Design Study of CANGAROO-III, Stereoscopic Imaging Atmospheric Cherenkov Telescopes for sub-TeV Gamma-ray

CANGAROO-III is an Imaging Atmospheric Cherenkov Telescope (IACT) array of four 10 m telescopes for very high energy (sub-TeV) gamma-ray astronomy. A design study of the CANGAROO-III telescope system was carried out using the Monte Carlo technique in order to optimize the pixel size and the telescope spacing. Studies were also made of observations at low elevation angles.Comment: 17pages, 13 figures, elsart, to appear in Astro. Part. Phy

The impact of plaque type on strut embedment/protrusion and shear stress distribution in bioresorbable scaffold

AIMS: Scaffold design and plaque characteristics influence implantation outcomes and local flow dynamics in treated coronary segments. Our aim is to assess the impact of strut embedment/protrusion of bioresorbable scaffold on local shear stress distribution in different atherosclerotic plaque types. METHODS AND RESULTS: Fifteen Absorb everolimus-eluting Bioresorbable Vascular Scaffolds were implanted in human epicardial coronary arteries. Optical coherence tomography (OCT) was performed post-scaffold implantation and strut embedment/protrusion were analysed using a dedicated software. OCT data were fused with angiography to reconstruct 3D coronary anatomy. Blood flow simulation was performed and wall shear stress (WSS) was estimated in each scaffolded surface and the relationship between strut embedment/protrusion and WSS was evaluated. There were 9083 struts analysed. Ninety-seven percent of the struts (n = 8840) were well-apposed and 243 (3%) were malapposed. At cross-section level (n = 1289), strut embedment was significantly increased in fibroatheromatous plaques (76 ± 48 µm) and decreased in fibrocalcific plaques (35 ± 52 µm). Compatible with strut embedment, WSS was significantly higher in lipid-rich fibroatheromatous plaques (1.50 ± 0.81 Pa), whereas significantly decreased in fibrocalcified plaques (1.05 ± 0.91 Pa). After categorization of WSS as low (<1.0 Pa) and normal/high WSS (≥1.0 Pa), the percent of low WSS in the plaque subgroups were 30.1%, 31.1%, 25.4%, and 36.2% for non-diseased vessel wall, fibrous plaque, fibroatheromatous plaque, and fibrocalcific plaque, respectively (P-overall < 0.001). CONCLUSION: The composition of the underlying plaque influences strut embedment which seems to have effect on WSS. The struts deeply embedded in lipid-rich fibroatheromas plaques resulted in higher WSS compared with the other plaque types

Vulnerable plaques and patients: state-of-the-art

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of 'high-risk' plaques occurring in 'vulnerable' patients

The influence of implantation techniques on lesion oriented-outcomes in Absorb BVS and Xience EES lesions treated in routine clinical practice at complete three year follow-up: AIDA trial QCA substudy

It has been hypothesized that dedicated optimized Absorb BVS implantation techniques might mitigate the risk of adverse events such as target vessel

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

Endothelial shear stress and vascular remodeling in bioresorbable scaffold and metallic stent

Background and aims: The impact of endothelial shear stress (ESS) on vessel remodeling in vessels implanted with bioresorbable scaffold (BRS) as compared to metallic drug-eluting stent (DES) remains elusive. The aim of this study was to determine whether the relationship between ESS and remodeling patterns differs in BRS from those seen in metallic DES at 3-year follow-up. Methods: In the ABSORB II randomized trial, lesions were investigated by serial coronary angiography and intravascular ultrasound (IVUS). Three-dimensional reconstructions of coronary arteries post-procedure and at 3 years were performed. ESS was quantified using non-Newtonian steady flow simulation. IVUS cross-sections in device segment were matched using identical landmarks. Results: Paired ESS calculations post-procedure and at 3 years were feasible in 57 lesions in 56 patients. Postprocedure, median ESS at frame level was higher in BRS than in DES, with marginal statistical significance (0.97 ± 0.48 vs. 0.75 ± 0.39 Pa, p = 0.063). In the BRS arm, vessel area and lumen area showed larger increases in the highest tercile of median ESS post-procedure as compared to the lowest tercile. In contrast, in DES, no significant relationship between median ESS post-procedure and remodeling was observed. In multivariate analysis, smaller vessel area, larger lumen area, higher plaque burden post-procedure, and higher median ESS post-procedure were independently associated with expansive remodeling in matched frames. Only in BRS, younger age was an additional significant predictor of expansive remodeling. Conclusions: In a subset of lesions with large plaque burden, shear stress could be associated with expansive remodeling and late lumen enlargement in BRS, while ESS had no impact on vessel dimension in metallic DES

Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis.

Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG–/–) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG–/–mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG–/–mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/β-catenin signaling and induced alveolar bone formation in OPG–/–mice. Expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was significantly lower in tibiae of OPG–/–mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG–/–mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG–/–mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG–/–mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis

Vulnerable plaques and patients: state-of-the-art

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of 'high-risk' plaques occurring in 'vulnerable' patients

MRL/MpJ-Fas(lpr) mice show abnormalities in ovarian function and morphology with the progression of autoimmune disease

The immune system is known to affect reproductive function, and maternal-fetal immune tolerance is essential for a successful pregnancy. To investigate the relationship between autoimmune disease and female reproductive function, we performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice, autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas(lpr) (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset. Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice of the other two strains, respectively. Histological analysis at 3 months revealed that the number of primordial follicles was smaller in MRL-background mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months, and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months, respectively. In particular, MRL/lpr mice showed numerous infiltrating lymphocytes within the ovarian interstitia, and partially stratified ovarian surface epithelia with more developed microvilli than that observed in C57BL/6 mice at 6 months. No significant differences in serum hormone levels were observed between the strains. In conclusion, MRL/lpr mice display altered ovarian development, morphology and function consistent with the progression of severe autoimmune disease, as these findings are less severe in MRL/+ counterparts