Assessment of plaque vulnerability in carotid atherosclerotic plaques using contrast-enhanced ultrasound.

Background: Atherosclerotic carotid plaques are one of the most important causes of stroke. Apart from the severity of stenosis, there are certain plaque characteristics such as neovascularization and, surface ulceration which makes a plaque vulnerable. This study was performed to study the plaque characteristics using contrast-enhanced ultrasound (CEUS) and evaluate their association with presence of ischemic cerebrovascular symptoms in these patients. Methods: This study included patients presenting at a tertiary care center, having carotid plaques causing >60% stenosis. CEUS was performed for assessment of intraplaque neovascularity and plaque surface characteristics. These plaque features were then evaluated for their association with presence of ischemic cerebrovascular symptoms in patients. Results: Sixty plaques were studied in 50 patients. Thirty-two plaques were associated with ischemic cerebrovascular symptoms. On CEUS, intraplaque neovascularization was seen in 38 of the 60 plaques studied (63.3%). There was statistically significant association of intraplaque neovascularity and plaque surface characteristics with presence of ischemic cerebrovascular symptoms. Conclusion: CEUS allows better characterization of plaque surface characteristics and also depicts plaque neovascularization, which helps in determining the plaque vulnerability. It should be used as an adjunct to ultrasound and doppler assessment of carotid plaques.

Development of Magnesium Oxide-Silver Hybrid Nanocatalysts for Synergistic Carbon Dioxide Activation to Afford Esters and Heterocycles at Ambient Pressure.

Multi-metallic hybrid nancatalysts consisting of a porous metal oxide host and metal satellite guests serve as a scaffold for multi-step transformations of divergent and energy-challenging substrates. Here we have developed a 3D porous MgO framework (Lewis basic host) with Ag0 nanoparticles (noble metal guest) for ambient pressure activation and insertion of CO2 into unsaturated alkyne substrates. The hybrid MgO@Ag-x (x = 2, 5, 7, 8 at % Ag) catalysts are synthesized by impregnating Ag+ ions in porous MgO cubes followed by reduction using NaBH4. Morphological (SEM, TEM, EDX mapping) and structural (PXRD, XPS) characterization reveal that the micron-sized hybrid cubes derive from self-assembly of ~100 nm (edge length) MgO cubes decorated with ~ 5 to 25 nm Ag0 NPs. Detailed XPS analysis illustrates Ag0 is present in two forms, <10 nm NPs and ~25 nm aggregates. The MgO@Ag-7 catalyst is effective for inserting CO2 into aryl alkynes followed by SN2 coupling with allylic chlorides to afford a wide range of ester and lactone heterocycles in excellent yields (61-93%) and with low E-factor (2.8). The proposed mechanism suggests a CO2 capture and substrate assembly role for 3D porous MgO while Ag0 performs the key activation of alkyne and CO2 insertion steps. The catalyst is recyclable (5x) with no significant loss of product yield. Overall, these results demonstrate viable approaches to hybrid catalyst development for challenging conversions such as CO2 utilization in a green and sustainable manner.

Au-Cu@PANI Alloy Core Shells for Aerobic Fibrin Degradation under Visible Light Exposure.

Fibrin plays a critical role in wound healing and hemostasis, yet it is also the main case of cardiovascular diseases and thrombosis. Here, we show the unique design of Au-Cu@PANI alloy core-shell rods for fibrin clot degradation. Microscopic (transmission electron microscopy (TEM), scanning transmission electron microscopy-energy-dispersive X-ray (STEM-EDX)) and structural characterizations (powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS)) of the Au-Cu@PANI hybrid material reveal the formation of Au-Cu heterogeneous alloy core rods (aspect ratio = 3.7) with thin Cu2O and PANI shells that create a positive surface charge (ζ-potential = +22 mV). This architecture is supported by the survey XPS spectrum showing the presence of Cu 2p, N 1s, and C 1s features with binding energies of 934.8, 399.7, and 284.8 eV, respectively. Upon photolysis (λ ≥ 495 or 590 nm), these hybrid composite nanorods provide sufficient excited-state redox potential to generate reactive oxygen species (ROS) for degradation of model fibrin clots within 5-7 h. Detailed scanning electron microscopy (SEM) analysis of the fibrin network shows significant morphology modification including formation of large voids and strand termini, indicating degradation of fibrin protofibril by Au-Cu@PANI. The dye 1,3-diphenylisobenzofuran (DPBF) used to detect the presence of 1O2 shows a 27% bleaching of the absorption at λ = 418 nm within 75 min of irradiation of an aqueous Au-Cu@PANI solution in air. Moreover, electron paramagnetic resonance (EPR) spin-trapping experiments reveal a hyperfine-coupled triplet signature at room temperature with intensities 1:1:1: and g-value = 2.0057, characteristic of the reaction between the spin probe 4-Oxo-TEMP and 1O2 during irradiation. Controlled 1O2 scavenging experiments by NaN3 show 82% reduction in the spin-trapped EPR signal area. Both DPBF bleaching and EPR spin trapping indicate that in situ generated 1O2 is responsible for fibrin strand scission. This unique nanomaterial function via use of ubiquitous oxygen as a reagent could open creative avenues for future in vivo biomedical applications to treat fibrin clot diseases.

Risk factors for development of obesity in an ethnically diverse CHD population.

OBJECTIVES: Previous cross-sectional studies have demonstrated obesity rates in children with CHD and the general paediatric population. We reviewed longitudinal data to identify factors predisposing to the development of obesity in children, hypothesising that age may be an important risk factor for body mass index growth.Study designRetrospective electronic health records were reviewed in all 5-20-year-old CHD patients seen between 2011 and 2015, and in age-, sex-, and race/ethnicity-matched controls. Subjects were stratified into aged cohorts of 5-10, 11-15, and 15-20. Annualised change in body mass index percentile (BMI%) over this period was compared using paired Student's t-test. Linear regression analysis was performed with the CHD population. RESULTS: A total of 223 CHD and 223 matched controls met the inclusion criteria for analysis. Prevalence of combined overweight/obesity did not differ significantly between the CHD cohort (24.6-25.8%) and matched controls (23.3-29.1%). Univariate analysis demonstrated a significant difference of BMI% change in the age cohort of 5-10 (CHD +4.1%/year, control +1.7%/year, p=0.04), in male sex (CHD +1.8%/year, control -0.3%/year, p=0.01), and status-post surgery (CHD 2.03%/year versus control 0.37%, p=0.02). Linear regression analysis within the CHD subgroup demonstrated that age 5-10 years (+4.80%/year, p<0.001) and status-post surgery (+3.11%/year, p=0.013) were associated with increased BMI% growth. CONCLUSIONS: Prevalence rates of overweight/obesity did not differ between children with CHD and general paediatric population over a 5-year period. Longitudinal data suggest that CHD patients in the age cohort 5-10 and status-post surgery may be at increased risk of BMI% growth relative to peers with structurally normal hearts.

Body Weights in Adults With Congenital Heart Disease and the Obesity Frequency.

Obesity may associate with greater cardiovascular risk in adults with congenital heart disease (ACHD) than in the general population. As ACHD often have exercise limitations, they may be uniquely predisposed to obesity. Nevertheless, obesity prevalence in ACHD, compared with the general population, has not been quantified in a large US cohort. Hence, we sought to determine the prevalence of obesity (30 ≤ body mass index <40) and morbid obesity (body mass index ≥40), in a large cohort of ACHD, compared with matched controls. Retrospective analysis was thus performed on all ACHD seen in an academic system in 2013. CHD severity was classified as simple, complex, or unclassified, using recently published criteria. A control group without CHD was randomly generated matching for age, gender, and race/ethnicity; 1,451 ACHD met inclusion criteria; 59.5% of ACHD were overweight to morbidly obese. Compared with controls, ACHD had similar prevalence of overweight (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89 to 1.22, p = 0.63) and obesity (OR 0.96, 95% CI 0.81 to 1.15, p = 0.69) but lower prevalence of morbid obesity (OR 0.24, 95% CI 0.16 to 0.34, p <0.001). These relationships were not attenuated by adjustment for CHD severity. In conclusion, ACHD are at equal risk as their matched peers to be overweight and obese. This is the largest study of obesity in US ACHD and the highest reported obesity prevalence in ACHD to date. As obesity is associated with significant cardiovascular risk, our findings indicate a need for improved lifestyle counseling in patients with CHD of all ages.

Manipal diabetes coronary artery severity score.

AIMS: To develop a risk score, for identifying severe and complex CAD in patients with type 2 diabetes mellitus. METHODS: In this cross sectional study, 179 patients with type 2 diabetes mellitus undergoing coronary angiogram for the evaluation of suspected coronary artery disease (CAD) were recruited at a tertiary-care hospital. Patients were divided into developmental (n=124) and validation (n=55) cohorts. Biochemical and anthropometric parameters were analysed. Predictors of severe and complex CAD (SYNTAX Score>22) were identified by multiple logistic regression analysis. RESULTS: Insulin resistance>3.4 (OR: 21.26, 95% CI: 5.71-79.09), duration of diabetes>5years (OR: 13.50, 95% CI: 3.13-58.25), total cholesterol/HDL-C ratio>5 (OR: 2.75, 95% CI: 0.66-11.55) and waist circumference>96cm (OR: 5.08, 95% CI: 1.27-20.42) were independent predictors of severe and complex CAD, and Manipal Diabetes Coronary Artery Severity Score was developed. CONCLUSIONS: The prediction of severe and complex CAD was achieved with this simple score, and thus enabling effective identification of patients beforehand, who are not likely to be suitable for angioplasty.

Severity of coronary artery disease in type 2 diabetes mellitus: Does the timing matter?

AIM: The aim of our study was to compare the angiographic changes in 53 nondiabetic patients, 54 type 2 diabetic patients of less than 5 years of duration, 41 patients with 5-10 years of diabetes, and 27 with more than 10 years of diabetic duration. METHODS: In this cross-sectional study, 175 patients, who underwent coronary angiogram for the evaluation of the coronary artery disease (CAD), were recruited. Based on the angiographic findings, syntax score, vessel score, and coronary collaterals grading were analyzed. The biochemical analysis was done by using the auto analyzer. RESULTS: A significant increase in the mean syntax score (p=0.019), vessel score (p=0.007), and coronary collateral grade (p=0.008) was observed in the patients with 5-10 years of diabetes when compared to those with less than 5 years of diabetic duration. There was no significant difference in the mean syntax score (p=0.979), vessel score (p=0.299), and collateral grade (p=0.842) between the patients with 5-10 years and more than 10 years of diabetes. The difference in the mean syntax score (p=0.791), vessel score (p=0.098), and collateral grade (p=0.661) between the nondiabetic and the patients with less than 5 years of diabetes was not significant. CONCLUSION: A significant structural change in the coronary arteries was found among the patients with 5-10 years of diabetes.

Utility of Multimodality Imaging in the Morphologic Characterization of Anomalous Aortic Origin of a Coronary Artery.

BACKGROUND: Anomalous aortic origin of a coronary artery from the wrong Sinus of Valsalva (AAOCA) is a rare congenital anomaly and is associated with sudden cardiac death. Morphologic features considered to be "high risk" are significant luminal narrowing, acute coronary angulation at its origin, intramural course, and long interarterial course. A consistent approach for characterization of these features is lacking. METHODS: A retrospective single-center review of all patients diagnosed with AAOCA using echocardiogram and computed tomography (CT)/magnetic resonance imaging (MRI) studies was performed. Twenty-nine patients were identified (25 using CT and 4 using MRI) with subsequent three-dimensional data sets. The MRI data sets lacked adequate resolution and were excluded. Twenty-five patients (median age 15.1, range 10-39.5 years, 72% male) were further analyzed using echocardiogram and CT. Morphologic assessment focused on luminal stenosis, coronary angulation, and interarterial length. Additional morphologic features focusing on cross-sectional area and degree of ellipticity were also assessed. RESULTS: Echocardiography tended to yield smaller measurements compared to CT and had poor interobserver reproducibility for measurements pertaining to the narrowest proximal and distal coronary segments. Computed tomography showed good inter-/intraobserver reproducibility for the same. Agreement between both modalities for coronary angulation at its origin was excellent. There was good agreement for measurements of interarterial length between echocardiography and CT, but echocardiography had superior reproducibility. Assessment of luminal cross-sectional area and elliptical shape by CT had excellent inter-/intraobserver reproducibility. CONCLUSION: The combination of echocardiography and CT characterizes morphologic features of anomalous origin of the coronary artery more reliably than either modality alone.

The safety of postnatal transport of newborns prenatally diagnosed with duct-dependent congenital heart disease.

OBJECTIVE: Critical congenital heart disease is increasingly recognized prenatally. Following the diagnosis, families are advised to deliver in a facility where neonatal cardiac interventions are available. We studied the safety of transport of neonates who had been prenatally diagnosed with duct-dependent congenital heart lesions. METHODS: We performed a retrospective chart review of all fetuses diagnosed with duct-dependent congenital heart disease in our fetal program between 2007 and 2011. Demographic data, dose of prostaglandin infusion, respiratory status, blood gas data, as well as complications of the transport were collected. RESULTS: Twenty-nine neonates qualified for inclusion in the study. Ten were intubated (7 electively) prior to the transport. One of these required intervention for desaturation during the transport. One of the 19 unintubated patients required emergent intubation during the transport. Thus, the overall rate of incidents was 6.9%. All 4 patients who developed apnea requiring intubation did so within 1 h of starting prostaglandin. CONCLUSIONS: Elective postnatal transport of neonates prenatally diagnosed with duct-dependent congenital heart lesions is safe. Prophylactic intubation of these infants may not be necessary. It would be advantageous to schedule the elective transport an hour after starting prostaglandin or later.

Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.

Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 µg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.

Impact of introducing consultant resident on-call in a district general hospital.

Introduction of structured competency-based training for specialty registrars and implementation of European Working Time Directives (EWTD) have affected the quality of maternity care. In York District Hospital, consultant resident on-call (CRO) without registrar cover was introduced in July 2010 to address the long-standing problem of middle-grade out-of-hours coverage. To examine the impact of introducing out-of-hours consultant resident on-call on maternity care, data from 486 deliveries including 59 CRO and 59 registrar shifts were collected retrospectively, from July 2010 to April 2011. Main outcome measures include mode of delivery, second-stage management, maternal and neonatal outcomes. Feedback from consultants, junior trainees and midwives on the impact of CRO were collated through semi-structured interviews. More normal vaginal deliveries (71.8% vs 63.0%) and fewer emergency caesarean sections (12.5% vs 20.6%) were performed in the CRO shifts compared with registrar on-call. Instrumental delivery rates in labour rooms vs theatre were higher when compared with the registrar group. Overall, good patient and staff experience was reflected during interviews. Our work shows that introduction of CRO in out-of-hours settings is acceptable among staff and is associated with fewer obstetric interventions. However, improved job descriptions may be needed in order to make the CRO post more attractive.

Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in vivo antimalarial activity.

A class of hybrid molecules consisting of 4-aminoquinoline and pyrimidine were synthesized and tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay. Eleven hybrids showed better antimalarial activity against both CQ-sensitive and CQ-resistant strains of P. falciparum in comparison to standard drug CQ. Four molecules were more potent (7-8-fold) than CQ in D6 strain, and eight molecules were found to be 5-25-fold more active against resistant strain (W2). Several compounds did not show any cytotoxicity up to a high concentration (60 µM), others exhibited mild toxicities, but the selective index for the antimalarial activity was very high for most of these hybrids. Two compounds selected for in vivo evaluation have shown excellent activity (po) in a mouse model of Plasmodium berghei without any apparent toxicity. The X-ray crystal structure of one of the compounds was also determined.