resolve by the methanol and chloroform extract of Echium amoenum (EAmet and EAchl) Fisch. & C.A. Mey. from the family of Boraginaceae, which is an endemic plant, and is used as an alternative treatment among public in Iran. Somatic mutation and recombination test with Drosophila wing was used to determine the genotoxic and antigenotoxic effects in our investigations. For this purpose, 3-day-old transheterozygous larvae of mwh/flr3 genotype of Drosophila melanogaster were used in all our experiments. The larvae were fed chronically on the Drosophila instant medium (DIM) including 1 ppm EMS. However, in another application group, different concentrations (1, 2 and 4 ppm) of EAmet and EAchl were added to DIM including 1 ppm EMS (EMS + EAmet and EMS + EAchl). Then, for the matured individuals, wing preparates were prepared within the mediums that include control group that has only DIM, negative control group that contains dimethyl sulfoxide and application groups in different concentrations that contain EMS, EMS + EAmet and EMS + EAchl. Clone induction frequency for the normal wing phenotype of EMS application group was observed to be 2.00. In the EMS + EAmet application group, the value of 1 ppm EAmet is 1.49, value of 2 ppm EAmet is 1.08 and value of 4 ppm EAmet is 0.72; in the EMS + EAchl application group, the value of 1 ppm is EAchl 1.33, value of 2 ppm EAchl is 0.67 and value of 4 ppm EAchl is 0.56 were determined. This decrease observed between EMS and all application groups in terms of total induction frequency is statistically significant ( p < 0.05). These results concluded that chloroform extracts were more effective than the methanol extracts of E. amoenum.
Central Sleep Apnea
Authors: Jain Sejal V. , Simakajornboon Narong , Arthur Todd M.
Published: December 2012

Central sleep apnea is not uncommon in children with neurologic disorders. The mechanisms include increased ventilatory chemosensitivity to carbon dioxide level. Conventional treatments include oxygen, noninvasive ventilation, and in patients with heart failure, improving cardiac output. Here, we present a case of a 9-year-old male with Angelman syndrome, epilepsy, insomnia, and central sleep apnea. The patient was initially evaluated for nighttime awakenings and pauses in breathing. Sustained-release melatonin was used to improve his nighttime awakenings. A polysomnography confirmed central sleep apnea. We saw a reduction in arousals and improvement in insomnia with sustained-release melatonin. On a repeat study, central sleep apnea was improved. We hypothesize that sustained-release melatonin, by improving sleep continuity and reducing arousals, might improve central sleep apnea. Studies are needed to test the hypothesis.