bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of PDE5 by Sulindac Sulfide Selectively Induces Apoptosis and Attenuates Oncogenic Wnt/β-Catenin–Mediated Transcription in Human Breast Tumor Cells
Authors: Tinsley Heather N. , Gary Bernard D. , Keeton Adam B. , Lu Wenyan , Li Yonghe , Piazza Gary A. 
Published: April 2011

Abstract
Nonsteroidal anti-inflammatory drugs (NSAID) such as sulindac sulfide (SS) display promising antineoplastic properties, but toxicities resulting from COX inhibition limit their clinical use. Although COX inhibition is responsible for the anti-inflammatory activity of SS, recent studies suggest that phosphodiesterase (PDE) 5 inhibition and activation of cyclic guanosine monophosphate (cGMP) signaling are closely associated with its ability to induce apoptosis of tumor cells. However, the underlying mechanisms responsible for apoptosis induction, factors that influence sensitivity of tumor cells to SS, and the importance of PDE5 for breast tumor cell growth have not been established. Here we show that SS can induce apoptosis of breast tumor cells, which predominantly rely on PDE5 for cGMP hydrolysis but not normal mammary epithelial cells, which rely on PDE isozymes other than PDE5 for cGMP hydrolysis. Inhibition of PDE5 and activation of protein kinase G (PKG) by SS was associated with increased β-catenin phosphorylation, decreased β-catenin mRNA and protein levels, reduced β-catenin nuclear localization, decreased T-cell factor/lymphoid enhancer factor (Tcf/Lef) promoter activity, and decreased expression of Wnt/β-catenin–regulated proteins. Suppression of PDE5 with siRNA or known PDE5 inhibitors was sufficient to selectively induce apoptosis and attenuate β-catenin–mediated transcription in breast tumor cells with minimal effects on normal mammary epithelial cells. These findings provide evidence that SS induces apoptosis of breast tumor cells through a mechanism involving inhibition of PDE5 and attenuation of oncogenic Wnt/β-catenin–mediated transcription. We conclude that PDE5 represents a novel molecular target for the discovery of safer and more efficacious drugs for breast cancer chemoprevention. Cancer Prev Res; 4(8); 1275–84. ©2011 AACR.
Identification of human thrombin-activatable fibrinolysis inhibitor in vascular and inflammatory cells
Authors: Lin Joellen , Garand Mathieu , Zagorac Branislava , Schadinger Steven , Scipione Corey , Koschinsky Marlys , Boffa Michael 
Published: April 2011

SummaryTAFI (thrombin-activatable fibrinolysis inhibitor) is a carboxypeptidase zymogen originally identified in plasma. The TAFI pathway helps to regulate the balance between the coagulation and fibrinolytic cascades. Activated TAFI (TAFIa) can also inactivate certain pro-inflammatory mediators, suggesting that the TAFI pathway may also regulate communication between coagulation and inflammation. Expression in the liver is considered to be the source of plasma TAFI. TAFI has also been identified in platelets and CPB2 (the gene encoding TAFI) mRNA has been detected in megakaryocytic cell lines as well as in endothelial cells. We have undertaken a quantitative analysis of CPB2 mRNA and TAFI protein in extrahepatic cell types relevant to vascular disease. Using RT-PCR and quantitative RT-PCR, we detected CPB2 mRNA in the human megakaryoblastic cell lines MEG-01 and Dami, the human monocytoid cell line THP-1 as well as THP-1 cells differentiated into a macrophage-like phenotype, and in primary human umbilical vein and coronary artery endothelial cells. CPB2 mRNA abundance in MEG-01, Dami, and THP-1 cells was modulated by the state of differentiation of these cells. Using a recently developed TAFIa assay, we detected TAFI protein in the lysates of the human hepatocellular carcinoma cell line HepG2 as well as in MEG-01 and Dami cells and in the conditioned medium of HepG2 cells, differentiated Dami cells, and THP-1 macrophages. We have obtained clear evidence for extrahepatic expression of TAFI, which has clear implications for the physiological and pathophysiological functions of the TAFI pathway.
High platelet reactivity and clinical outcome – Fact and fiction
Authors: Sibbing Dirk , Byrne Robert A. , Bernlochner Isabell , Kastrati Adnan 
Published: April 2011

SummaryIn patients suffering from acute coronary syndromes or undergoing percutaneous coronary intervention, oral antiplatelet treatment is routinely administered with the primary aim of inhibiting platelet-mediated thrombus formation and subsequent abrupt vessel occlusion. Simultaneous inhibition of blood platelet cyclooxygenase-1 by aspirin and of the P2Y12 receptor by clopidogrel or prasugrel is currently recommended in this setting. Inter-individual response variability to aspirin and especially to clopidogrel is the subject of much debate as evidence has grown over the years linking an attenuated response to treatment with the occurrence of ischaemic events. Consequently, the clinical entity of high (on-treatment) platelet reactivity (HPR) was born and subsequently characterised in numerous studies over the last decade. Until recently, alternative treatment options were limited in patients exhibiting HPR. At present the antiplatelet therapy landscape is changing with the advent of prasugrel and ticagrelor as alternative and more potent treatment options. Different tests for monitoring platelet function are available and are being increasingly employed in research projects and clinical routine. These tests may prove useful for achieving optimal platelet inhibition for the individual patient, and several centres now incorporate such testing in day-to-day practice. Widespread adoption of this practice and incorporation into clinical guidelines awaits the results of ongoing trials in which treatment is changed based on platelet function monitoring. This review aims to summarise available facts and fiction in relation to platelet function testing and reactivity with a particular focus on P2Y12 receptor inhibition in patients undergoing coronary stent placement.
Short-term effects of the smoke-free legislation on haemostasis and systemic inflammation due to second hand smoke exposure
Authors: Cayla Guillaume , Sie Pierre , Silvain Johanne , Brugier Delphine , Cambou Jean-Pierre , Thomas Daniel , Pena Ana , O’Connor Stephen , Bura Alessandra , Ruidavets Jean-Bernard , Collet Jean-Philippe , Montalescot Gilles 
Published: April 2011

SummaryIt was the objective of this study to assess the effect of the implementation of the smoke-free legislation on haemostasis and systemic inflammation in second-hand smoking (SHS)-exposed healthy volunteers. Fibrin-rich clot properties, platelet reactivity and inflammatory biomarkers were measured before and four months following the implementation of the smoke-free legislation in gender and age-matched healthy volunteers exposed (n=23, exposed) and unexposed (n=23, controls) to occupational SHS. The primary objective was to compare fibrin-rich clot stiffness before and after implementation of the smoke-free legislation. There was 40% reduction in fibrin-rich clot stiffness following the implementation of the smoke-free legislation in SHS-exposed volunteers (17 ± 7 vs. 10.6 ± 7 dynes/cm², before and after, respectively, p=0.001). These dramatic changes were associated with a 20% reduction in fibrin fiber density (p<0.01) and a 20% reduction inclot lysis time (p=0.05). No change in fibrin properties was observed in the control group of SHS-unexposed volunteers related to the implementation of the smoke-free legislation. Of interest, neither platelet reactivity nor systemic inflammatory biomarkers were changed in either group. The smoke-free legislation is associated with significant changes in fibrin-rich clot properties toward a less thrombogenic conformation with a better fibrinolysis response while neither platelet reactivity nor systemic inflammatory biomarkers are modified. These improvements may explain the observed reduction in acute coronary syndrome following the implementation of the smoke-free legislation.
Influence of Physical Activity and Screen Time on the Retinal Microvasculature in Young Children
Authors: Gopinath Bamini , Baur Louise A. , Wang Jie Jin , Hardy Louise L. , Teber Erdahl , Kifley Annette , Wong Tien Y. , Mitchell Paul 
Published: April 2011

Objective—
It is not clear whether physical activity and sedentary behavior affect retinal microvascular caliber. We investigated associations among physical activity (outdoor and indoor sporting activities), sedentary behaviors (including screen time, television [TV] viewing, and computer and videogame usage), and retinal microvascular caliber in schoolchildren.

Methods and Results—

Six-year-old students (1765/2238) from a random cluster sample of 34 Sydney schools were examined. Parents completed questionnaires about physical and sedentary activities. Retinal images were taken, and retinal vessel caliber was quantified. After adjusting for age, sex, ethnicity, eye color, axial length, body mass index, birth weight, and mean arterial blood pressure, children who spent more time in outdoor sporting activities (in the highest tertile of activity) had 2.2 μm (95% CI 0.65 to 3.71) wider mean retinal arteriolar caliber than those in the lowest tertile (
P
trend
=0.004). Increasing quartiles of time spent watching TV were associated with narrower mean retinal arteriolar caliber ≈2.3 μm (95% CI 0.73 to 3.92),
P
trend
=0.003.

Conclusion—
These data suggest that physical activity could have a beneficial influence, whereas screen time has a potential adverse influence on retinal microvascular structure. The magnitude of arteriolar narrowing associated with each hour daily of TV viewing is similar to that associated with a 10-mm Hg increase in systolic blood pressure in children.
Targeted Imaging of the Spatial and Temporal Variation of Matrix Metalloproteinase Activity in a Porcine Model of Postinfarct Remodeling
Authors: Sahul Zakir H. , Mukherjee Rupak , Song James , McAteer Jarod , Stroud Robert E. , Dione Donald P. , Staib Lawrence , Papademetris Xenophon , Dobrucki Lawrence W. , Duncan James S. , Spinale Francis G. , Sinusas Albert J. 
Published: April 2011

Background—
Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction after MI remain undefined.

Methods and Results—

MI was surgically induced in pigs (n=23) and cine magnetic resonance (MR) and dual-isotope hybrid single-photon emission CT (SPECT)/CT imaging obtained using thallium-201 and a technetium-99m-labeled MMP targeted tracer (
99m
Tc-RP805) at 1, 2, and 4 weeks post-MI along with controls (n=5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial
99m
Tc-RP805 retention. MMP activation as assessed by in vivo and ex vivo
99m
Tc-RP805 imaging and retention studies was increased nearly 4-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y=31.34e
0.48x
,
P
=0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional
99m
Tc-RP805 uptake and ex vivo MMP-2 activity.

Conclusions—

A novel, multimodality, noninvasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased
99m
Tc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of thallium-201 perfusion. The
99m
Tc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling.
Real-World Lessons From the Implementation of a Depression Screening Protocol in Acute Myocardial Infarction Patients
Authors: Smolderen Kim G. , Buchanan Donna M. , Amin Alpesh A. , Gosch Kensey , Nugent Karen , Riggs Lisa , Seavey Geri , Spertus John A. 
Published: April 2011

Background—
The American Heart Association (AHA) statement has recommended routine screening for depression in coronary artery disease with a 2-stage implementation of the Patient Health Questionnaire (PHQ). Because there is little evidence on feasibility, accuracy, and impact of such a program on depression recognition in coronary patients, the AHA recommendation has met substantial debate and criticism.

Methods and Results—

Before the AHA statement was released, the Mid America Heart and Vascular Institute (MAHVI) had implemented a depression screening protocol for patients with acute myocardial infarction that was virtually identical to the AHA recommendations. To (1) evaluate this MAHVI quality improvement initiative, (2) compare MAHVI depression recognition rates with those of other hospitals, and (3) examine health care providers' implementation feedback, we compared the results of the MAHVI screening program with data from a parallel prospective acute myocardial infarction registry and interviewed MAHVI providers. Depressive symptoms (PHQ-2, PHQ-9) were assessed among 503 MAHVI acute myocardial infarction patients and compared with concurrent depression assessments among 3533 patients at 23 US centers without a screening protocol. A qualitative summary of providers' suggestions for improvement was also generated. A total of 135 (26.8%) eligible MAHVI patients did not get screened. Among screened patients, 90.9% depressed (PHQ-9 ≥10) patients were recognized. The agreement between the screening and registry data using the full PHQ-9 was 61.5% for positive cases (PHQ-9 ≥10) but only 35.6% for the PHQ-2 alone. Although MAHVI had a slightly higher overall depression recognition rate (38.3%) than other centers not using a depression screening protocol (31.5%), the difference was not statistically significant (
P
=0.31). Staff feedback suggested that a single-stage screening protocol with continuous feedback could improve compliance.

Conclusions—
In this early effort to implement a depression screening protocol, a large proportion of patients did not get screened, and only a modest impact on depression recognition rates was realized. Simplifying the protocol by using the PHQ-9 alone and providing more support and feedback may improve the rates of depression detection and treatment.
Comparison of physio ball and plinth trunk exercises regimens on trunk control and functional balance in patients with acute stroke: a pilot randomized controlled trial
Authors: Karthikbabu S , Nayak Akshatha , Vijayakumar K , Misri ZK , Suresh BV , Ganesan Sailakshmi , Joshua Abraham M 
Published: April 2011

Objective: To examine the effects of trunk exercises performed using the physio ball as against the plinth, on trunk control and functional balance in patients with acute stroke. Design: An observer-blinded pilot randomized controlled trial. Subjects: Thirty patients with acute stroke (mean post-stroke duration 12 (95% confidence interval (CI) 2–34) days) who had the first onset of unilateral haemorrhagic or ischaemic lesion and an independent ability to sit for 30 seconds. Setting: Inpatient stroke rehabilitation centre. Interventions: The experimental group performed task-specific trunk exercises on an unstable surface (physio ball) while the control group performed them on a stable surface (plinth). In addition to regular acute physiotherapy, both the groups underwent 1 hour of trunk exercises a day, four days a week for three weeks. Main measures: Trunk Impairment Scale and Brunel Balance Assessment. Results: The difference between the baseline characteristics of the patients belonging to both groups was not statistically significant. Post-intervention, both the groups improved on trunk control and functional balance but the experimental group improved more significantly than the control group (change scores of between-group comparison for the total Trunk Impairment Scale 3.06 (1.43), dynamic sitting balance 1.47 (1.36) and coordination 1.3 (0.67) subscales of Trunk Impairment Scale; the total Brunel Balance Assessment 1.8 (1.4) and stepping 1.87 (1.6) component of Brunel Balance Assessment). The level of significance was set at P < 0.05. Conclusions: The trunk exercises performed on the physio ball are more effective than those performed on the plinth in improving both trunk control and functional balance in acute stroke patients, suggesting a task-specific effect and also a carry-over effect.
The development of a clinical management algorithm for early physical activity and mobilization of critically ill patients: synthesis of evidence and expert opinion and its translation into practice
Authors: Hanekom Susan , Gosselink Rik , Dean Elizabeth , van Aswegen Helena , Roos Ronel , Ambrosino Nicolino , Louw Quinette 
Published: April 2011

Objective: To facilitate knowledge synthesis and implementation of evidence supporting early physical activity and mobilization of adult patients in the intensive care unit and its translation into practice, we developed an evidence-based clinical management algorithm. Methods: Twenty-eight draft algorithm statements extracted from the extant literature by the primary research team were verified and rated by scientist clinicians ( n = 7) in an electronic three round Delphi process. Algorithm statements which reached a priori defined consensus – semi-interquartile range <0.5 – were collated into the algorithm. Results: The draft algorithm statements were edited and six additional statements were formulated. The 34 statements related to assessment and treatment were grouped into three categories. Category A included statements for unconscious critically ill patients; Category B included statements for stable and cooperative critically ill patients, and Category C included statements related to stable patients with prolonged critical illness. While panellists reached consensus on the ratings of 94% (32/34) of the algorithm statements, only 50% (17/34) of the statements were rated essential. Conclusion: The evidence-based clinical management algorithm developed through an established Delphi process of consensus by an international inter-professional panel provides the clinician with a synthesis of current evidence and clinical expert opinion. This framework can be used to facilitate clinical decision making within the context of a given patient. The next step is to determine the clinical utility of this working algorithm.
Arthroscopic Bankart Repair Combined with Remplissage Technique for the Treatment of Anterior Shoulder Instability with Engaging Hill-Sachs Lesion
Authors: Zhu Yi-Ming , Lu Yi , Zhang Jin , Shen Jie-Wei , Jiang Chun-Yan 
Published: April 2011

Background Engaging Hill-Sachs lesions are known to be a risk factor for recurrence dislocation after arthroscopic repair in patients with anterior shoulder instability. For a large engaging Hill-Sachs lesion, arthroscopic remplissage is a solution. Hypothesis Arthroscopic Bankart repair combined with the Hill-Sachs remplissage technique can achieve good results without significant impairment of shoulder function. Study Design Case Series; Level of evidence, 4. Methods Forty-nine consecutive patients who underwent arthroscopic Bankart repair and Hill-Sachs remplissage for anterior shoulder instability were followed up for a mean duration of 29.0 months (range, 24-35 months). There were 42 males and 7 females with a mean age of 28.4 years (range, 16.7-54.7 years). All patients had diagnosed traumatic unidirectional anterior shoulder instability with a bony lesion of glenoid and an engaging Hill-Sachs lesion. Physical examination, radiographs, and magnetic resonance imaging were performed during postoperative follow-up. The American Shoulder and Elbow Surgeons (ASES) score, Constant score, and Rowe score were used to evaluate shoulder function. Results The active forward elevation increased a mean of 8.0° (range, -10° to 80°) postoperatively. However, the patients lost 1.9° (range, -40° to 30°) of external rotation to the side. Significant improvement was detected with regard to the ASES score (84.7 vs 96.0, P < .001), Constant score (93.3 vs 97.8, P = .005), and Rowe score (36.8 vs 89.8, P < .001). There were 1 redislocation, 2 subluxations, and 1 patient with a positive apprehension test; the overall failure rate was 8.2% (4 of 49). Successful healing of the infraspinatus tendon within the Hill-Sachs lesion was shown by magnetic resonance imaging. Conclusion Arthroscopic Bankart repair combined with Hill-Sachs remplissage can restore shoulder stability without significant impairment of shoulder function in patients with engaging Hill-Sachs lesions.
Identification of biomarkers for diagnosis and progression of MS by MALDI-TOF mass spectrometry
Authors: Teunissen CE , Koel-Simmelink MJA , Pham TV , Knol JC , Khalil M , Trentini A , Killestein J , Nielsen J , Vrenken H , Popescu V , Dijkstra CD , Jimenez CR 
Published: April 2011

Introduction: Body fluid biomarkers for clinical subtyping and monitoring of disease progression are of considerable interest in multiple sclerosis (MS). Proteomics tools are optimal for the unbiased simultaneous detection of large series of peptides and proteins. Objectives: To identify novel candidate biomarkers discriminating patients with MS from patients with other neurological diseases (OND), and for subtyping of relapsing–remitting (RR), secondary progressive (SP) and primary progressive (PP) MS patients using a high-throughput MALDI-TOF-based mass spectrometry method. Methods: Paired cerebrospinal fluid (CSF) and serum samples of 41 RRMS, 30 SPMS, 13 PPMS patients and 25 patients with OND were analysed. Results: Out of a total of 100 detected peptides in CSF and 200 peptides in serum, 11 peptides were differentially regulated in serum and two in CSF between patients with MS and the OND control group. Eleven peptides were differentially regulated in both serum and CSF between relapse-onset MS and PPMS patients. Lastly, four peptides were differentially regulated in serum and two in CSF between RRMS and SPMS patients. Specific peaks regulated in MS were tentatively identified as fragments of secretogranin III and complement C3. The peak intensity of the CSF peptide ion with m/z value 8607.7 correlated to atrophy ( r = −0.27, p < 0.005), black hole volumes ( r = 0.31, p < 0.008) and total lesion load ( r = 0.34, p < 0.003). A serum peptide with m/z value of 872.4 elevated in SPMS correlated to Expanded Disability Status Scale ( r = 0.341, p < 0.005) and atrophy ( r = −0.286, p < 0.028). Conclusions: Using high-throughput body fluid profiling by MALDI-TOF mass spectrometry, small proteins and peptides were detected as promising candidate biomarkers for diagnosis and disease progression of MS.