An extensible density-biasing approach for molecular simulations of multicomponent block copolymers.

A node-density biased Monte Carlo methodology is proposed for the molecular structure generation of complex block copolymers. Within this methodology, the block copolymer is represented as bead-spring model. Using self-consistent field theory, a density field for all monomer species within the system is calculated. Block copolymers are generated by random walk configuration biased by the density fields. The proposed algorithm then modifies the generation process by taking the global structure of the polymer into account. It is then demonstrated that these global considerations can be built into the sampling procedure, specifically through functions that assign a permissible difference in density field value between relevant monomer species to each step of the random walk. In this way, the random walk may be naturally controlled to provide the most appropriate conformations. The overall viability of this approach has been demonstrated by using the resulting configurations in molecular dynamics simulations. This new methodology is demonstrated to be powerful enough to generate molecular configurations for a much wider variety of materials than the original approach. Two key examples of the new capabilities of the method are viable configurations for ABABA pentablock copolymers and ABC triblock terpolymers.

N-Terminal Pro-Brain Natriuretic Peptide and Right Ventricular Diameter Are Related to Aspirin Resistance in Coronary Artery Disease Patients.

Background and Objectives: Resistance to ASA (ASAres) is a multifactorial phenomenon defined as insufficient reduction of platelet reactivity through incomplete inhibition of thromboxane A2 synthesis. The aim is to reassess the prevalence and predictors of ASAres in a contemporary cohort of coronary artery disease (CAD) patients (pts) on stable therapy with ASA, 75 mg o.d. Materials and Methods: We studied 205 patients with stable CAD treated with daily dose of 75 mg ASA for a minimum of one month. ASAres was defined as ARU (aspirin reaction units) ≥550 using the point-of-care VerifyNow Aspirin test. Results: ASAres was detected in 11.7% of patients. Modest but significant correlations were detected between ARU and concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.144; p = 0.04), body weight, body mass index, red blood cell distribution width, left ventricular mass, and septal end-systolic thickness, with trends for left ventricular mass index and prothrombin time. In multivariate regression analysis, log(NT-proBNP) was identified as the only independent predictor of ARU-partial r = 0.15, p = 0.03. Median concentrations of NT-proBNP were significantly higher in ASAres patients (median value 311.4 vs. 646.3 pg/mL; p = 0.046) and right ventricular diameter was larger, whereas mean corpuscular hemoglobin concentration was lower as compared to patients with adequate response to ASA. Conclusions: ASAres has significant prevalence in this contemporary CAD cohort and NT-proBNP has been identified as the independent correlate of on-treatment ARU, representing a predictor for ASAres, along with right ventricular enlargement and lower hemoglobin concentration in erythrocytes.

Exceptional oxygen barrier performance of pullulan nanocomposites with ultra-low loading of graphene oxide.

Polymer nanocomposites are increasingly important in food packaging sectors. Biopolymer pullulan is promising in manufacturing packaging films or coatings due to its excellent optical clarity, mechanical strength, and high water-solubility as compared to other biopolymers. This work aims to enhance its oxygen barrier properties and overcome its intrinsic brittleness by utilizing two-dimensional planar graphene oxide (GO) nanoplatelets. It has been found that the addition of only 0.2 wt% of GO enhanced the tensile strength, Young's modulus, and elongation at break of pullulan films by about 40, 44 and 52%, respectively. The light transmittance at 550 nm of the pullulan/GO films was 92.3% and haze values were within 3.0% threshold, which meets the general requirement for food packaging materials. In particular, the oxygen permeability coefficient of pullulan was reduced from 6337 to 2614 mL µm m(-2) (24 h(-1)) atm(-1) with as low as 0.05 wt% of GO loading and further to 1357 mL µm m(-2) (24 h(-1)) atm(-1) when GO concentration reached 0.3 wt%. The simultaneous improvement of the mechanical and oxygen barrier properties of pullulan was ascribed to the homogeneous distribution and prevalent unidirectional alignment of GO nanosheets, as determined from the characterization and theoretical modelling results. The exceptional oxygen barrier properties of pullulan/GO nanocomposites with enhanced mechanical flexibility and good optical clarity will add new values to high performance food packaging materials.

Isocyanate-functionalised graphene oxide and poly(vinyl alcohol) nacre-mimetic inspired freestanding films.

Nacre mimetic films based on 2-ureido-4[1H]-pyrimidinone (UPy) functionalised graphene oxide (GO) and poly(vinyl alcohol) (PVA) were readily prepared by self-assembly using a vacuum filtration method. The isocyanate (UPy) functionalisation of the PVA was confirmed from a combination of Fourier transform infrared spectroscopy (FTIR) and changes in d-spacing from X-ray diffraction (XRD) measurements and, of the GO by solid-state NMR measurements reported by the authors previously. This is the first example of nacre mimetic structures where both the nanoplatelet (GO) and polymer (PVA) components are functionalised with complimentary groups. The resulting films displayed substantial increases in Young's modulus (E) of 392% (GO1/PVA1), ultimate tensile strength (UTS, σ) of 535% (GO1/PVA1), elongation at break (ε max) of 598% (GO10/PVA5) and tensile toughness (U T) of 1789% (GO1/PVA10) compared to the un-functionalised GO analogues. The binding of UPy to both the GO and the PVA provides multiple routes by which these freestanding nacre mimetic films can dissipate applied loads.

Heart-type fatty acid binding protein--a reliable marker of myocardial necrosis in a heterogeneous group of patients with acute coronary syndrome without persistent ST elevation.

BACKGROUND: Myocardial infarction (MI) is one of the most serious challenges of contemporary cardiology. Among biochemical markers, heart-type specific fatty acid binding protein (h-FABP) has a high potential as a marker for the early diagnosis of acute MI. The h-FABP is released early to the bloodstream and may be useful for both rapid confirmation and exclusion of infarction. As opposed to patients with ST segment elevation MI (STEMI), patients with unstable angina (UA)/non-ST segment elevation MI (NSTEMI) present a heterogeneous group in which the confirmation of MI often meets diagnostic difficulties. A rapid, qualitative immunoenzymatic 'point of care' type test, revealing h-FABP in blood, has recently been made available (CardioDetect med). AIM: To evaluate diagnostic value of early measurements of h-FABP and other markers of necrosis (cTnT, CK-MB, CK-MB mass) in a group of 100 patients with an acute coronary syndrome (ACS) without persistent ST segment elevation (NSTE ACS). METHODS: We studied 100 consecutive patients (34 women, 66 men; mean age 61.6 years) with strong suspicion of NSTE ACS and chest pain lasting <24 h before admission. During admission and after 3 and 6 hours patients had measured a panel of conventional biomarkers as well as quantitative measurements of h-FABP (on admission and 3 hours later) using CardioDetect med. The ultimate diagnosis of infarction (NSTEMI) was confirmed in case of a second (6 h after admission) positive quantitative result of cardiac troponin. Non-ST segment elevation MI was finally diagnosed in 56 patients. RESULTS: The comparison of diagnostic utility of all analysed biomarkers of necrosis revealed that h-FABP was superior to other parameters, when measured on admission, and was characterised by 94.7% sensitivity, 100% specificity, 100% positive predictive value, 93.4% negative predictive value and 97% accuracy. Other biomarkers had on admission lower sensitivity - 70.1% for CK-MB mass, 66.7% for CK-MB, 64.9% for cTnT, whereas their specificity was 97.6% for CK-MB mass, 93% for CK-MB and 100% for cTnT. CONCLUSIONS: Qualitative h-FABP test (CardioDetect med) showed excellent sensitivity, higher than measurements of CK-MB mass, CK-MB, and cTnT on hospital admission, and high specificity in the patient group with NSTE ACS. The h-FABP seems to be an excellent biochemical cardiac marker for diagnosing NSTEMI, especially in its early phase, allowing exclusion of myocardial necrosis.

Relative value of serum pregnancy-associated plasma protein A (PAPP-A) and GRACE score for a 1-year prognostication: A complement to calculation in patients with suspected acute coronary syndrome.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) study produced a scale for risk stratification in acute coronary syndromes (ACSs). Pregnancy-associated plasma protein A (PAPP-A) serum concentration was implicated as a marker of unstable atherosclerotic plaques. OBJECTIVES: We hypothesized that the measurement of the concentration of PAPP-A on admission may improve the stratification of cardiovascular risk in suspected ACS patients. MATERIAL AND METHODS: We studied 70 patients with chest pain suggesting ACS diagnosis on admission. Serum cardiac biomarkers and PAPP-A were measured on top of the standard biochemical panel, and the GRACE risk score was calculated. A 12-month follow-up was completed to major adverse cardiac events (MACE): death, myocardial infarction (MI), need for percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG), unplanned cardiovascular hospitalization. RESULTS: In hospital/6-month GRACE, low risk was found in 35 patients (50%)/37 patients (53%), intermediate risk in 23 patients (33%)/21 patients (30%) and high risk in 12 patients (17%)/12 patients (17%). Mean PAPP-A was 39.64 mlU/L (standard deviation - SD 24.2), and median PAPP-A values for in hospital/6-month GRACE were 21.49 mlU/L (quartile 1st; 3rd - 13.41; 32.65) and 22.61 mlU/L (14.03; 34.1) for low risk patients, 51.76 mlU/L (35.18; 59.99) and 51.76 mlU/L (28.9; 62.1) for intermediate risk patients, and 68.82 mlU/L (58.54; 83.76) for high risk patients. The PAAP-A concentration with specific cut-off points had 66.7% positive predictive value (PPV) and 95.5% negative predictive value (NPV) for death, 33.3% PPV and 80.6% NPV for MI, 71.4% PPV and 57.1% NPV for any event. Intermediate and high in hospital/6-months GRACE had 14.3%/15.2% PPV and 100%/100% NPV for death, 34.3%/33.3% PPV and 94.3%/91.9% NPV for MI, 74.3%/72.7% PPV and 65.7%/62.2% NPV for any event. CONCLUSIONS: The PAPP-A serum concentration represents a promising prognostic biomarker with significantly improved PPV. The GRACE score is superior to stratification based on PAPP-A with regard to combined cut-off point for 1-year mortality.

Intrinsic Tuning of Poly(styrene-butadiene-styrene)-Based Self-Healing Dielectric Elastomer Actuators with Enhanced Electromechanical Properties.

The electromechanical properties of a thermoplastic styrene-butadiene-styrene (SBS) dielectric elastomer was intrinsically tuned by chemical grafting with polar organic groups. Methyl thioglycolate (MG) reacted with the butadiene block via a one-step thiol-ene "click" reaction under UV at 25 °C. The MG grafting ratio reached 98.5 mol % (with respect to the butadiene alkenes present) within 20 min and increased the relative permittivity to 11.4 at 103 Hz, with a low tan δ. The actuation strain of the MG-grafted SBS dielectric elastomer actuator was 10 times larger than the SBS-based actuator, and the actuation force was 4 times greater than SBS. The MG-grafted SBS demonstrated an ability to achieve both mechanical and electrical self-healing. The electrical breakdown strength recovered to 15% of its original value, and the strength and elongation at break recovered by 25 and 21%, respectively, after 3 days. The self-healing behavior was explained by the introduction of polar MG groups that reduce viscous loss and strain relaxation. The weak CH/π bonds through the partially charged (δ+) groups adjacent to the ester of MG and the δ- center of styrene enable polymer chains to reunite and recover properties. Intrinsic tuning can therefore enhance the electromechanical properties of dielectric elastomers and provides new actuator materials with self-healing mechanical and dielectric properties.

Laser biostimulation in end-stage multivessel coronary artery disease--a preliminary observational study.

BACKGROUND: Low-energy laser radiation through its direct influence on tissue repair processes without heating effect may have vital importance in the therapy of patients with advanced coronary artery disease (CAD). AIM: The introductory assessment of the effects of laser biostimulation applied to patients with advanced multivessel CAD. METHODS: 39 patients with advanced CAD were assigned (mean age 64.8+/-9.6, male gender 64%, CCS class 2.5+/-0.5, EF=46+/-11%, 69% with a history of acute myocardial infarction), to undergo two sessions of irradiation of low-energy laser light on skin in the chest area from helium-neon B1 lasers. The time of irradiation was 15 minutes while operations were performed 6 days a week for one month. Before including the patients in the experimental group a full clinical evaluation, basic biochemical tests, ECG, 24h Holter recordings, 6-minute walk test, treadmill test using Bruce protocol and full echocardiographic examination were performed. After the first and second period of laser therapy with a one-month break between them analogical parameters with the initial examination were measured. RESULTS: No side effects associated with the laser biostimulation or performed clinical tests were noted. Lower CCS class (2.5+/-0.5 --> 2.2+/-0.4 --> 2.0+/-0.4, p<0.001), higher exercise capacity (5.1+/-2.2 --> 5.8+/-2.2 --> 6.6+/-2.5 [METS], p=0.023), longer exercise time (257+/-126 --> 286+/-127 --> 325+/-156 [s], p=0.06), less frequent angina symptoms during the treadmill test (65% --> 44% --> 38%, p=0.02), longer distance of 6-minute walk test (341+/-93 --> 405+/-113 --> 450+/-109 [m], p <0.001), lower systolic blood pressure values (SP 130+/-14 --> 125+/-12 --> 124+/-14 [mmHg], p=0.05) and trend towards less frequent 1 mm ST depression lasting 1 min during Holter recordings were noted. CONCLUSIONS: An improvement of functional capacity and less frequent angina symptoms during exercise tests without a significant change in the left ventricular function were observed. Laser biostimulation in short-term observation was a very safe method. These encouraging results should be confirmed in a larger, placebo-controlled study.

Predictors of successful acetylsalicylic acid resistance suppression after percutaneous coronary revascularisation.

BACKGROUND AND AIM: There is no established management of resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease (CAD). We hypothesised that simply doubling the usual daily dose of ASA could be effective in overcoming ASA resistance. METHODS: Our study comprised 40 subjects with CAD (male 67.5%, mean age 60.5 ± 8.8 years, mean body mass index 26.9 ± 2.7 kg/m² and median aspirin reaction unit [ARU] value obtained with a Verify Now Aspirin Test 612 [573-634]) with resistance to 75 mg/daily ASA defined as ARU ≥ 550. According to the overcoming of resistance or lack there of in a repeated test after four weeks of 150 mg daily ASA treatment, we defined two subsets: subjects who regained ASA sensitivity, and those who did not. RESULTS: Successful overcoming of ASA resistance was observed in 62.5% of patients. Multivariate analysis regression confirmed that two variables independently determined successful ASA resistance suppression: male gender (OR 6.88; 95% CI 1.29-36.75; p = 0.024), and ARU for 75 mg daily (OR 0.97 per unit at 75 mg; 95% CI 0.94-0.99; p = 0.039). ROC analysis indicated that the threshold value at which ARU at 75 mg ASA treatment was predictive of successful ASA resistance overcoming was ≤ 608 ARU. Using a simple point score (one point for male gender and one for initial ARU ≤ 608), we found that ASA resistance was overcome in 8%, 36% and 56% of patients, when zero, any single, or two predictors were present. CONCLUSIONS: ASA resistance overcoming by dose doubling can be achieved more often in males and in subjects with lower ARU value at ASA 75 mg.

Direct comparison of the diagnostic value of point-of-care tests detecting heart-type fatty acid binding protein or glycogen phosphorylase isoenzyme BB in patients with acute coronary syndromes with persistent ST-segment elevation.

BACKGROUND: Myocardial infarction (MI) with its complications is one of the most serious challenges in contemporary cardiology. Among biochemical markers of myocardial necrosis, heart-type specific fatty acid binding protein (h-FABP) showed excellent sensitivity and specificity for the early diagnosis of an acute MI. The h-FABP is released rapidly (after 30 min) from the cardiomiocyte to the circulation in response to myocardial injury and may be useful for rapid confirmation or exclusion of MI. In recent years, glycogen phosphorylase BB (GP-BB) also emerged as a promising early specific marker of myocardial necrosis. Rapid, qualitative "point of care" tests (POCT) detecting h-FABP (Cardio Detect med) and GP-BB (Diacordon) have recently become available. AIM: To evaluate and compare qualitative POCTs detecting h-FABP and GP-BB in patients with an acute coronary syndrome (ACS). METHODS: We studied 52 patients with a strong suspicion of ACS with persistent ST-segment elevation and chest pain lasting less than 6 hours. The ultimate diagnosis of ST-segment elevation MI (STEMI) was confirmed in case of a second (6 h after admission) positive quantitative result of a cardiac troponin T (cTnT) test. On admission, POCTs to detect both h-FABP and GP-BB were performed. The study population was divided into two groups, with chest pain lasting 〈 3 h (n = 20) or 4-6 h (n = 32). All patients underwent coronary angiography and angioplasty if indicated. The sensitivity of the analysed biomarkers of myocardial necrosis was calculated. RESULTS: The sensitivity of h-FABP (84%) was superior in comparison to the other biomarkers, GP-BB and cTnT, which had sensitivity of 64% and 50%, respectively. Comparison of typical parameters of the diagnostic value of a test (sensitivity, predictive values and accuracy) in both time periods demonstrated that h-FABP was superior to GP-BB. In particular, sensitivity and accuracy of h-FABP was excellent in the group of patients with chest pain lasting 〈 3 h, with sensitivity of 79% for h-FABP and only 47% for GP-BB. Sensitivity and accuracy of cTnT were significantly lower (32% and 35%, respectively). CONCLUSIONS: The h-FABP seems to be an excellent early biomarker of cardiac necrosis in the group of patients with chest pain lasting 〈 3 h. The GP-BB can be also used as a biomarker of myocardic necrosis, but its sensitivity in the early phase of MI is limited.