Direct Pulp Capping Effect with Experimentally Developed Adhesive Resin Systems Containing Reparative Dentin Promoting Agents on Rat Pulp -Mixed Amounts of Additives and Their Effect on Wound Healing-

This study examined the wound healing process of exposed rat pulp when treated with experimental adhesive resin systems. The experimental direct pulp capping adhesive resin systems were composed of primer-I, primer-II and an experimental bonding agent. Primer-I was Clearfil SE Bond (CSE) primer containing 1.0 or 5.0wt% CaCl2, and primer-II was CSE primer containing 0.1, 1.0 or 5.0wt% compound of equal mole of pA and pB with synthetic peptides derived from dentin-matrix-protein 1 (DMP1). Primer-I containing 1.0wt% and 5.0wt% CaCl2 were assigned to the experimental groups 1 to 3, and 4 to 6, respectively. Primer-II containing 0.1, 1.0 or 5.0wt% compound of pA and pB were assigned to the experimental groups 1 and 4, 2 and 5, and 3 and 6, respectively. In all experimental groups, CSE bond containing 10wt% hydroxyapatite powder was used as the experimental bonding agent. The positive control teeth were capped with calcium hydroxide preparation (Dycal), and the negative control teeth were capped with CSE. The specimens were alternately stained with Mayer's H&E and the enhanced polymer one-step staining method. Experimental groups 1, 4, 5 and 6 showed a higher level of reparative dentin formation compared to the negative control 14 days postoperatively. At 28 days postoperatively, all experimental groups showed the formation of extensive reparative dentin, and experimental groups 4, 5 and 6 demonstrated similar dentin bridge formation as that of the positive control. How quickly reparative dentin formation occurs might depend on the concentration of CaCl2 and pA and pB in the experimental primer

Simulation study of helium bubble coalescence in tungsten at various temperatures relevant to fusion conditions

Molecular dynamics (MD) methods are used to study nanosized helium (He) bubble coalescence process in tungsten (W) at various temperatures relevant to fusion conditions, on an atomistic scale. Bubble coalescence in W is observed at a higher temperature and He/V ratio, while the calculated internal bubble pressure due to virial stress increases with the increase in the He/V ratio; bubble coalescence is significantly dependent on the bubble distance. In these MD simulations, coalescence occurs, only when the surface distance between the two bubbles is equal to 1a0, where a0 denotes the lattice constant and is approximately 0.317 nm at 2100 K. On the other hand, a bubble diameter between 1a0 and 3a0 may have relatively limited effect on the coalescence, although larger-sized bubbles may have higher migration energy. Local stress profile calculated indicates that initial bubbles can interact with each other, which may enhance the He atoms diffusion between bubbles and their coalescence. Physical contact at the initial stage of coalescence may occur between two nearby bubbles accompanied by W lattice distortion because of the limited displacement of W atoms near the bubbles and rapid migration of He atoms within the two bubbles. These results are beneficial for understanding the evolution of He bubbles in bulk W

A novel insertion pathway of mitochondrial outer membrane proteins with multiple transmembrane segments

The central channel Tom40 of the preprotein translocase of outer membrane (TOM) complex is thought to be responsible for the import of virtually all preproteins synthesized outside the mitochondria. In this study, we analyze the topogenesis of the peripheral benzodiazepine receptor (PBR), which integrates into the mitochondrial outer membrane (MOM) through five hydrophobic transmembrane segments (TMSs) and functions in cholesterol import into the inner membrane. Analyses of in vitro and in vivo import into TOM component–depleted mitochondria reveal that PBR import (1) depends on the import receptor Tom70 but requires neither the Tom20 and Tom22 import receptors nor the import channel Tom40, (2) shares the post-Tom70 pathway with the C-tail–anchored proteins, and (3) requires factors of the mitochondrial intermembrane space. Furthermore, membrane integration of mitofusins and mitochondrial ubiquitin ligase, the MOM proteins with two and four TMSs, respectively, proceeds through the same initial pathway. These findings reveal a previously unidentified pathway of the membrane integration of MOM proteins with multiple TMSs

Normalization of Pulmonary Hypertension by the Use of Left Ventricular Assist Device in Patients with End-stage Heart Failure: A Possible Contribution to Donor Pool Expansion in Lung Transplantation

SummaryHeart transplantation alone has been recognized to be contraindicated when pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) are irreversible, irrespective of any medical intervention by the use of inotropic agents or pulmonary vasodilators, because such patients are at an increased risk of post-transplantation right ventricular failure and mortality. Therefore, end-stage heart failure patients with concomitant fixed PH and irreversibly high PVR are considered to be heart–lung transplant candidates. Recently, left ventricular assist device (LVAD) therapy has been reported to normalize PVR through persistent unloading of the left ventricle, even in patients with medically refractory PH. Therefore, LVAD therapy could make such patients suitable for “heart-only” transplants, which contributes to appropriate donor lung allocation for lung-only candidates. We review the literature regarding LVAD use for secondary PH and present a case with end-stage heart failure that could avoid a heart–lung transplant owing to LVAD therapy

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)

Isolation of C11 Cyclopentenones from Two Didemnid Species, Lissoclinum sp. and Diplosoma sp.

A series of new C11 cyclopentenones 1–7 was isolated, together with four known metabolites 9/10, 12 and 13, from the extract of the didemnid ascidian Lissoclinum sp. The other didemnid ascidian Diplosoma sp. contained didemnenones 1, 2 and 5, and five known metabolites 8–12. The structures of 1–7 were elucidated by spectroscopic analyses. Cytotoxicity of the isolated compounds was evaluated against three human cancer cell lines (HCT116, A431 and A549)