An optical transition-edge sensor with high energy resolution

Optical transition-edge sensors have shown energy resolution for resolving the number of incident photons at the telecommunication wavelength. Higher energy resolution is required for biological imaging and microscope spectroscopy. In this paper, we report on a Au/Ti (10/20 nm) bilayer TES that showed high energy resolution. This was achieved by lowering the critical temperature Tc to 115 mK and the resultant energy resolution was 67 meV full width at half maximum (FWHM) at 0.8 eV. When Tc was lowered to 115 mK, the theoretical resolution would scaled up to 30 meV FWHM, considering that the typical energy resolution of optical TESs is 150 meV and Tc is 300 mK. To investigate the gap between the theoretical expectation (30 meV) and the measured value (67 meV), we measured its complex impedance and current noise. We found excess Johnson noise in the TES and an excess Johnson term M was 1.5 at a bias point where the resistance was 10% of normal resistance. For reference, the TES was compared with a TES showing typical energy resolution (156 meV FWHM). We will discuss what improved the energy resolution and what might have been the limiting factor on it

Effect of LCZ696, a dual angiotensin receptor neprilysin inhibitor, on isoproterenol-induced cardiac hypertrophy, fibrosis, and hemodynamic change in rats

Background: Recent clinical studies have shown that treatment with LCZ696, a complex containing the angiotensin receptor blocker valsartan and neprilysin inhibitor sacubitril, improves the prognosis of heart failure patients with a reduced ejection fraction. This study evaluated whether LCZ696 affects left ventricular hypertrophy, fibrosis, and hemodynamics in isoproterenol (ISO)-treated rats compared with valsartan alone. Methods: Male Wistar rats received subcutaneous saline (n = 10), subcutaneous ISO (2.4 mg/kg/day; n = 10), subcutaneous ISO + oral LCZ696 (60 mg/kg/day; n = 20) (ISO-LCZ), or subcutaneous ISO + oral valsartan (30 mg/kg/day; n = 20) (ISO-VAL) for 7 days. Results: LCZ696 and valsartan did not significantly reduce the increased heart weight/body weight ratio in rats treated with ISO. Echocardiography showed that the deceleration time shortened by ISO was restored by LCZ696 but not valsartan alone (p = 0.01 vs. the ISO group). Histological analysis showed that cardiac interstitial fibrosis increased by ISO was decreased significantly by LCZ696 but not valsartan alone (control: 0.10 ± 0.14%; ISO: 0.41 ± 0.32%; ISO-LCZ: 0.19 ± 0.23% [p < 0.01 vs. the ISO group]; ISO-VAL: 0.34 ± 0.23% [p = 0.34 vs. the ISO group]). Quantitative polymerase chain reaction showed that mRNA expression of Tgfb1, Col1a1, Ccl2, and Anp increased by ISO was significantly attenuated by LCZ696 but not valsartan alone (p < 0.05 vs. the ISO group). Conclusions: LCZ696 improves cardiac fibrosis, but not hypertrophy, caused by continuous exposure to ISO in rats

Electrocardiographic Parameters and Fatal Arrhythmic Events in Patients With Brugada Syndrome

Objectives This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). Background Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear. Methods Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 +/- 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/ genetic and electrocardiographic parameters were compared with VF/SCD events. Results On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration >= 120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/ absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01). Conclusions The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high-and low-risk BrS patients

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet

Background Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Methods Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. Results After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. Conclusions Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression

通気デバイスを用いて湿度調整した空気の送風が圧迫性皮膚傷害に及ぼす影響

　正常な皮膚は外界からの刺激に対するバリア機能を有するが，「浸軟」や「ドライスキン」などの脆弱な状態では外界からの刺激に対してダメージを受けやすい。本研究では，通気デバイスを用いて圧迫中の皮膚に対して湿度を調整した空気を送風することにより，圧迫性皮膚傷害の発生に対する影響を検討することとした。　磁石でラット皮膚に圧迫を行い， 1 匹あたり4 箇所の圧迫性皮膚傷害を8 匹（32 創）作成した。32 創を乾燥群（湿度約25％，10 創），中間群（湿度40 〜 50％，12 創），高湿群（湿度70％以上，10 創）の3 群に分け，発赤面積・重症度・潰瘍発生率の測定を行った。中間群は高湿群よりも，発赤面積が有意に小さかった（除圧後48 時間, p＜0.05）。発赤の重症度を示すOptical Density は，中間群では高湿群よりも有意に低かった（除圧後24，48時間，p＜0.01，p＜0.05）。総潰瘍出現数は，高湿群が有意に多く，中間群が有意に少なかった（p＜0.05）。　圧迫部へ湿度を40 ～ 50% 程度に調整した空気を通気することで圧迫性皮膚傷害の発生率を低下させ，早期に治癒することが示された。また，圧迫部へ70% 以上または25% 程度に調整した空気を通気すると，圧迫性皮膚傷害の発生率が増加し，治癒が遅延することが示された。圧迫された皮膚，いわゆる褥瘡の発症が予想される場合，圧迫中に皮膚湿度を適切に調整することにより褥瘡の発症予防および早期に治癒する可能性が示唆された

酸素局所供給による皮膚圧迫性傷害の発症予防効果

　褥瘡とは，「寝たきりなどによって体重で圧迫されている場所の血流が悪くなったり滞ることで，皮膚の一部が赤い色味をおびたり，ただれたり，傷ができてしまうこと」とされ，長時間の圧迫等により皮膚の細胞に十分な酸素や栄養が行き渡らなくなることにより発症する。一方で，皮膚の細胞は必要な酸素の一部を外気から吸収しているため，圧迫部に対して外部から酸素を供給することで褥瘡発生に予防的な効果を得られることが考えられる。本研究ではヘアレスラットを用いて圧迫部皮膚に局所的に外部から空気または酸素濃度１００ % 濃度の気体（純酸素）を供給することで皮膚細胞の酸素不足を軽減し，褥瘡予防に対する効果を検討した。　本研究においては空気，純酸素を供給した群では無通気群よりも圧迫部における発赤面積，潰瘍発生率が低く，圧迫部に対する通気は褥瘡予防に効果的であることが示唆された。特に純酸素を供給した群において潰瘍は発生せず，発赤消失までの時間も短時間であった。　過剰な量の酸素投与は細胞に対する毒性が報告されている。しかしながら本研究においては純酸素投与が褥瘡予防に最も効果的な結果を示した。手術等で姿勢が固定されている際にも圧迫部に対し通気を行うことで褥瘡予防へ繋がる可能性が考えられる。今後より効果的な酸素濃度や臨床への応用についてもさらなる検討を重ねていきたい。　Pressure injuries consist of redness, ulceration and wounds caused by the obstructionof blood flow due to sustained mechanical load and the deformation of soft tissue. Onemechanism of pressure injuries is a lack of oxygen and nutrition supply due to theblocking of peripheral blood flows. Skin cells can absorb oxygen from the air; therefore,it is considered that a preventive effect on the development of pressure injuries can beobtained by supplying oxygen topically to the compressed area. In this study, we discusspressure injury prevention via the supply of oxygen (room air or 100% oxygen) to thecompressed skin of a hairless rat for the purpose of preventing a lack of oxygen in theskin cells.　As a result, the area of redness and incidence rate of pressure ulcers in the compressedareas were smaller in the room air group and 100% oxygen group, when compared to acontrol group. In particular, in the 100% oxygen group, there was no ulcer incidence andthe period of sustained skin redness was shorter.　Although it is reported that excessive oxygen supply produces a toxic effect on humancells, the pure oxygen group showed the most effective results in the present study. Ifposture is to be fixed for a long time, e.g. for an operation, topical oxygen supply to thecompressed skin area may be effective. We hope to discuss the most effective oxygenconcentration and clinical application in a future study