A neonatal case of an elongated soft palate

The development of stridor and periodic desaturation in a 2-day-old neonate born at term lead to the suspicion of upper airway obstruction. The patient underwent flexible fiberoptic laryngo-tracheo-bronchoscopy and was diagnosed as having an elongated soft palate and secondary mild pharyngomalacia. Early intervention with high PEEP therapy using nasal CPAP led to improvement in the patient condition

Broadband multi-layer anti-reflection coatings with mullite and duroid for half-wave plates and alumina filters for CMB polarimetry

A broadband two-layer anti-reflection (AR) coating was developed for use on a sapphire half-wave plate (HWP) and an alumina infrared (IR) filter for cosmic microwave background (CMB) polarimetry. Measuring tiny CMB B-mode signals requires maximizing the number of photons reaching the detectors and minimizing spurious polarization due to reflection with an off-axis incident angle. However, a sapphire HWP and an alumina IR filter have high refractive indices of about 3.1, and an AR coating must be applied to them. Thermally sprayed mullite and Duroid 5880LZ were selected in terms of index and coefficient of thermal expansion for use at cryogenic temperatures. With these materials, the reflectivity was reduced to about 2% at 90/150 GHz and <1% at 220/280 GHz. The design, fabrication, and optical performance evaluation of the AR coatings are described. The coatings were used in a current ground-based CMB experiment called the Simons Array. They could also be applied to next-generation CMB experiments, such as the Simons Observatory.Comment: 7 pages, 4 figure

Effects of Highly Absorbable Curcumin in Patients with Impaired Glucose Tolerance and Non-Insulin-Dependent Diabetes Mellitus

Oxidative stress is enhanced by various mechanisms. Serum oxidized low-density lipoprotein (LDL) is a useful prognostic marker in diabetic patients with coronary artery disease. To examine the effects of Theracurmin®, a highly absorbable curcumin preparation, on glucose tolerance, adipocytokines, and oxidized LDL, we conducted a double-blind placebo-controlled parallel group randomized trial in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. We randomly divided the patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus and stable individuals into the placebo group and the Theracurmin® (180 mg daily for 6 months) group. Of the 33 patients analyzed, 18 (14 males and 4 females) were administered placebo and 15 (9 males and 6 females) were administered Theracurmin®. The patient characteristics did not differ between the two groups. The primary endpoint, HbA1c, did not differ significantly between the two groups. However, the level of α1-antitrypsin-low-density lipoprotein (AT-LDL), the oxidized LDL, significantly increased (p = 0.024) in the placebo group from the beginning of the trial up to 6 months, although there was no such change in the Theracurmin® group. The percentage change in BMI from the beginning of the trial up to 6 months tended to be higher in the Theracurmin® group than in the placebo group. Patients in the Theracurmin® group tended to have a larger percentage change in adiponectin and LDL-C than those in the placebo group. Patients in the Theracurmin® group showed a smaller percentage change in AT-LDL than those in the placebo group. This study suggests that the highly absorbable curcumin could potentially inhibit a rise in oxidized LDL in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. This trial is registered with UMIN000007361

ANGPTL4 Expression Is Increased in Epicardial Adipose Tissue of Patients with Coronary Artery Disease

Epicardial adipose tissue (EAT) is known to affect atherosclerosis and coronary artery disease (CAD) pathogenesis, persistently releasing pro-inflammatory adipokines that affect the myocardium and coronary arteries. Angiopoietin-like 4 (ANGPTL4) is a protein secreted from adipose tissue and plays a critical role in the progression of atherosclerosis. Here, the expression of ANGPTL4 in EAT was investigated in CAD subjects. Thirty-four consecutive patients (13 patients with significant CAD; 21 patients without CAD) undergoing elective open-heart surgery were recruited. EAT and pericardial fluid were obtained at the time of surgery. mRNA expression and ANGPTL4 and IL-1β levels were evaluated by qRT-PCR and ELISA. The expression of ANGPTL4 (p = 0.0180) and IL-1β (p < 0.0001) in EAT significantly increased in the CAD group compared to that in the non-CAD group and positively correlated (p = 0.004). Multiple regression analysis indicated that CAD is a contributing factor for ANGPTL4 expression in EAT. IL-1β level in the pericardial fluid was significantly increased in patients with CAD (p = 0.020). Moreover, the expression of ANGPTL4 (p = 0.004) and IL-1β (p < 0.001) in EAT was significantly increased in non-obese patients with CAD. In summary, ANGPTL4 expression in EAT was increased in CAD patients

Pyrazole-Curcumin Suppresses Cardiomyocyte Hypertrophy by Disrupting the CDK9/CyclinT1 Complex

The intrinsic histone acetyltransferase (HAT), p300, has an important role in the development and progression of heart failure. Curcumin (CUR), a natural p300-specific HAT inhibitor, suppresses hypertrophic responses and prevents deterioration of left-ventricular systolic function in heart-failure models. However, few structure–activity relationship studies on cardiomyocyte hypertrophy using CUR have been conducted. To evaluate if prenylated pyrazolo curcumin (PPC) and curcumin pyrazole (PyrC) can suppress cardiomyocyte hypertrophy, cultured cardiomyocytes were treated with CUR, PPC, or PyrC and then stimulated with phenylephrine (PE). PE-induced cardiomyocyte hypertrophy was inhibited by PyrC but not PPC at a lower concentration than CUR. Western blotting showed that PyrC suppressed PE-induced histone acetylation. However, an in vitro HAT assay showed that PyrC did not directly inhibit p300-HAT activity. As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined. Phosphorylation of p300 by Cdk9 was suppressed by PyrC. Immunoprecipitation-WB showed that PyrC inhibits Cdk9 binding to CyclinT1 in cultured cardiomyocytes. PyrC may prevent cardiomyocyte hypertrophic responses by indirectly suppressing both p300-HAT activity and RNA polymerase II transcription elongation activity via inhibition of Cdk9 kinase activity

Anti-inflammatory Action of Curcumin and Its Use in the Treatment of Lifestyle-related Diseases

Chronic inflammation plays a significant role in lifestyle-related diseases, such as cardiovascular diseases and obesity/impaired glucose tolerance. Curcumin is a natural extract that possesses numerous physiological properties, as indicated by its anti-inflammatory action. The mechanisms underlying these effects include the inhibition of nuclear factor-kappaB and Toll-like receptor 4-dependent signalling pathways and the activation of a peroxisome proliferator-activated receptor-gamma pathway. However, the bioavailability of curcumin is very low in humans. To resolve this issue, several drug delivery systems have been developed and a number of clinical trials have reported beneficial effects of curcumin in the management of inflammation-related diseases. It is expected that evidence regarding the clinical application of curcumin in lifestyle-related diseases associated with chronic inflammation will accumulate over time

The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice

Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice