Structural requirement of leucine for activation of p70 S6 kinase

AbstractThe addition of leucine induced activation of p70S6k in amino acid-depleted H4IIE cells. Whereas the activation of p70S6k by leucine was transient, the complete amino acid stimulated p70S6k more persistently. The effect of leucine on p70S6k was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70S6k, indicating that the structural requirement of leucine to induce p70S6k activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70S6k and the other derivatives acted as inhibitors against the leucine-induced activation of p70S6k

Development of Heated Narrow Channels with Enhanced Liquid Supply in Forced Convective Boiling

Abstract Heat generation density from semiconductor devices increases with the rapid development of electronic technology. The cooling system using boiling two-phase phenomena attracts much attention because of its high heat removal potential. Most of heat transfer researches concerning the development of electronic devices are conducted for the cooling of small semiconductor chips, while there are limited numbers of innovative investigations for the cooling of a large area at extremely high heat flux larger than 2×10 6 W/m 2 . The technology can be applied to the cooling systems in space, e.g., cooling of laser medium in solar power satellites when solar energy is converted to laser power. To develop compact and high-performance cooling systems, a structure of narrow heated channel between parallel plates with auxiliary unheated channel was devised and tested by using water in three different kinds of experimental conditions. One of liquid supply method, where liquid is supplied to both of the main heated and the auxiliary unheated channel keeping the exit of the auxiliary channel closed, gives the highest CHF value at total volumetric flow rates more than 3.0×10 -5 m 3 /s and 2mm gap size of main heated channel

New Surgical Procedure for Pancreas Head

In this study, we demonstrate two new methods for pancreaticoduodenectomy (PD). One method is the mini‐laparotomic PD by Shuriken‐shaped umbilicoplasty with the real‐time moving window‘s method. The other method is the new pancreaticojejunostomy (PJ) by punctured stent slide guiding method (PSSGM). This procedure could be performed by complete mini‐laparotomy under direct vision, and the final major wound is only 2 cm of round navel. PSSGM prevents the difference of caliber between pancreatic anastomosis and the inside out of jejunal mucosa in theory. Ten cases of mini‐lap PD were successfully performed under new PJ anastomosis. The pancreatic leakage (PL) was only one case of ISGPF grade A, and its frequency was 9% (1/11). Our mini‐lap PD by Shuriken‐shaped umbilicoplasty might be a useful way for overcoming the obstacles about safety, complication risk, cosmetic demand, and medical cost compared to laparoscopic PD. Also, our new device of PJ reconstruction by PSSGM might be an easy and useful device for the prevention of PL

Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst

The authors present a method for flattening SiC surfaces with Pt as a catalyst in HF solution. The mechanism for flattening SiC surfaces is discussed. The flattened 4H-SiC (0001) surface is composed of alternating wide and narrow terraces with single-bilayer-height steps, which are induced by the rate difference of the catalytic reactions between adjacent terraces. Scanning tunneling microscopy images reveal a 1×1 phase on the terraces. The 1×1 phase is composed of coexisting of F- and OH-terminated Si atoms, which originate from the polarization of the underlying Si-C bonds. © 2007 American Institute of Physics.Kenta Arima, Hideyuki Hara, et al. "Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst", Appl. Phys. Lett. 90(20), 202106 (2007) https://doi.org/10.1063/1.2739084

Home visits provide a better understanding of the psychopathology of a case of eating disorder

Eating disorders (ED) are characterized by abnormal eating behaviors that negatively affect the patient’s medical or psychiatric health, with symptoms usually developing during adolescence. Treatment for ED varies across patients and the disease time-course, reflecting differences in psychopathology and medical comorbidities. Here, we provide a brief review of the standard management strategy for ED and emphasize the importance of individualized treatment. To illustrate this, we present a case of ED in which a halt in development was observed during a home visit, which is an unusual component in the treatment of ED. Furthermore, as a result of our collective experience in treating ED, we recognize that discussion among multidisciplinary healthcare professionals is important to improve outcomes

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy

Bronchial thermoplasty for severe asthma

Despite the relatively short follow-up period in our previous study, we had reported that increased cough reflex sensitivity (CRS) may predict the efficacy of bronchial thermoplasty (BT) for treating asthma. Herein, we examined whether CRS predicts the efficacy of BT 2 years after the final BT treatment. We also investigated the influence of BT on CRS. We reviewed 10 patients 2 years after their final BT treatment. CRS, asthma-related symptoms, asthma exacerbations, and cough-related quality of life were assessed at baseline and 2 years after BT. Five patients responded positively to BT (BT responders) and their asthma control improved. No significant difference in CRS at baseline was detected between the BT responders and nonresponders. In contrast, BT responders exhibited significant improvements in CRS 2 years after BT. CRS at baseline could not predict the BT efficacy after 2 years. This is the first report demonstrating BT desensitized CRS in consecutive case series

Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model

Background: Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods: In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results: Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Conclusions: Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice

Asthma-COPD overlap : prevalence and features

Background Asthma-COPD overlap (ACO) is a disease that shares clinical features of both asthma and COPD. The purpose of this study is to investigate the prevalence and clinical features of ACO. Methods We retrospectively reviewed data for 170 patients with persistent airflow limitation and diagnosed them according to “The Japanese Respiratory Society Guidelines for the Management of ACO 2018”. Results Of the 170 patients, 111 were diagnosed as follows : COPD (74 patients, 66.6%), ACO (34 patients, 30.6%), and asthma (3 patients, 2.8%). There was no significant difference in clinical features between ACO and COPD patients. The following pulmonary function tests were significantly lower in ACO than in COPD patients : forced expiratory volume in 1 second/forced vital capacity, peak expiratory flow, maximal mid-expiratory flow, and the maximum expiratory flow at 50% and 75%. The following respiratory impedance parameters were significantly higher in ACO than in COPD patients : respiratory resistance (Rrs) at 5 Hz (R5), Rrsat 20 Hz (R20), R5-R20, and low-frequency reactance area. Conclusions About 30% of patients with persistent airflow limitation were diagnosed with ACO. ACO patients had lower lung function and higher respiratory impedance compared with COPD patients