Early-stage culprit in protein misfolding diseases investigated using electrochemical parameters: New insights over peptide-membrane interactions.

The dysfunctioning of ß-cells caused by the unspecific misfolding of the human islet amyloid polypeptide (hIAPP) at the membrane results in type 2 diabetes mellitus. Here, we report for the first time, the early-stage interaction of hIAPP oligomers on the DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) lipid membrane using electrochemical parameters. Electrochemical techniques are better than other techniques to detect hIAPP at significantly lower concentrations. The surface level interactions between the peptide (hIAPP) and lipid membrane (DMPC) were investigated using atomic force microscopy (AFM), confocal microscopy (CM) and electrochemical techniques such as Tafel polarization, cyclic voltammetry (CV), differential pulse voltammetry (DPV), linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS). Inserting IAPP into the fluid domains results in breaking the lipid-to-lipid interaction, leading to restriction of membrane mobility. The SLateral values of the liposome and IAPP co-solubilized liposome indicates the cooperative insertion of IAPP. Further, a new method of immobilizing a membrane to the gold surface has been employed, resulting in an electrical contact with the buffer, preventing the direct utilization of a steady-state voltage across the bilayer. The electrochemical studies revealed that the charge transfer resistance decreased for 3-mercaptopropanoic acid modified gold (MPA-Au) electrode coated with the liposome and after the addition of IAPP, followed by an increase in the capacitance. The present study has opened up new dimensions to the understanding of peptide-membrane interactions and shows different experimental approaches for the future researchers in this domain.

Correlation Between Aortic Angulation and Outcomes of Transcatheter Aortic Valve Replacement With New-Generation Valves.

The aim of this study was to assess the correlation of aortic angulation (AA) on immediate postprocedural and long-term outcomes following transcatheter aortic valve replacement (TAVR) with new-generation valves. There is limited and conflicting data on the impact of AA on short- and long-term outcomes in patients undergoing TAVR. Available studies to date were done with first-generation valves. We assessed 179 patients who underwent TAVR with either a balloon-expandable or self-expandable valve at our institute from May 2014 to June 2017 and had multislice computed tomography scans available for AA evaluation. All included patients received a second- or third-generation valve. TAVR endpoints, device success, and adverse events were defined according to the Valve Academic Research Consortium-2 criteria. The mean AA of the study population was 49.05 ± 10.07. Patients were divided into 2 groups: AA <49 and AA ≥49, and then further subdivided by valve type. There were no difference in mean age, The Society for Thoracic Surgery (STS) score, or race distribution between the AA <49 and AA ≥49 groups. The preimplantation balloon valvuloplasty rate was higher in patients with AA ≥ 49 compared to patients with AA <49, (70% vs 55.1%, P = 0.04). There was no difference in re-hospitalization, pacemaker implantation, postprocedural aortic regurgitation or mortality between patients with AA <49 and AA ≥49 irrespective of valve type (P < 0.05). AA does not significantly affect short- or long-term outcomes in patients who undergo TAVR with new-generation balloon-expandable or self-expandable valves.

Aortic Stenosis in African Americans: Focus On Disparities in Treatment and Outcomes.

Aortic stenosis (AS) is the third most common type of cardiovascular disease after hypertension and coronary artery disease, and it carries a high mortality rate when left untreated. Risk factors include male sex, hypertension, tobacco use, advanced age, elevated LDL cholesterol, and coronary atherosclerosis. Definitive treatment for AS includes valve repair, either percutaneously or surgically; however, in aging populations corrective surgery carries increased risk. While research suggests that patients of some non-White ethnic groups, including African-Americans, are less likely than their Caucasian counterparts to have AS, these minority patients may experience may experience differences in the way they receive and accept care. This paper seeks to explicate the mechanisms of racial disparities among the African-Americans affected by aortic stenosis as they pertain to healthcare utilization, referral for valve replacement, acceptance of therapy, and overall treatment outcomes.