A Novel Serum-Free Monolayer Culture for Orderly Hematopoietic Differentiation of Human Pluripotent Cells via Mesodermal Progenitors

Elucidating the in vitro differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells is important for understanding both normal and pathological hematopoietic development in vivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfully trace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monolayer culture that can trace the in vivo hematopoietic pathway from ES/iPS cells to functional definitive blood cells via mesodermal progenitors. Stepwise tuning of exogenous cytokine cocktails induced the hematopoietic mesodermal progenitors via primitive streak cells. These progenitors were then differentiated into various cell lineages depending on the hematopoietic cytokines present. Moreover, single cell deposition assay revealed that common bipotential hemoangiogenic progenitors were induced in our culture. Our system provides a new, robust, and simple method for investigating the mechanisms of mesodermal and hematopoietic differentiation

Anterior relapse or posterior drift after intraoral vertical ramus osteotomy

This study aimed to evaluate the factors contributing to postoperative anterior relapse or posterior drift of the distal segment after intraoral vertical ramus osteotomy. A retrospective cohort study was conducted which included 31 patients who underwent setback surgery for mandibular prognathism by the intraoral vertical ramus osteotomy technique. Uni- and multivariate analyses were performed to determine the association of potential explanatory variables (sex, age, magnitude of setback, differences in setback magnitude between sides (right/left), duration of splint use, Angle’s classification of malocclusion, mandibular angle, and tightness of occlusion of the molars) with positional changes in the distal segment. The setback magnitude was only significant factor affecting (P = 0.015) for posterior drift, with significant posterior in setback magnitudes of less than 7.25 mm. Posterior drift after intraoral vertical ramus osteotomy is less likely if setback magnitude exceeds 7.25 mm. For setbacks less than 7.25 mm, posterior drift should either be carefully corrected postoperatively, or an alternative surgical technique should be used. The setback magnitude showed a significant association with the risk of posterior drift following intraoral vertical ramus osteotomy, and the determined cut-off value may serve as a predictor for postoperative outcomes

Effect of Iron Content on Hot Tearing of High-Strength Al-Mg-Si Alloy

The effect of iron content on hot tearing of the high-strength Al-Mg-Si alloy was systematically investigated. The alloy with higher content of iron resulted in the severe occurrence of hot tearing during direct chill (DC) casting. Mechanical properties of this alloy in which iron content was changed were investigated during solidification using an electromagnetic induction heating tensile machine. Tensile strength and elongation were discussed in relation with solidification progress of which sequence of crystallization, crystallization temperature of formed phases and their crystallized amount were calculated by a thermodynamic calculation software Thermo-Calc. In order to confirm the calculation results of solidification path, a quenching test also was carried out. Furthermore, by comparing the fracture surfaces of the tensile testing sample and DC billet, the temperature range of crack initiation of the alloy was examined. Comparing the temperature range of crack initiation with the crystallization phase and its crystallization order, iron content influenced hot tearing significantly owing to the crystallization behavior of (AlFeMn) in high-strength Al-Mg-Si alloy. [doi:10.2320/matertrans.47.2821

Mechanical Properties of High Strength Al-Mg-Si Alloy during Solidification

Mechanical properties of high strength Al-Mg-Si alloy during solidification have been investigated. Tensile strength and ductility have been measured by using an electromagnetic induction heating tensile machine. The relation between solid fraction and temperature was calculated by the Gulliver-Scheil model applied with the thermodynamic data-base Thermo-Calc for multi-component system, and its validity was confirmed, comparing with the experiment. Zero Strength Temperature (ZST) and Zero Ductility Temperature (ZDT) were evaluated and correlated with the corresponding solid fraction. Furthermore, the capability of the high temperature tensile test to apply to the break-out of direct chill (DC) casting was examined, comparing the breaking section of the tensile test sample with that of DC billet. Main conclusions are as follows

A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension

<p><b>Purpose:</b> Patients with essential hypertension who are receiving treatment with an angiotensin II receptor blocker and a calcium channel blocker often develop inadequate blood pressure (BP) control and require the addition of a diuretic. This study aimed to evaluate the long-term safety and efficacy of a triple combination therapy with 20 mg azilsartan (AZL), 5 mg amlodipine (AML) and 12.5 mg hydrochlorothiazide (HCTZ).</p> <p><b>Materials and methods:</b> The phase III, open-label, multicenter study (NCT02277691) comprised a 4-week run-in period and 52-week treatment period. Patients with inadequate BP control despite AZL/AML therapy (<i>n</i> = 341) received 4 weeks’ treatment with AZL/AML (combination tablet) + HCTZ (tablet) and 4 weeks’ treatment with AZL/AML/HCTZ (combination tablet) in a crossover manner, followed by AZL/AML/HCTZ (combination tablet) from Week 8 of the treatment period up to Week 52. The primary and secondary endpoints were long-term safety and BP (office and home), respectively.</p> <p><b>Results:</b> Most adverse events (AEs) were mild or moderate in intensity, and no deaths or treatment-related serious AEs were reported. The triple therapy provided consistent BP-lowering effects in both office and home measurements.</p> <p><b>Conclusions:</b> The triple combination therapy with AZL/AML/HCTZ was well tolerated and effective for 52 weeks in Japanese patients with essential hypertension.</p

Molecular characterization of blaKHM-1 encoding plasmid in an Enterobacter hormaechei subsp. hoffmannii isolate from blood culture.

KHM-1 was first reported in 1997 in Japan as a novel metallo-β-lactamase mediated by Citrobacter freundii carrying pKHM-1 plasmid. There have been few reports in the clinical field since then. A blaKHM-1-positive Enterobacter hormaechei subsp. hoffmannii in E. cloacae complex, isolate OIPH-N069 was isolated from an inpatient blood culture in 2016. The isolate was characterized by whole-genome sequencing, comparative analysis of the blaKHM-1 encoding plasmid, antimicrobial susceptibility tests, and bacterial conjugation. OIPH-N069 was classified into ST78 of E. cloacae complex, and was multidrug resistant because of the presence of antimicrobial resistance genes in addition to blaKHM-1 on its chromosome and plasmids. blaKHM-1 was located on 136,816 bp of the IncA/C2 plasmid pN069-1, which could be transferred to different bacterial species. The backbone structure, genetic arrangement of the class 1 integron cassette, and the blaKHM-1 gene located downstream of the IncA/C2 antibiotic resistance island, ARI-A, in pN069-1 and pKHM-1 were identical. Horizontal gene transfer of the blaCTX-M-2-ISEcp1 resistance gene module only occurred with pN069-1. The study findings indicate not only the structural conservation of blaKHM-1 encoding plasmids over time and across species, but also the risk of the spread of blaKHM-1 encoding plasmids to other bacterial species and the accumulation of additional resistance genes