Chiral auxiliaries and substrate-directable reactions in asymmetric synthesis

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Role of Lipids in Spheroidal High Density Lipoproteins

We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly

Impact of Chronic Obstructive Pulmonary Disease on Outcomes After Transcatheter Mitral Valve Repair

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased mortality and morbidity after cardiac valve surgeries and coronary angioplasty. However, the association of COPD with in-hospital outcomes after transcatheter mitral valve repair (TMVr) has not been established. Methods: Elective TMVr procedures among adults were identified using the National Readmissions Database (NRD) from January 2012 to August 2015. ICD-9 codes were used to identify patients with and without COPD. Multivariate linear and logistic regressions were used to calculate odds ratios for primary and secondary outcomes after adjusting for confounders. Primary outcomes were all-cause in-hospital mortality and associated in-hospital complications after TMVr in COPD vs non-COPD patients. Results: Of the 1,741 patients who underwent TMVr procedures during the study period, 256 (14.7%) had documented COPD. Patients with COPD were more likely to have a high burden of comorbidities (CCI 2 vs 1, p\u3c0.001), including congestive heart failure, long-term oxygen dependence, dyslipidemia, obesity, smoking, and prior coronary artery disease (p\u3c0.05 for all). There was no significant difference in all-cause in-hospital mortality (aOR 0.76, p=0.583), major bleeding (aOR 0.86, p=0.367), pacemaker placement (aOR 0.93, p=0.771), acute kidney injury (aOR 0.90, p=0.642), home discharge (aOR 1.15, p=0.367), and mean length of hospitalization (aOR -0.35, p=0.550). Patients with COPD were more likely to be discharged to a skilled nursing facility (aOR 1.80, 95% CI 1.24-2.73, p=0.007) compared to non-COPD patients. Conclusion: COPD did not impact in-hospital mortality or post-operative outcomes after TMVr. However, further studies are needed to evaluate the effect of COPD on long-term outcomes after TMVr

Impact of Peripheral Vascular Disease After Transcatheter Mitral Valve Repair: Insights From the National Inpatient Sample

Background: Peripheral vascular disease (PVD) is an independent predictor of poor outcomes after cardiovascular interventions and surgeries. Association of PVD with in-hospital outcomes after transcatheter mitral valve repair (TMVr) has not been studied. Methods: Adults who underwent TMVr procedures from January 2011 to September 2015 were identified using the National Inpatient Sample. ICD-9 codes were used to differentiate PVD versus non-PVD patients. Multivariate linear and logistic regressions were used to calculate odds ratios for primary and secondary outcomes while adjusting for confounders. Results: A total of 5,093 patients underwent TMVr procedure, of which 618 (12.1%) had documented PVD. Patients with PVD were more likely older, male and smokers with comorbidities including hypertension, diabetes, dyslipidemia, previous myocardial infarction, previous coronary bypass surgery, chronic pulmonary disease, liver disease, renal failure, hemodialysis status and coagulopathy (p\u3c0.05 for all). Patients with PVD had lower odds of all-cause in-hospital mortality (aOR 0.35, p=0.031) and postoperative infection (aOR 0.31, p=0.009) compared to non-PVD patients. Higher odds of pacemaker requirement (aOR 2.52, p\u3c0.001), pericardial complications (aOR 3.23, p\u3c0.001), perioperative stroke (aOR 22.36, p\u3c0.001), mechanical ventilation (aOR 1.51, p=0.011) and venous thromboembolism (VTE) (aOR 4.28, p\u3c0.001) were noted in PVD patients. PVD patients demonstrated comparable length of hospital stay but higher hospital charges. Conclusion: Presence of PVD marginally lowered the odds of mortality, iatrogenic cardiac complications, and infection after TMVr. However, these patients are at increased risk of pacemaker requirement, stroke, pericardial complications, mechanical ventilation and VTE