Acute coronary syndromes (ACS) frequently cause considerable morbidity and mortality with a high risk of further events within the following year, despite the use of percutaneous coronary ...intervention (PCI). Numerous studies have described the concept of acute, partial or complete thrombotic occlusion of the coronary artery, which occurs at the site of a friable atherosclerotic plaque with a lipidrich necrotic core and a ruptured overlying thin fibrous cap ("culprit lesion"). Moreover, this process appears independent of the severity of the underlying stenosis. Most of our knowledge about the morphological characteristics of culprit lesions has been obtained from necropsy studies of lesions at the extreme end of the ACS spectrum. The development of intravascular ultrasound (IVUS) with virtual histology (VH), using spectral analysis of the radiofrequency ultrasound backscatter signals to identify the components of atherosclerotic plaque, has allowed in-vivo delineation of the relative contributions of necrotic core and fibrous atheroma in unstable lesions. This evidence suggests that there may be variations in the morphology of plaques that rupture and promote thrombosis in ACS, rather than the traditionally accepted view that a common pathological mechanism is at play. This imaging modality, therefore, provides great potential for invivo information about the culprit lesion. In this review article, we explore the background and potential application of virtual histology to improve the invasive treatment of ACS patients.
Elevated preprocedural systemic markers of inflammation, including white blood cell count, have been associated with adverse clinical outcomes after percutaneous coronary intervention. The ...relationship between preoperative white blood cell count and clinical outcomes after coronary artery bypass grafting is less clear despite increasing evidence that neutrophils participate in reperfusion injury. We sought to determine the relationship between preoperative white blood cell count and in hospital major morbidity and 1-year survival after coronary artery bypass grafting.
We prospectively studied 3,024 consecutive isolated coronary artery bypass graft procedures. Preoperative white blood cell count was determined by automated counter, perioperative cardiac enzyme release by the creatine kinase–myocardial band isoenzyme, and all-cause mortality over the first postoperative year taken from a national death registry. Multivariate logistic regression and Cox proportional hazards analyses were performed.
Preoperative white blood cell count offered as a continuous variable and as five predetermined groups was independently associated with cardiac enzyme release three or more times the upper limit of the reference range (adjusted odds ratio = 1.5 per 10 × 10
9/L increase, 95% confidence interval: 1.2 to 2.0,
p = 0.002) and higher 1-year mortality (adjusted hazard ratio = 1.6 per 10 × 10
9/L increase, 95% confidence interval: 1.2 to 2.1,
p < 0.001).
Higher preoperative white blood cell count is independently associated with higher perioperative myonecrosis and 1-year mortality after coronary artery bypass grafting.
Although antimicrobial resistance is an increasingly significant public health concern, there have only been two new classes of antibiotics approved for human use since the 1960s. Understanding the ...mechanisms of action of antibiotics is critical for novel antibiotic discovery, but novel approaches are needed that do not exclusively rely on experiments. Molecular dynamics simulation is a computational tool that uses simple models of the atoms in a system to discover nanoscale insights into the dynamic relationship between mechanism and biological function. Such insights can lay the framework for elucidating the mechanism of action and optimizing antibiotic templates. Antimicrobial peptides represent a promising solution to escalating antimicrobial resistance, given their lesser tendency to induce resistance than that of small-molecule antibiotics. Simulations of these agents have already revealed how they interact with bacterial membranes and the underlying physiochemical features directing their structure and function. In this minireview, we discuss how traditional molecular dynamics simulation works and its role and potential for the development of new antibiotic candidates with an emphasis on antimicrobial peptides.
Background: Percutaneous coronary intervention (PCI) is increasingly performed from the radial arterial (RA) access site. Few studies have examined the interaction between a default radial approach, ...lesion complexity, and angiographic outcome. This study investigates lesion complexity, arterial access route, and angiographic outcome in routine clinical practice by default radial operators.
Methods: All cases of PCI over a 12‐month period (Jan 2005 to Jan 2006) at our regional cardiac center were prospectively entered into a database detailing arterial access route, target vessel and lesion characteristics, and lesion‐specific angiographic outcome. Angiographic success was defined as residual stenosis <50% for balloon angioplasty alone or <20% for a stented lesion in the presence of TIMI 3 flow in the target vessel. All procedures carried out by default radial operators were selected for further retrospective analysis. Reasons for not completing a case via the radial route were recorded. Radial and femoral cases by default radial operators were evaluated on grounds of lesion complexity and angiographic outcome for each treated lesion.
Results: RA was the intended route in 91.5% of 1,324 procedures (91.5% of 2,239 lesions), and the final route in 90.1% of procedures (90.2% of lesions). There were 19 crossover procedures (30 lesions), all from radial to femoral access (FA). Crossovers were due to failed radial artery cannulation or sheath placement (9 procedures), inability to advance the guide catheter into the aortic root (7 procedures), and other guide catheter handling or support issues (3 procedures). Counting crossovers as failures, angiographic success rate was 96% among lesions for which RA was the primary intention. Complexity of cases was high (80.1% of RA lesions ACC/AHA type B2 or C).
Conclusions: A default radial approach is compatible with successful treatment of a wide range of coronary lesions, with a low incidence of crossover to femoral access. When the radial approach fails, it is usually due to access problems rather than issues of guide catheter handling and support.
Offloading computation from smartphones to remote cloud resources has recently been rediscovered as a technique to enhance the performance of smartphone applications, while reducing the energy usage.
...In this paper we present the first practical implementation of this idea for Android: the Cuckoo framework, which simplifies the development of smartphone applications that benefit from computation offloading and provides a dynamic runtime system, that can, at runtime, decide whether a part of an application will be executed locally or remotely. We evaluate the framework using two real life applications.
We report the first racemic and stereoselective synthesis of cis- and trans-N-alkylaziridines viaN-chloroamines; using this methodology an N-3,4,5-trimethoxybenzylaziridine was synthesised and ...efficiently cleaved, affording the corresponding NH aziridine in high yield.
The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic ...knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.
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