Fibril Growth Behavior of Amyloid beta on Polymer-Based Planar Membranes: Implications for the Entanglement and Hydration of Polymers

The design of biosensors and artificial organs using biocompatible materials with a low affinity for amyloid beta peptide (A beta) would contribute to the inhibition of fibril growth causing Alzheimer's disease. We systematically studied the amyloidogenicity of A beta on various planar membranes. The planar membranes were prepared using biocompatible polymers, viz., poly(methyl methacrylate) (PMMA), polysulfone (PSf), poly(L-lactic acid) (PLLA), and polyvinylpyrrolidone (PVP). Phospholipids from biomembranes, viz., 1,2-dioleoyl-phosphatidylcholine (DOPC), 1,2-dipalmitoyl-phosphatidylcholine (DPPC), and polyethylene glycol-graft-phosphatidyl ethanolamine (PEG-PE) were used as controls. Phospholipid- and polymer-based membranes were prepared to determine the kinetics of A beta fibril formation. Rates of A beta nucleation on the PSf- and DPPC-based membranes were significantly higher than those on the other membranes. A beta accumulation, calculated by the change in frequency of a quartz crystal microbalance (QCM), followed the order: PSf > PLLA > DOPC > PMMA, PVP, DPPC, and PEG-PE. Nucleation rates exhibited a positive correlation with the corresponding accumulation (except for the DPPC-based membrane) and a negative correlation with the molecular weight of the polymers. Strong hydration along the polymer backbone and polymer-A beta entanglement might contribute to the accumulation of A beta and subsequent fibrillation

Orientation and film thickness dependencies of (100)- and (111)-oriented epitaxial Pb(Mg1/3Nb2/3)O3 films grown by metal organic chemical vapor deposition

Abstract(100)- and (111)-oriented epitaxial Pb(Mg1/3Nb2/3)O3 films with 500 and 1300 nm in thickness were grown by metal organic chemical vapor deposition. Remained strain was almost relaxed because the crystal structure of the films was almost the same as that of bulk Pb(Mg1/3Nb2/3)O3. Relative dielectric constant showed the maximum value against the temperature that depended on the measurement frequency. Maximum relative dielectric constant, εr(max.), and the temperature showing εr(max.), T(max.), decreased and increased with the frequency, respectively, are in good agreement with reported data for the bulk. εr(max.) and T(max.), respectively increased and decreased with the film thickness and (111)-oriented films showed larger value than that of the (100)-oriented one. Ferroelectricity was observed for all films up to 297 K and monotonously decreased with increasing temperature. Saturation polarization value increased with the film thickness and (111)-oriented films showed larger value than (100)-oriented ones. On the other hand, the coercive field decreased with increasing film thickness, but was almost independent with the film orientation

Acute Appendicitis in an Incarcerated Femoral Hernia: A Case of De Garengeot Hernia

Appendicitis and incarcerated hernia are frequently encountered reasons of emergency surgery for acute abdomen. The treatment in early stages of each condition is generally simple, but when these conditions are combined, the symptoms become slightly complicated, obscuring specific symptoms. Especially the lack of symptoms for appendicitis leads to delayed diagnosis, resulting in high morbidity. Amyand hernia, which contains appendix in its inguinal hernia sac, is perhaps more familiar to the general surgeons than De Garengeot hernia, which is an incarcerated femoral hernia with an appendix in its sac. We report the case of a 90-year-old female with incarcerated femoral hernia who underwent emergency hernioplasty only to reveal an inflamed appendix in its sac. The patient underwent both appendectomy and hernia repair simultaneously with synthetic mesh and was discharged on postoperative day 7 without any complications. We will also discuss the physical and radiological findings of De Garengeot hernia

N-terminal deletion of Swi3 created by the deletion of a dubious ORF YJL175W mitigates protein burden effect in S. cerevisiae

Extreme overproduction of gratuitous proteins can overload cellular protein production resources, leading to growth defects, a phenomenon known as the protein burden/cost effect. Genetic screening in the budding yeast Saccharomyces cerevisiae has isolated several dubious ORFs whose deletions mitigated the protein burden effect, but individual characterization thereof has yet to be delineated. We found that deletion of the YJL175W ORF yielded an N-terminal deletion of Swi3, a subunit of the SWI/SNF chromatin remodeling complex, and partial loss of function of Swi3. The deletion mutant showed a reduction in transcription of genes encoding highly expressed, secreted proteins and an overall reduction in translation. Mutations in the chromatin remodeling complex could thus mitigate the protein burden effect, likely by reallocating residual cellular resources used to overproduce proteins. This cellular state might also be related to cancer cells, as they frequently harbor mutations in the SWI/SNF complex

Impact of catheter ablation for atrial fibrillation on cardiac disorders in patients with coexisting heart failure

AIMS: We sought to investigate the time course of cardiac disorders after catheter ablation for atrial fibrillation (AF) in patients with coexisting heart failure (HF) during long-term follow-up. METHODS AND RESULTS: We analysed consecutive 280 patients undergoing first-time catheter ablation for AF who had coexisting HF, which was defined as prior HF hospitalization, estimated right ventricular systolic pressure ≥45 mmHg, or B-type natriuretic peptide (BNP) ≥200 pg/dL before the procedure. The primary endpoints were improvements in left ventricular ejection fraction (LVEF), E/e', BNP, left atrial dimension (LAD), and mitral regurgitation (MR) at 1 year. The secondary endpoints were serial changes of LVEF, E/e', BNP, LAD, and MR at 6 months, 1 year, and 5 years and cumulative incidence of HF hospitalization. During the mean follow-up of 5.1 ± 3.0 years, 70.7% of patients were free from recurrent AF. Among patients with LVEF < 50%, E/e' ≥ 15, BNP ≥ 200 pg/dL, LAD ≥ 40 mm, and moderate-to-severe MR, changes in those parameters from baseline to 1 year were 34.5 ± 9.9% to 43.2 ± 14.4% (P < 0.001), 19.7 ± 3.9 to 12.5 ± 6.6 (P < 0.001), 290 to 85 pg/dL (P < 0.001), and 100% to 37.8% (P < 0.001), respectively. The improvements in the cardiac disorders were maintained up to 5 years except for E/e'. In patients with LVEF < 40%, significant delayed improvement of LVEF beyond 1 year was observed (ΔLVEF = 10.5 ± 18.5, P = 0.001), but not in patients with LVEF of 40-49%. The cumulative incidence of HF hospitalization was 12.6% at 5 years. Baseline diastolic dysfunction was the only independent predictor for subsequent HF hospitalization. CONCLUSIONS: In patients undergoing AF ablation with coexisting HF, all cardiac disorders significantly improved after the procedure, which was mostly maintained during 5 year follow-up

Cardiac magnetic resonance imaging-based myocardial strain study for evaluation of cardiotoxicity in breast cancer patients treated with trastuzumab: A pilot study to evaluate the feasibility of the method

Background: Trastuzumab, used to treat breast cancer overexpressing human epidermal growth factor receptor 2, may be cardiotoxic. Cardiac magnetic resonance (CMR) imaging with myocardial strain studies has been used to evaluate subclinical biventricular myocardial changes, however, its clinical utility during chemotherapy has not been evaluated. Methods: The clinical outcomes, CMR and cardiac biomarkers of 9 women aged 62.3 ± 12.6 years with early or locally advanced breast cancer were evaluated at baseline, and at 3, 6 and 12 months after the initiation of trastuzumab. Results: None of the patients developed heart failure or elevated serum cardiac biomarkers. Global left ventricular (LV) peak systolic longitudinal and circumferential strains were significantly decreased at 6 months (longitudinal strains, –21.1 ± 1.7% [baseline] vs. –19.5 ± 1.0% [6 months], p = 0.039, and circumferential strains, –23.4 ± 1.8% [baseline] vs. –21.6 ± 2.5% [6 months], p = 0.036). These changes were analogous to those observed in the LV ejection fraction. Right ventricular (RV) free wall peak systolic circumferential strains were decreased at 6 months (–20.9% ± 2.4% [baseline] vs. –19.1% ± 2.3% [6 months], p = 0.049), whereas RV longitudinal strains and ejection fraction remained unchanged. The LV longitudinal strain was the most reproducible of the 4 peak strain parameters. Conclusions: The LV longitudinal and circumferential strains measured by CMR decreased during trastuzumab therapy, although their predictive value for later heart failure or association with RV parameters was not determined. These techniques may be a useful means of diagnosing and monitoring trastuzumab-related cardiotoxicity