Controlled Contamination of Epoxy Composites with PDMS and Removal by Laser Ablation

Surface preparation is critical to the performance of adhesively bonded composites. During manufacturing, minute quantities of mold release compounds are inevitably deposited on faying surfaces and may compromise bond performance. To ensure safety, mechanical fasteners and other crack arrest features must be installed in the bondlines of primary structures, which negates some advantages of adhesively bonded construction. Laser ablation is an automated, repeatable, and scalable process with high potential for the surface preparation of metals and composites in critical applications such as primary airframe structures. In this study, laser ablation is evaluated on composite surfaces for the removal of polydimethylsiloxane (PDMS), a common mold release material. Composite panels were contaminated uniformly with PDMS film thicknesses as low as 6.0 nm as measured by variable angle spectroscopic ellipsometry. Bond performance was assessed by mechanical testing using a 250 F cure, epoxy adhesive and compared with pre-bond surface inspection results. Water contact angle, optically stimulated electron emission, and laser induced breakdown spectroscopy were used to characterize contaminated and laser ablated surfaces. The failure mode obtained from double cantilever beam tests correlated well with surface characterization data. The test results indicated that even low levels of PDMS were not completely removed by laser ablation

TCT-737 MONITORING THE LEARNING CURVE AND QUALITY OF CARE IN TAVI PROCEDURES BY CUSUM ANALYSIS

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Percutaneous coronary intervention in an anomalously arising totally occluded circumflex coronary artery

AbstractCongenital coronary anomalies are present in approximately 1% of the patients referred to cardiac catheterization. The present case describes a successful percutaneous coronary intervention in totally occluded left circumflex coronary artery (LCx) with an anomalous origin from right sinus of Valsalva. To the best of our knowledge this is the first case presented of successful recanalization of a chronic total occlusion in an anomalously arising LCx. The case highlights the feasibility of such a challenging procedure on the basis of the knowledge of coronary anatomy and the selection of appropriate guiding catheters and coronary wires

miR-302b enhances breast cancer cell sensitivity to cisplatin by regulating E2F1 and the cellular DNA damage response

The identification of the molecular mechanisms involved in the establishment of the resistant phenotype represents a critical need for the development of new strategies to prevent or overcome cancer resistance to anti-neoplastic treatments.Breast cancer is the leading cause of cancer-related deaths in women, and resistance to chemotherapy negatively affects patient outcomes. Here, we investigated the potential role of miR-302b in the modulation of breast cancer cell resistance to cisplatin.miR-302b overexpression enhances sensitivity to cisplatin in breast cancer cell lines, reducing cell viability and proliferation in response to the treatment. We also identified E2F1, a master regulator of the G1/S transition, as a direct target gene of miR-302b. E2F1 transcriptionally activates ATM, the main cellular sensor of DNA damage. Through the negative regulation of E2F1, miR-302b indirectly affects ATM expression, abrogating cell-cycle progression upon cisplatin treatment. Moreover miR-302b, impairs the ability of breast cancer cells to repair damaged DNA, enhancing apoptosis activation following cisplatin treatment.These findings indicate that miR-302b plays a relevant role in breast cancer cell response to cisplatin through the modulation of the E2F1/ATM axis, representing a valid candidate as therapeutic tool to overcome chemotherapy resistance

po 344 mir 302b as adjuvant therapeutic tool to improve chemotherapy efficacy in human triple negative breast cancer

Introduction MiRNAs are a class of non-coding regulatory RNAs playing key roles in different biological processes including cancer. Triple-negative breast cancer (TNBC) accounts for 15%–20% of all breast cancer cases, with the worst outcome of all subtypes. For TNBC, still lacking targeted therapies, the only therapeutic option is chemotherapy. MiRNAs can modulate chemotherapy response by affecting DNA repair, cell cycle progression, apoptosis and also tumour microenvironment. Macrophages constitute a major component of the immune microenvironment of cancer and pro-tumour M2 macrophages have been associated with response to chemotherapeutic treatments. Here, we investigated the potential of miR-302b as a therapeutic tool to enhance cisplatin sensitivity in a TNBC mouse model and which pathways are involved in this mechanism both in tumour cells and microenvironment. Material and methods TNBC cells were injected into the mammary fat pad of female SCID mice and then treated with lipid nanoparticles containing miR-302b or cel-67 control, alone or in combination with cisplatin. Gene expression profile on collected tumours was performed by microarray. ITGA6 expression was assessed on tumour samples and siRNA tranfection was performed to evaluate the cisplatin response. Tumour sections were stained with anti-arginase 1 (M2 marker) to assess the number of M2 macrophages, and luciferase assay was used to evaluate Irf4 (M2 marker) as a direct target of miR-302b. Results and discussions Our results show that combination of miR-302b with cisplatin significantly impaired tumour growth in comparison with control cel-67. Gene expression profile identified ITGA6 as a regulatory target of miR-302b and cisplatin activity. Indeed, ITGA6 expression is down-modulated in mice treated with miR-302b plus cisplatin compared with control mice. Furthermore, TNBC cell lines increase their cisplatin sensitivity upon ITGA6 silencing. These data confirm the role of ITGA6 in cisplatin response mediated by miR-302b. Moreover, in xenograft tumours collected from the in vivo miR-302b delivery experiment, we observed a reduced number of M2 macrophages in the tumour microenvironment and gene expression confirm immune system modulation. Finally, luciferase assay validate Irf4, a key gene involved in M2 recruitment, as a direct target of miR-302b. Conclusion Our data demonstrate that miR-302b can be exploited as a new therapeutic tool to improve the response to chemotherapy, modulating ITGA6 expression in tumour cells and M2 recruitment in tumour microenvironment

Predictive value of less than moderate residual mitral regurgitation as assessed by transesophageal echocardiography for the short-term outcomes of patients with mitral regurgitation treated with mitral valve repair

<p>Abstract</p> <p>Background</p> <p>Traditionally, in patients with mitral regurgitation (MR) a successful mitral valve repair is considered when residual MR by post-pump transesophageal echocardiography (TEE) is less than moderate or absent. Little is known about the prognostic value of less than moderate (mild or mild-to-moderate) residual MR for the early outcome of patients treated with mitral valve repair.</p> <p>Methods</p> <p>Eligible for this study were patients undergoing isolated mitral valve repair. Patients with moderate or severe residual MR after valve repair were excluded. The primary endpoint of the study was the composite of death or need of reintervention.</p> <p>Results</p> <p>A total of 98 patients (54 with no residual MR-Group 1, and 44 with less than moderate residual MR-Group 2) were analyzed. Of these, 72% presented with New York Heart Association (NYHA) 3/4, and 38% were women. The primary endpoint of the study occurred in 3 (5.5%) patients in Group 1 and 6 (13.6%) patients in Group 2 MR (<it>P </it>= 0.31). There was a trend toward a higher incidence of use of inotropic drugs post-interventional (<it>P </it>= 0.12), and a longer hospital stay among patients with less than moderate residual MR (<it>P </it>= 0.18).</p> <p>Conclusion</p> <p>In our study population, patients with less than moderate residual MR had a trend toward a higher risk of early adverse outcomes as compared with patients with no residual MR by post-pump TEE. Studies with a larger patient population and longer follow-up data may be useful to better define the clinical significance of residual mild MR after mitral vale repair.</p

Influence of involvement of anterior leaflet versus posterior leaflet on residual regurgitation as assessed by transesophageal echocardiography in patients undergoing valve repair for mitral regurgitation due to mitral valve prolapse

<p>Abstract</p> <p>Background</p> <p>Repair of anterior leaflet prolapse is technically more challenging and this might influence outcomes as compared to the repair of posterior leaflet prolapse in patients undergoing surgical correction of mitral regurgitation. We investigated the association of anterior leaflet prolapse with minor residual mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) who underwent valve repair.</p> <p>Methods</p> <p>Eligible for this study were consecutive patients with severe MR due to MVP, who underwent mitral valve repair with residual MR by postpump transesophageal echocardiography ≤2+ during a 20-month period at Pasquinucci Hospital, Massa. Patients undergoing other cardiovascular surgical interventions were excluded. Two groups were defined according to the involvement of mitral valve leaflets: group 1, consisting of patients with anterior leaflet prolapse (isolated or not); and group 2, consisting of patients with isolated posterior leaflet prolapse.</p> <p>Results</p> <p>A total of 70 patients (18 in group 1 and 52 in group 2) were analyzed. Patients in group 2 were younger than those in group 1, but the difference was not significant (P = 0.052). There were no significant differences between the 2 study groups with respect to other variables. The proportion of patients with residual MR 1+/2+ was higher in group 1 than in group 2 (61.1% vs. 32.7%, respectively; P = 0.034). In a logistic regression model, anterior leaflet prolapse was an independent predictor of residual MR 1+/2+ (odds ratio, 4.0; 95% confidence interval, 1.14 to 14.04; P = 0.03).</p> <p>Conclusion</p> <p>In our study population, patients with anterior leaflet prolapse had a higher proportion of residual MR 1+/2+ as compared to those with posterior leaflet prolapse after repair of mitral valve.</p

Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial.

OBJECTIVE  To test the optimal antithrombotic regimen in patients with acute coronary syndrome. DESIGN  Randomised controlled trial. SETTING  Patients with acute coronary syndrome with and without ST segment elevation in 78 centres in Italy, the Netherlands, Spain, and Sweden. PARTICIPANTS  7213 patients with acute coronary syndrome and planned percutaneous coronary intervention: 4010 with ST segment elevation and 3203 without ST segment elevation. The primary study results in the overall population have been reported previously. INTERVENTIONS  Patients were randomly assigned, in an open label fashion, to one of two regimens: bivalirudin with glycoprotein IIb/IIIa inhibitors restricted to procedural complications or heparin with or without glycoprotein IIb/IIIa inhibitors. MAIN OUTCOME MEASURES  Primary endpoints were the occurrence of major adverse cardiovascular events, defined as death, myocardial infarction or stroke; and net adverse clinical events, defined as major bleeding or major adverse cardiovascular events, both assessed at 30 days. Analyses were performed by the principle of intention to treat. RESULTS  Use of a glycoprotein IIb/IIIa inhibitor in patients assigned to heparin was planned at baseline in 30.7% of patients with ST segment elevation, in 10.9% without ST segment elevation, and in no patients assigned to bivalirudin. In patients with ST segment elevation, major adverse cardiovascular events occurred in 118 (5.9%) assigned to bivalirudin and 129 (6.5%) assigned to heparin (rate ratio 0.90, 95% confidence interval 0.70 to 1.16; P=0.43), whereas net adverse clinical events occurred in 139 (7.0%) patients assigned to bivalirudin and 163 (8.2%) assigned to heparin (0.84, 0.67 to 1.05; P=0.13). In patients without ST segment elevation, major adverse cardiovascular events occurred in 253 (15.9%) assigned to bivalirudin and 262 (16.4%) assigned to heparin (0.97, 0.80 to 1.17; P=0.74), whereas net adverse clinical events occurred in 262 (16.5%) patients assigned to bivalirudin and 281 (17.6%) assigned to heparin (0.93, 0.77 to 1.12; P=0.43). CONCLUSIONS  A bivalirudin monotherapy strategy compared with heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.Trial Registration ClinicalTrials.gov NCT01433627