Design and fabrication of Ti–Zr-Hf-Cr-Mo and Ti–Zr-Hf-Co-Cr-Mo high-entropy alloys as metallic biomaterials

Novel TiZrHfCr0.2Mo and TiZrHfCo0.07Cr0.07Mo high-entropy alloys for metallic biomaterials (bio-HEAs) were developed based on the combination of Ti–Nb–Ta–Zr–Mo alloy system and Co–Cr–Mo alloy system as commercially-used metallic biomaterials. Ti–Zr-Hf-Cr-Mo and Ti–Zr-Hf-Co-Cr-Mo bio-HEAs were designed using (a) a tree-like diagram for alloy development, (b) empirical alloy parameters for solid-solution-phase formation, and (c) thermodynamic calculations focused on solidification. The newly-developed bio-HEAs overcomes the limitation of classical metallic biomaterials by the improvement of (i) mechanical hardness and (ii) biocompatibility all together. The TiZrHfCr0.2Mo and TiZrHfCo0.07Cr0.07Mo bio-HEAs showed superior biocompatibility comparable to that of commercial-purity Ti. The superior biocompatibility, high mechanical hardness and low liquidus temperature for the material processing in TiZrHfCr0.2Mo and TiZrHfCo0.07Cr0.07Mo bio-HEAs compared with the Ti–Nb–Ta–Zr–Mo bio-HEAs gave the authenticity of the application of bio-HEAs for orthopedic implants with multiple functions.Nagase T., Iijima Y., Matsugaki A., et al. Design and fabrication of Ti–Zr-Hf-Cr-Mo and Ti–Zr-Hf-Co-Cr-Mo high-entropy alloys as metallic biomaterials. Materials Science and Engineering C, 107, 110322. https://doi.org/10.1016/j.msec.2019.110322

Design and development of Ti–Zr–Hf–Nb–Ta–Mo high-entropy alloys for metallic biomaterials

Applying empirical alloy parameters (including Mo equivalent), the predicted ground state diagram, and thermodynamic calculations, noble nonequiatomic Ti–Zr–Hf–Nb–Ta–Mo high-entropy alloys for metallic biomaterials (BioHEAs) were designed and newly developed. It is found that the Moeq and valence electron concentration (VEC) parameters are useful for alloy design involving BCC structure formation in bio medium-entropy alloys and BioHEAs. Finally, we find a Ti28.33Zr28.33Hf28.33Nb6.74Ta6.74Mo1.55 (at.%) BioHEA that exhibits biocompatibility comparable to that of CP–Ti, higher mechanical strength than CP–Ti, and an appreciable room-temperature tensile ductility. The current findings pave the way for new Ti–Zr–Hf–Nb–Ta–Mo BioHEAs development and are applicable for another BioHEA alloys system.Iijima Y., Nagase T., Matsugaki A., et al. Design and development of Ti–Zr–Hf–Nb–Ta–Mo high-entropy alloys for metallic biomaterials. Materials and Design, 202, 109548. https://doi.org/10.1016/j.matdes.2021.109548

Anti-tachycardia pacing degenerated fast ventricular tachycardia into undetectable life-threatening tachyarrhythmia in a patient with non-ischemic dilated cardiomyopathy

SummaryA 45-year-old man with dilated cardiomyopathy was admitted to our hospital due to congestive heart failure (CHF). Despite the optimal medical treatment, his condition had not improved because of severe left ventricular dysfunction. Because he experienced non-sustained ventricular tachycardia (VT), a biventricular implantable cardioverter-defibrillator (Bi-V ICD) was implanted for reduction of dyssynchrony and primary prevention of lethal tachyarrhythmia. After discharge, he developed CHF and was transported to our hospital by ambulance. In the ambulance, monomorphic sustained VT with 200bpm suddenly occurred. The ICD detected it as fast VT and anti-tachycardia pacing (ATP) was delivered. After the ATP therapy, RR intervals of VT became irregular and prolonged. Ventricular fibrillation-like electrical activity was recorded by a far-field electrogram from the defibrillator, but the tachycardia cycle length exceeded 400ms which is under the tachycardia detection rate. The device failed to deliver a shock and the patient had to be rescued with an external shock. This is a rare case of fast VT that degenerated into undetectable life-threatening tachyarrhythmia by ATP

Cohort Analysis of Gender Role Attitudes: A Conservative Shift among the Younger Generation?

この論文は、永瀬圭・太郎丸博, 2014, 「性役割意識のコーホート分析 --若者は保守化しているか?--」『ソシオロジ』58(3): 19-33の英訳である。This paper is an English translation of the following paper: Nagase, Kei and Hiroshi Tarohmaru, 2014, "Cohort Analysis of Gender Role Attitudes: A Conservative Shift among the Younger Generation?, " Soshioroji, 58(3): 19-33

Efficacy and safety of third- and fourth-line targeted therapy in japanese patients with metastatic renal cell carcinoma: A retrospective analysis

Introduction: There is limited data on the efficacy of sequential targeted therapy for metastatic renal cell carcinoma (mRCC) beyond the second line, especially for Asian patients. We evaluated the efficacy and side effects of targeted therapy beyond the second line. Materials and Methods: We retrospectively reviewed 69 patients who were administered targeted therapy for mRCC at our institution between 2008 and 2016. Sunitinib, pazopanib, sorafenib, axitinib, everolimus, and temsirolimus were available in Japan in 2016, and treatment had been conducted with those six agents. Twenty-four patients underwent therapy beyond the second line. The progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. In addition, a survey on patients' attitudes toward cancer treatment was conducted. Twenty-five of the 69 patients responded to the question with their opinions on the continuation of treatment after standard therapy failure. Results: The median PFS was 7.6 and 2.5 months for third- and fourth-line therapy. The median OS calculated from the initiation of third-line therapy was 14.2 months. The rates of serious toxicities with third- and fourth-line regimens were not markedly increased compared with first- and second-line therapies. Forty percent of patients hoped to continue treatment after exhausting standard care. Conclusions: Our retrospective study indicates the efficacy and safety of third- and fourth-line targeted therapies. In addition to the efficacy, a patient can also influence treatment continuation

LAT1-Targeting Thermoresponsive Liposomes for Effective Cellular Uptake by Cancer Cells

L-type amino acid transporter 1 (LAT1) is a transporter that is more highly expressed in cancer cells compared with normal cells. In the present study, liposomes, composed of egg phosphatidylcholine (EPC) and dioleoyl phosphatidylethanolamine, were modified with LAT1-targeting thermoresponsive polymer, l-tyrosine-conjugated poly­(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P­(NIPAAm-co-DMAAm)). The cellular uptake of the prepared LAT1-targeting liposomes was evaluated using HeLa cells as a cancer cell model. At temperatures above the polymer’s lower critical solution temperature, uptake of the liposomes into cells was observed because the polymer at the liposome surface became hydrophobic and interacted with the cell membrane. Flow cytometry analysis suggested that l-tyrosine-P­(NIPAAm-co-DMAAm)-liposomes exhibited markedly increased cellular uptake by HeLa cells compared with that of liposomes not modified with l-tyrosine. This result indicated that cellular uptake of liposomes can be enhanced by the affinity between l-tyrosine and the LAT1 of HeLa cells. The developed functional liposomes, which exhibit both thermoresponsive and LAT1-targeting properties, would be appropriate for temperature-modulated drug delivery and imaging with good targeting ability