Nonantithrombotic Medical Options in Acute Coronary Syndromes: Old Agents and New Lines on the Horizon

Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations ranging from unstable angina and non-ST-segment elevation myocardial infarction to ST-segment myocardial infarction. Myocardial ischemia in this context occurs as a result of an abrupt decrease in coronary blood flow and resultant imbalance in the myocardial oxygen supply-demand relationship. Coronary blood flow is further compromised by other mechanisms that increase coronary vascular resistance or reduce coronary driving pressure. The goals of treatment are to decrease myocardial oxygen demand, increase coronary blood flow and oxygen supply, and limit myocardial injury. Treatments are generally divided into “disease-modifying” agents or interventions that improve hard clinical outcomes and other strategies that can reduce ischemia. In addition to traditional drugs such as beta-blockers and inhibitors of the reninangiotensin-aldosterone system, newer agents have expanded the number of molecular pathways targeted for treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are medications that have been shown to reduce myocardial ischemia through diverse mechanisms and have been tested in limited fashion in patients with ACS. Attenuating the no-reflow phenomenon and reducing the injury compounded by acute reperfusion after a period of coronary occlusion are active areas of research. Additionally, interventions aimed at ischemic pre- and post-conditioning may be useful means by which to limit myocardial infarct size. Trials are also underway to examine altered metabolic and oxygen-related pathways in ACS. This review will discuss traditional and newer anti-ischemic therapies for patients with ACS, exclusive of revascularization, anti-thrombotic agents, and the use of high-intensity statins

Constrained pre-equalization accounting for multi-path fading emulated using large RC networks: applications to wireless and photonics communications

Multi-path propagation is modelled assuming a multi-layer RC network with randomly allocated resistors and capacitors to represent the transmission medium. Due to frequency-selective attenuation, the waveforms associated with each propagation path incur path-dependent distortion. A pre-equalization procedure that takes into account the capabilities of the transmission source as well as the transmission properties of the medium is developed. The problem is cast within a Mixed Integer Linear Programming optimization framework that uses the developed nominal RC network model, with the excitation waveform customized to optimize signal fidelity from the transmitter to the receiver. The objective is to match a Gaussian pulse input accounting for frequency regions where there would be pronounced fading. Simulations are carried out with different network realizations in order to evaluate the sensitivity of the solution with respect to changes in the transmission medium mimicking the multi-path propagation. The proposed approach is of relevance where equalization techniques are difficult to implement. Applications are discussed within the context of emergent communication modalities across the EM spectrum such as light percolation as well as emergent indoor communications assuming various modulation protocols or UWB schemes as well as within the context of space division multiplexing

The Impact of COVID-19 on Cardiovascular Training Programs: Challenges, Responsibilities and Opportunities

The Covid-19 pandemic has dramatically disrupted cardiovascular disease (CVD) fellowship training. Significant reductions in cardiac volumes and simultaneous reassignment of physicians, including to Covid-centric services, have led to educational challenges in fellowship programs and disruptions to trainee experiential learning. While the initial response focused on preparedness for the anticipated surge, it is now critical to focus on the impact on training in this new era. Flexibility and innovation are needed in this highly volatile environment. Programs must respond to these changes with an eye towards providing a high quality educational experience while maintaining wellness and professional growth of fellows in training (FITs). This document seeks to chronicle the current state of CVD training and explore opportunities for response to this evolving environment

CytLEK1 Is a Regulator of Plasma Membrane Recycling through Its Interaction with SNAP-25

SNAP-25 is a component of the SNARE complex that is involved in membrane docking and fusion. Using a yeast two-hybrid screen, we identify a novel interaction between SNAP-25 and cytoplasmic Lek1 (cytLEK1), a protein previously demonstrated to associate with the microtubule network. The binding domains within each protein were defined by yeast two-hybrid, coimmunoprecipitation, and colocalization studies. Confocal analyses reveal a high degree of colocalization between the proteins. In addition, the endogenous proteins can be isolated as a complex by immunoprecipitation. Further analyses demonstrate that cytLEK1 and SNAP-25 colocalize and coprecipitate with Rab11a, myosin Vb, VAMP2, and syntaxin 4, components of the plasma membrane recycling pathway. Overexpression of the SNAP-25–binding domain of cytLEK1, and depletion of endogenous Lek1 alters transferrin trafficking, consistent with a function in vesicle recycling. Taken together, our studies indicate that cytLEK1 is a link between recycling vesicles and the microtubule network through its association with SNAP-25. This interaction may play a key role in the regulation of the recycling endosome pathway