Elevated Levels of VE-Cadherin-Positive Endothelial Microparticles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

ObjectivesThe purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM).BackgroundEndothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis.MethodsWe characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM.ResultsWe demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001).ConclusionsThe CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at −20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size

Short lingual osteotomy without fixation: a new strategy for mandibular osteotomy known as “physiological positioning”

We describe the strategy of physiological positioning, which we regard as a new alternative treatment to conventional orthognathic operations, and treated 18 patients with skeletal mandibular prognathism using it. The positions of SNB, FMA, and Me were measured postoperatively to assess skeletal stability, changes in the angle and perpendicular length of the upper and lower central incisors were measured to assess dental stability, and we confirmed that both skeletal and dental stability were excellent. The width to which the jaw could be opened recovered early, and we saw only one case of disorder of the temporomandibular joint. Short lingual osteotomy with physiological positioning is an effective new approach to the treatment of deformities of the mandible

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A mutant gene for albino body color is widespread in natural populations of tanuki (Japanese raccoon dog)

中央アルプスと伊勢で発見された白いタヌキの体色変異の原因を解明 --アルビノ遺伝子の哺乳類における広域拡散の初事例--. 京都大学プレスリリース. 2021-03-08.Albino mutants (white coat and red eyes) of tanuki (Nyctereutes procyonoides viverrinus) have been repeatedly found in the Central Alps area of Japan. We recently reported that an albino tanuki from Iida, a city in this area, lacks the third exon of the TYR gene encoding tyrosinase, which is essential for melanin synthesis. The absence of this exon was due to the chromosomal deletion of a complex structure. In the present study, we analyzed TYR of another albino tanuki that was found in Matsusaka, a city located outside the mountainous area. In this animal, the third exon was also lost, and the loss was due to a deletion in which the structure was identical to that of the Iida mutant. Our results indicate, in consideration of the complex structure of the deletion, that the two albino animals inherited a single deletion that arose in their common ancestor. Iida and Matsusaka are approximately 170 km apart. This is, to our knowledge, the first report of an albino mutant gene that is widely distributed in mammalian natural populations. As the origin of this mutation is not known, the distance covered by the mutant gene remains unclear. If we assume that the mutation occurred halfway between Iida and Matsusaka, we can predict the migration distance to be approximately 85 km; however, if the mutation occurred at any other place, a longer distance would be predicted. Natural selection against albino tanuki may be relaxed because of a recent increase in food resources and refuge in urban areas

Evaluation of Skin Friction Drag Reduction in the Turbulent Boundary Layer Using Riblets

A unique approach to evaluate the reduction of skin friction drag by riblets was applied to boundary layer profiles measured in wind tunnel experiments. The proposed approach emphasized the turbulent scales based on hot-wire anemometry data obtained at a sampling frequency of 20 kHz in the turbulent boundary layer to evaluate the skin friction drag reduction. Three-dimensional riblet surfaces were fabricated using aviation paint and were applied to a flat-plate model surface. The turbulent statistics, such as the turbulent scales and intensities, in the boundary layer were identified based on the freestream velocity data obtained from the hot-wire anemometry. Those turbulent statistics obtained for the riblet surface were compared to those obtained for a smooth flat plate without riblets. Results indicated that the riblet surface increased the integral scales and decreased the turbulence intensity, which indicated that the turbulent structure became favorable for reducing skin friction drag. The proposed method showed that the current three-dimensional riblet surface reduced skin friction drag by about 2.8% at a chord length of 67% downstream of the model&rsquo;s leading edge and at a freestream velocity of 41.7 m/s (Mach 0.12). This result is consistent with that obtained by the momentum integration method based on the pitot-rake measurement, which provided a reference dataset of the boundary layer profile

Time-Series-Data Interpolation Applied to Boundary-Layer Profiles Measured on Different Flights

Turbulent boundary-layer profiles on an aircraft surface were measured during flight by pitot rakes in an experiment at subsonic speeds. Because separate flights have different flight sequences in terms of time, it is not easy to compare boundary-layer profiles measured on different flights with the corresponding premised conditions directly. Using one flight as a reference, this paper proposes a method to find the closest flight condition for each time instance from data from other flights by calculating a residual norm in combinations of flight variables. The results show that the proposed method successfully finds the best matches of the time instances from the second flight with those of the first flight. In addition, applying the interpolation method using response surface methodology further improves the accuracy of evaluation in the flight range of Mach 0.4 to Mach 0.8. The total uncertainty level of the proposed interpolation method was found to be 5.7%. Although this level of uncertainty is expected to be reduced, the effectiveness of the proposed interpolation method was presented in conjunction with an evaluation of its applicability to determine the riblet effect in reducing skin-friction drag qualitatively