Facile Microwave Assisted Synthesis of Silver Nanostars for Ultrasensitive Detection of Biological Analytes by SERS.

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have been synthesized using the chemical reduction of Ag+ ions by trisodium citrate. This is the first research reporting the synthesis of AgNS using only trisodium citrate as a reducing and stabilizing agent. The key elements of this original synthesis procedure are rapid hydrothermal synthesis of silver nanostars followed by a cooling down procedure by immersion in a water bath. The synthesis was performed in a sealed bottom flask homogenously heated and brought to a boil in a microwave oven. After 60 s, the colloidal solution was cooled down to room temperature by immersion in a water bath at 35 °C. The as-synthesized AgNS were washed by centrifugation and used for SERS analysis of test molecules (methylene blue) as well as biological analytes: pharmaceutical compounds with various Raman cross sections (doxorubicin, atenolol & metoprolol), cell lysates and amino acids (methionine & cysteine). UV-Vis absorption spectroscopy, (Scanning) Transmission Electron Microscopy ((S)TEM) and Atomic Force Microscopy (AFM) have been employed for investigating nanostars' physical properties.

The Role of Circulating Collagen Turnover Biomarkers and Late Gadolinium Enhancement in Patients with Non-Ischemic Dilated Cardiomyopathy.

Background: Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) that is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagen turnover biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis. We sought to evaluate the association between collagen turnover biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM. Method: We conducted a prospective study on 194 patients (48.7 ± 14.3 years of age; 74% male gender) with NIDCM. The inclusion criteria were similar to those for the definition of NIDCM, performed exclusively by CMR: (1) LV dilation with an LV end-diastolic volume (LVEDV) of over 97 mL/m2; (2) global LV dysfunction, expressed as a decreased LVEF of under 45%. CMR was used to determine the presence and extent of LGE. Several collagen turnover biomarkers were determined at diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Results: Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p < 0.001), also being directly correlated with LGE mass (r2 = 0.42; r2 = 0.44; r2 = 0.31; all p < 0.001). Receiver operating characteristic (ROC) analysis revealed a significant ability to diagnose LGE, with an area under the ROC of 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p < 0.0001). Kaplan−Meier analysis showed that at a threshold of >13.8 ng/dL for Gal3 and >97 ng/dL for PICP, they were able to significantly predict outcome (HR = 2.66, p < 0.001; HR = 1.93, p < 0.002). Of all patients, 17% (n = 33) reached the outcome. In multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p = 0.008; p = 0.04). Nonetheless, collagen turnover biomarkers were closely related to HF severity, providing incremental predictive value for severely decreased LVEF of under 30% in patients with NIDCM, beyond that with LGE alone. Conclusions: In patients with NIDCM, circulating collagen turnover biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.

Left Ventricular Geometry and Replacement Fibrosis Detected by cMRI Are Associated with Major Adverse Cardiovascular Events in Nonischemic Dilated Cardiomyopathy.

To investigate the relationship between left ventricular (LV) long-axis strain (LAS) and LV sphericity index (LVSI) and outcomes in patients with nonischemic dilated cardiomyopathy (NIDCM) and myocardial replacement fibrosis confirmed by late gadolinium enhancement (LGE) using cardiac magnetic resonance imaging (cMRI), we conducted a prospective study on 178 patients (48 ± 14.4 years; 25.2% women) with first NIDCM diagnosis. The evaluation protocol included ECG monitoring, echocardiography and cMRI. LAS and LVSI were cMRI-determined. Major adverse cardiovascular events (MACEs) were defined as a composite outcome including heart failure (HF), ventricular arrhythmias (VAs) and sudden cardiac death (SCD). After a median follow-up of 17 months, patients with LGE+ had increased risk of MACEs. Kaplan-Meier curves showed significantly higher rate of MACEs in patients with LGE+ (p < 0.001), increased LVSI (p < 0.01) and decreased LAS (p < 0.001). In Cox analysis, LAS (HR = 1.32, 95%CI (1.54-9.14), p = 0.001), LVSI [HR = 1.17, 95%CI (1.45-7.19), p < 0.01] and LGE+ (HR = 1.77, 95%CI (2.79-12.51), p < 0.0001) were independent predictors for MACEs. In a 4-point risk scoring system based on LV ejection fraction (LVEF) < 30%, LGE+, LAS > -7.8% and LVSI > 0.48%, patients with 3 and 4 points had a significantly higher risk for MACEs. LAS and LVSI are independent predictors of MACEs and provide incremental value beyond LVEF and LGE+ in patients with NIDCM and myocardial fibrosis.

The value of global longitudinal strain and galectin-3 for predicting cardiovascular events in patients with severe aortic stenosis.

AIMS: Left ventricular global longitudinal strain (GLS) was shown to predict outcomes after valve replacement in patients with aortic stenosis (AS). In the current study, we aimed to test the combined use of GLS and a marker of fibrosis - Galectin-3 - for predicting major cardiovascular adverse events (MACEs) in patients with severe AS. MATERIALS AND METHODS: We conducted a prospective study on 42 patients with severe AS and 42 volunteers. Patient evaluation included biochemistry tests, electrocardiogram, 24-hour Holter monitoring, the 6-minute walk test, and echocardiography. Outcomes of AS patients were defined as the composite of MACEs - sudden cardiac death, non-fatal myocardial infarction, sustained ventricular arrhythmias,atrial arrhythmias, and hospitalization for heart failure. RESULTS: Patients with severe AS had lower GLS, and increased levels of both biomarkers compared to the control group. Both biomarkers correlated to echocardiographic parameters such as left ventricular (LV) mass index, relative wall thickness, GLS, as well as with the 6-minute walk test distance, and glomerular filtration rate (eGFR). GLS and NT-proBNP predicted MACEs reasonably well, while Galectin-3 did not, after adjustments for confounding factors. Kaplan-Meier analysis showed that the probability of freedom from MACEs was significant in patients who exhibited lower GLS [HR 2.73 (95% CI 1.01-7.53), p<0.05] and higher levels of NT-proBNP [HR 5.22 (95% CI 1.85- 14.51), p=0.001]. CONCLUSIONS: Among tested parameters, GLS and NT-proBNP were the most reliable predictors of MACEs in patients with severe AS, while Galectin-3 performed more poorly.

Right Atrium Volume Index in Patients with Secondary Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease.

BACKGROUND: Right atrium volume index has recently been described as a quantitative and highly reproducible echocardiographic parameter associated with right ventricle systolic dysfunction in patients with chronic systolic heart failure. The aim of the current study was to assess right atrium remodeling and to establish correlations with echocardiographic parameters of right ventricle systolic and diastolic dysfunction in patients with pulmonary hypertension due to chronic obstructive pulmonary disease (COPD). METHODS: The study was conducted on 40 patients with secondary pulmonary hypertension due to COPD and 40 healthy volunteers (mean age 59 ± 6 years) who submitted to detailed echocardiographic examinations. Plasma levels of the soluble interleukin-1 receptor family member, N-terminal pro-B type natriuretic peptide and galectin-3 were measured in both groups. RESULTS: The right atrium volume index was significantly higher in the test group (45.7 ± 15.3 vs. 25.4 ± 4.0 mL/m(2)) and showed strong correlations to tricuspid annular plane systolic excursion (r = -0.733, p < 0.0001), right ventricle fractional area change (r = -0.662, p < 0.0001), right ventricle ejection fraction (r = -0.741, p < 0.0001), and systolic pulmonary artery pressures (r = 0.721, p < 0.0001). Multivariate analysis facilitated the construction of a linear regression model which showed that right ventricle systolic dysfunction parameters (R(2)-adjusted = 0.62, p < 0.001), elevated systolic pulmonary artery pressure (R(2)-adjusted = 0.52, p < 0.001) and heart failure biomarkers (log-transformed sST2, galectin-3 and N-terminal pro-B type natriuretic peptide) (R(2)-adjusted = 0.41, p < 0.001) were independently associated with right atrium volume index. CONCLUSIONS: Right ventricle systolic dysfunction and elevated systolic pulmonary artery pressure are independently associated with right atrium volume index in patients with pulmonary hypertension due to COPD. KEY WORDS: Echocardiography; Right atrium volume index; Right ventricular diastolic function; Right ventricular systolic function.