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Ferromagnetic shape memory alloys (FSMAs), which are potential candidates for future technologies (i.e., actuators in robots), have been paid much attention for their high work per volume and rapid response as external stimulation, such as a magnetic field, is imposed. Among all the FSMAs, the Ni-Mn-Ga-based alloys were considered promising materials due to their appropriate phase transformation temperatures and ferromagnetism. Nevertheless, their intrinsic embrittlement issue and sluggish twin motion due to the inhibition of grain boundaries restrict their practicability. This study took advantage of the single-crystal Ni-Mn-Ga cube/silicone rubber composite materials to solve the two aforementioned difficulties. The single-crystal Ni-Mn-Ga cube was prepared by using a high-temperature alloying procedure and a floating-zone (FZ) method, and the cubes were verified to be the near-{100} p Ni-Mn-Ga alloy. Various room temperature (RT) curing silicone rubbers were utilized as matrix materials. Furthermore, polystyrene foam particles (PFP) were used to provide pores, allowing a porous silicone rubber matrix. It was found that the elastic modulus of the silicone rubber was successfully reduced by introducing the PFP. Additionally, the magnetic field-induced martensite variant reorientation (MVR) was greatly enhanced by introducing a porous structure into the silicone rubber. The single-crystal Ni-Mn-Ga cube/porous silicone rubber composite materials are considered to be promising materials for applications in actuators.

The phase stability, mechanical properties, and functional properties of Ti-5.5Al-11.8[Mo] eq alloys are focused on in this study by substituting 3d transition metal elements (V, Cr, Co, and Ni) for Mo as β-stabilizers to achieve similar β phase stability and room temperature (RT) superelasticity. The ternary alloy systems with the equivalent chemical compositions of Ti-5.5Al-17.7V, Ti-5.5Al-9.5Cr, Ti-5.5Al-7.0Co, and Ti-5.5Al-9.5Ni (mass%) alloys were selected as the target materials based on the Mo equivalent formula, which has been applied for the Ti-5.5Al-11.8Mo alloy in the literature. The fundamental mechanical properties and functionalities of the selected alloys were examined. The β phase was stabilized at RT in all alloys except for the Ti-Al-V alloy. Among all alloys, the Ti-Al-Ni alloy exhibited superelasticity in the cyclic loading-unloading tensile tests at RT. As a result, similar to the Ti-5.5Al-11.8Mo mother alloy, by utilizing the Mo equivalent formula to substitute 3d transition metal elements for Mo, a RT superelasticity was successfully imposed.

Intracardiac thrombosis formation in patients in sinus rhythm is a rare phenomenon. An 84-year-old woman was admitted because of worsening dyspnea on exertion. An electrocardiogram showed sinus rhythm, left atrial overload, marked left axis deviation, low voltage, and poor r-wave progression in leads V1-4. An echocardiogram showed relatively preserved left ventricular ejection fraction with minimal wall thickening. Her serum level of B-type natriuretic peptide (931 pg/mL) was markedly elevated and a diagnosis of worsening heart failure was made. During the course of treatment for heart failure, she was complicated by acute abdominal aortic thromboembolism together with left atrial thrombus. An emergency abdominal aortic thrombectomy was followed by the removal of a left atrial thrombus 2 days later. Left ventricular biopsy performed during the surgery revealed amyloid deposits in the myocardial interstitium. Immunohistochemical study confirmed the diagnosis of transthyretin cardiac amyloidosis. It is postulated that the risk of intracardiac thrombosis and systemic embolism is increased even in sinus rhythm in patients with cardiac amyloidosis.

Ni-Mn-Ga single crystals (SC) exhibiting a giant magnetic field induced strain (MFIS), resulting from twin boundaries rearrangements, are excellent materials for novel actuators although enhanced brittleness and high costs are remaining the issues for applications. In polycrystalline state Ni-Mn-Ga alloys show small MFIS due to grain boundary constraints. By simple size reduction of the mentioned materials it is hardly possible to create quasi-two-dimensional MFIS actuators on the microscale with a pertinent out-of-plane performance. In pursuit of the trend for next generation materials and functions by design, in the present work we have developed a laminate composite as a prototype of microactuator with the out-of-plane stroke being driven by a framework of magnetostrain responsive Ni-Mn-Ga microparticles. The laminate consisted of the layer of crystallographically oriented Ni-Mn-Ga semi-free SC microparticles sandwiched between bonding polymer and Cu foils. Such design provided a particles isolation with a minimum constraint condition from the polymer. MFIS of the individual particles and the whole laminate composite was investigated by X-ray micro-CT 3D imaging. Both particles and laminate exhibited the same recoverable out-of-plane stroke produced by the particles´ MFIS of around 3% under 0.9 T. The developed microactuator design is promising for applications in the areas of micro-robotics, optical image stabilization in cameras, pumps for microfluidics etc., (© 2023. The Author(s).)

Aims: The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-effects, we used 123I-labelled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT., Methods and Results: We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anaesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering β3-agonist. Furthermore, exposing mice to cold stress at 4°C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labelled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labelled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analysed the expression of known oxLDL receptors (e.g. SR-A, CD36, and LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT., Conclusion: We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation., Competing Interests: Conflict of interest: H.H. received research grants from Tosoh Bioscience, Inc. T.S. is an inventor of a patents and received consulting fee from PreMedica Inc., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

For the further development of biocompatible metastable β (bcc) Ti alloys, the purpose of this study is to evaluate the potential of bismuth (Bi) addition in terms of shape memory properties and phase stability. It was found that the shape memory effect appeared in Ti-5Cr-1.6Bi (mol%) alloy. However, permanent (unrecoverable) deformation due to dislocations or twinning was also introduced simultaneously from the early stage of deformation. Regarding the formation of isothermal ω phase and the resulting hardness change by aging, it was found that the hardness change was large and that the isothermal ω phase formed in Ti-5Cr-1.6Bi alloy, while age hardening was small and no isothermal ω phase formed in Ti-5Cr-6.1Bi alloy. These results indicate the suppression of not only athermal ω but also isothermal ω phase by Bi addition. However, considering the fact that the alloy becomes brittle when Bi addition is over 3 mol%, it can be concluded that 1-3 mol% Bi addition is worth for the improvement of shape memory effect, suppression of ω phase, X-ray imaging, magnetic resonance imaging, and biocompatibility in metastable β Ti alloys., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This study investigated the association between placental pathology and fetal heart failure., Methods and results: Singletons with a congenital heart defect (CHD) and/or arrhythmia (n=168) and gestational age-matched controls (n=52) were included in the study. The associations between macro- and microscopic abnormal findings of the placenta and the severity of fetal heart failure were evaluated using the cardiovascular profile (CVP) score. Nine features were microscopically identified and assessed in sections of the placenta: premature villi, edematous villi, fibrotic villi, chorioamnionitis, chorangiosis, fibrin deposition, subchorionic hematoma, infarcted villi, and nucleated red blood cells in villous vessels. Among singletons with CHD and/or arrhythmia, the final CVP score was ≥8 in 140 cases, 6 or 7 in 15 cases, and ≤5 in 13 cases. Microscopic analysis showed that the frequency and severity of premature and edematous villi and increased nucleated red blood cells in villous vessels were greater in cases of fetal heart failure. These microscopic findings were more common and severe in cases with a final CVP score ≤5 than in gestational age-matched controls. The prevalence of abnormal macroscopic findings of the placenta and umbilical cord was similar regardless of the severity of fetal heart failure., Conclusions: Premature and edematous villi and increased nucleated red blood cells in villous vessels were correlated with the severity of fetal heart failure in cases of CHD and/or arrhythmia.

Polyethylene terephthalate (PET) is known to be highly inert, and this makes it difficult to be metallized. In addition, Pt electroless plating is rarely reported in the metallization of polymers. In this study, the metallization of biocompatible Pt metal is realized by supercritical CO 2 (sc-CO 2 )-assisted electroless plating. The catalyst precursor used in the sc-CO 2 catalyzation step is an organometallic compound, palladium (II) acetylacetonate (Pd(acac) 2 ). The electrical resistance is evaluated, and a tape adhesion test is utilized to demonstrate intactness of the Pt layer on the PET film. The electrical resistance of the Pt/PET with 60 min of the Pt deposition time remains at a low level of 1.09 Ω after the adhesion test, revealing positive effects of the sc-CO 2 catalyzation step. A tensile test is conducted to evaluate the mechanical strength of the Pt/PET. In-situ electrical resistances of the specimen are monitored during the tensile test. The fracture strength is determined from the stress value when the short circuit occurred. The fracture strength is 33.9 MPa for a specimen with 30 min of the Pt deposition time. As the Pt deposition time increases to 45 min and 60 min, the fracture strengths reach 52.3 MPa and 65.9 MPa, respectively. The promoted fracture strength and the decent electrical conductivity demonstrate the advantages toward biomedical devices.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for critically ill patients all over the world; however, comprehensive survey regarding the relationship between VA-ECMO duration and prognosis is limited. We conducted a survey of VA-ECMO patients in the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), which was a health insurance claim database study among cardiovascular centers associated with the Japan Circulation Society, between April 2012 and March 2016. Out of 13,542 VA-ECMO patients, we analyzed 5766 cardiovascular patients treated with VA-ECMO. 68% patients used VA-ECMO only for 1 day and 93% had VA-ECMO terminated within 1 week. In multivariate analysis, the hazard ratio of 1-day support was significantly high at 1.72 (95% confidence intervals; 95% CI 1.53-1.95) (p < 0.001), while that of 2-day [0.60 (95% CI 0.49-0.73)], 3-day [0.75 (95% CI 0.60-0.94)], 4-day [0.43 (95% CI 0.31-0.60)] and 5-day support [0.62 (95% CI 0.44-0.86)] was significantly low. Comprehensive database analysis of JROAD-DPC revealed that cardiovascular patients who were supported with VA-ECMO for 2-5 days showed lower mortality. The optimal VA-ECMO support window should be investigated in further studies., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Cardiogenic unilateral pulmonary edema (UPE) has been reported as an unusual condition and to occur in association with severe mitral regurgitation (MR). However, the prevalence of UPE in patients with severe MR remains unknown. Methods and Results: Among 143 consecutive patients with chordal rupture and significant MR, 38 patients with acute severe MR were studied. The prevalence of UPE was 50% (19 patients); all these patients had right-sided UPE. Eight (21%) patients had bilateral pulmonary edema (BPE). All 8 patients with BPE and 18 of 19 patients with UPE had chordal rupture of the posterior leaflet. All patients with UPE and BPE had severe MR with similar left atrial size. Chest radiographs taken ≤48 h from symptom onset diagnosed UPE in 15 of 19 (79%) patients and BPE in 3 of 8 (38%) patients (P=0.037). Chest radiographs taken >48 h from symptom onset diagnosed UPE in 4 (21%) patients and BPE in 5 (62%) patients (P=0.037). Conclusions: The prevalence of UPE was estimated as 50%; it was most frequently right sided and almost always associated with chordal rupture of the posterior leaflet. UPE is not rare, but common, particularly shortly after the development of acute severe MR caused by chordal rupture., Competing Interests: All authors have no conflict of interest to disclose., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Background: Acute coronary syndrome (ACS) with occlusion of the left circumflex coronary artery (LCX) poses diagnostic problems that may lead to a delay in reperfusion. Methods and Results: From a group of 1,269 consecutive patients with ACS, 138 patients with ACS due to LCX occlusion were analyzed for clinical, electrocardiographic, and angiographic presentations, as well as door-to-balloon (DTB) time. Electrocardiographic changes were classified into 4 patterns: ST-segment elevation in inferior/lateral leads (ST-E); ST-segment depression in V1-V4 (ST-D); no significant ST changes (No-ST); and others. The No-ST group was associated with a longer DTB time (P<0.0001) compared with the ST-E and ST-D groups. Compared with the No-ST and ST-E groups, the ST-D group presented with a more advanced Killip class (P=0.003), greater peak creatine phosphokinase (P=0.007) and peak creatine kinase-MB (P=0.006), more frequent proximal LCX occlusion (P=0.007), and worse 1-year outcomes (P=0.0034). Conclusions: One-third of ACS patients with LCX occlusion showed no ST-segment changes, resulting in significantly longer DTB time. Improving diagnostic accuracy is challenging but critical to avoid delayed reperfusion in these patients without electrocardiographic changes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Plasma adrenomedullin concentrations are reportedly elevated in patients with renal failure; however, the underlying mechanism is unclear. In this study, we investigated the plasma clearance of synthetic human adrenomedullin (AM) in two models of rats with renal dysfunction; one was induced by subcutaneous injection of mercury chloride (RD-Ag) and the other by completely blocking bilateral renal blood flow (RD-Bl). Sixty minutes after starting intravenous AM infusion, AM levels in RD-Ag, RD-Bl, and rats with normal renal function (NF) were still increased slightly; however, plasma AM levels in RD-Ag rats were approximately three times as high as in RD-Bl and NF rats. Plasma AM disappearance after the end of treatment was similar among the three groups. Pharmacokinetic analysis revealed that elevated plasma AM in RD-Ag rats may be caused by a reduced volume of distribution. The adrenomedullin functional receptor is composed of heterodimers, including GPCR, CLR (calcitonin receptor-like receptor, CALCRL), and the single transmembrane proteins, RAMP2 or RAMP3 (receptor activity modifying protein). Calcrl expression was downregulated in the lungs and kidneys of RD-Ag rats. Furthermore, the plasma concentration of exogenous AM was elevated in mice deficient in vascular endothelium-specific Ramp2 . These results suggest that decreased plasma AM clearance in RD-Ag is not due to impaired renal excretion but to a decreased volume of distribution caused by a reduction in adrenomedullin receptors.

In view of the urgent demands of shape memory alloys (SMAs) for biomedical applications due to the world population aging issue, the mechanical properties and functionalities of the biocompatible Ti-Au-Cr-based SMAs, which are tailored by Ta additions, have been developed in this study. The quaternary SMAs were successfully manufactured by physical metallurgy techniques and their mechanical properties and functionalities were examined. In the continuous tensile tests, it was found that the correlation between the yielding strength and phase stability followed a typical trend of mechanical behavior of SMAs, showing the lowest yielding strength at the metastable β-parent phase. Functional mappings between the alloy strength and elongation revealed that compared to the Ta-free specimen, the ductility was promoted 50% while the strength remained intact through the 4 at.% introduction of Ta. Slight shape recovery was observed in the cyclic loading-unloading tensile tests during the unloading process and the highest shape recovery was found in the Ti-4 at.% Au-5 at.% Cr-4 at.% Ta specimen. This indicates that the 4 at.% Ta tailored Ti-Au-Cr SMAs could be a promising material for biomedical applications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ghrelin, an n-octanoyl-modified 28-amino-acid-peptide, was first discovered in the human and rat stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin-GHS-R1a signaling regulates feeding behavior and energy balance, promotes vascular activity and angiogenesis, improves arrhythmia and heart failure, and also protects against cardiovascular disease by suppressing cardiac remodeling after myocardial infarction. Ghrelin's cardiovascular protective effects are mediated by the suppression of sympathetic activity; activation of parasympathetic activity; alleviation of vascular endothelial dysfunction; and regulation of inflammation, apoptosis, and autophagy. The physiological functions of ghrelin should be clarified to determine its pharmacological potential as a cardiovascular medication.

Physiological changes including altered nutritional status influence disease progression and survival in patients with amyotrophic lateral sclerosis (ALS). Ghrelin affects the nutritional status by regulating appetite and energy expenditure, and also has neuroprotective effects. To investigate the association between ghrelin and ALS prognosis, we analyzed plasma acylated-ghrelin levels in 33 patients with ALS. Compared among ALS patients, male had lower plasma ghrelin levels than female, although disease specificity is unknown. ALS patients, especially male ALS patients, with low plasma ghrelin levels (<15 fmol/mL) had significantly shorter post-examination survival times than those with high plasma ghrelin levels (≥15 fmol/mL). Univariate and multivariate analyses revealed a significant effect of ghrelin levels on post-examination survival. Immunohistochemical study of autopsied stomach samples from 8 of 33 patients revealed that the population of ghrelin-positive cells tended to be reduced in the low-plasma ghrelin group than in the high-plasma ghrelin group. Our findings suggest that ghrelin levels are an independent predictor of survival in ALS, especially male ALS patients, and the ghrelin-positive cells may decrease in ALS with low plasma ghrelin. Thus, reduced ghrelin secretion may be associated with poor prognosis among patients with ALS., (Copyright © 2021. Published by Elsevier B.V.)

Lactic acid bacteria (LAB) have been attracting attention for their effects on innate immunity, and therefore, it is required to develop an efficient culturing method while maintaining their functionality. In this study, first, we compared the growth and functionality of LAB cultured on food grade (FG) medium with those on standard LAB medium and found that LAB cultured in the FG medium were smaller in cell size with high yield and had a higher ability to induce IL-12(p40) production by murine spleen cells in vitro. Moreover, the higher the glutamate concentration in the medium, the smaller the cell size, and the higher the yield and the higher the ability to induce IL-12 production. Addition of glutamate to the culture medium changes the size of LAB and affects their ability to induce IL-12(p40) production. In conclusion, regulating the concentration of glutamate would be important in the efficient culturing of functional LAB., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The achievement of room-temperature (RT) superelasticity in a Ti-Mo-Al ternary alloy system through the addition of a relatively high concentration of Al to manipulate the phase stability of the ω phase is realized in this study. The composition of the Ti-6 mol% Mo (Ti-11.34 mass% Mo) alloy was designated as the starting alloy, while 5 mol% Al (=2.71 mass% Al) and 10 mol% Al (=5.54 mass% Al) were introduced to promote their superelastic behavior. Among the alloys, Ti-6 mol% Mo-10 mol% Al alloy, which was investigated for the very first time in this work, performed the best in terms of superelasticity. On the other hand, Ti-6 mol% Mo and Ti-6 mol% Mo-5 mol% Al alloys exhibited a shape memory effect upon heating. It is worth mentioning that in the transmission electron microscopy observation, ω phase, which appeared along with β-parent phase, was significantly suppressed as Al concentration was elevated up to 10 mol%. Therefore, the conventional difficulties of the inhibited RT superelasticity were successfully revealed by regulating the number density of the ω phase below a threshold.

Background: We evaluated the significance of perinatal plasma natriuretic peptide (NP) levels in neonates with congenital heart defects (CHDs) or arrhythmias and determined whether measurement of perinatal plasma NP levels and echocardiographic assessment in utero could predict heart failure after birth., Methods: The study was conducted between 2012 and 2016 to evaluate the correlation of perinatal atrial NP (ANP) and brain NP (BNP) levels at birth with the modified Ross score after birth and the cardiovascular profile (CVP) score before birth., Results: A total of 122 singletons with CHDs or arrhythmias and 27 controls were analyzed. Neonatal blood sampling was performed at a median of 0.7 h (range, 0.1-1.5) after birth. The neonatal plasma ANP and BNP levels shortly after birth were significantly higher than those in the umbilical artery (UA) plasma. The ANP and BNP levels in UA and neonatal blood were correlated with the modified Ross score. The neonatal plasma ANP and BNP levels and the modified Ross scores were inversely correlated with the CVP score in neonates with CHDs or arrhythmias. The area under the receiver operating characteristic curve of UA ANP levels for predicting neonatal heart failure was highest among those for the CVP score, perinatal plasma ANP and BNP levels, and their combinations., Conclusions: The plasma ANP and BNP levels increased markedly shortly after birth. Assessment of the UA plasma ANP level at birth and the CVP score in utero may be utilized to predict neonatal heart failure., (© 2022 Japan Pediatric Society.)

A 62-year-old man was referred to our hospital for a lung tumor. Computed tomography (CT) of the chest showed a 62×55×68 mm well-circumscribed tumor in the upper lobe of the right lung. A transbronchial lung biopsy was performed, but a diagnosis was not achieved. Positron emission tomography-CT demonstrated intense F-fluorodeoxyglucose uptake in the mediastinal side of the tumor. Surgery was performed under the suspicion of primary lung cancer. The intraoperative pathological examination indicated a non-small-cell carcinoma. Thus, right upper lobectomy and wedge resection of the right lower lobe were performed. Microscopically, the tumor was composed of epithelial components, mimicking fetal lung tissue and embryogenic stroma. Therefore, the tumor was diagnosed as a biphasic pulmonary blastoma (p-StageⅡA). After the post-operative adjuvant chemotherapy, he has remained healthy without recurrence six years after the surgery.

Background: There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI)., Method and Results: Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24 h before and 3 h, 6 h, 1 day, and 2 days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1 day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1 day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1 day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner., Conclusions: Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients., (© 2021. Japanese Society of Nephrology.)

The requirements for biomedical materials have been raised greatly due to the rapidly aging global population. Shape memory alloys (SMAs) are indeed promising materials for biomedical applications due to their controllable shape deformation via the manipulation of temperature and/or stress. This study investigated the enhancement of the fundamental mechanical properties and the shape memory effect (SME) in the Ti-Cr-based alloys via the modification of Au and Cu. The quaternary Ti-Cr-Au-Cu alloys were successfully manufactured by physical metallurgy methods and their phase constitutions, mechanical properties, SME, and superelastic (SE) behaviors have been investigated in this study. Cold-workability, which was enhanced by the introduction of the Au element, was elaborated by the phase constitutions of the alloys. The β-parent phase was stabilized to around body temperature by the introduction of the β-stabilizers of Cr, Au, and Cu, and the functionalities of the specimens were revealed at the operating temperature. Perfect SME at the shape recovery rate of 100% was practiced by the substitution of Au by Cu and the mechanical properties, such as strength and ductility, were also enhanced. Functional mappings of the fundamental mechanical properties, which could be a helpful tool for the investigations of the quaternary Ti-Cr-Au-Cu alloys, were constructed in this work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Angiotensin II (Ang II) reportedly facilitates primary tumor growth and distal hematogenous metastasis formation in various murine intravenous metastasis models. However, it is unclear whether Ang II accelerates the initial processes of metastasis formation that begins in primary tumors surrounded by tumor microenvironment. We examined the effects of Ang II on primary tumors and lung metastasis lesions using a murine spontaneous metastasis model, in which triple negative breast cancer 4T1 cells constitutively expressing luciferase (4T1-Luc cells) were injected into the mammary fat pad of BALB/c mice. Subcutaneous injection of Ang II significantly accelerated primary tumor growth and lung metastasis formation. Ang II increased the protein expression levels of c-Myc, cyclin D1, fibronectin, vimentin, αSMA and Snail, and the treatment with the Ang II type 1 receptor blocker valsartan significantly suppressed the Ang II-induced increases of fibronectin and vimentin. Valsartan also significantly reduced lung metastatic lesions. However, Ang II did not have significant effects on 4T1-Luc cells including the proliferation, migration, invasion, or the expressions of proteins related to cell proliferation and epithelial-to-mesenchymal transition. In contrast, when 4T1-Luc cells were co-cultured with dermal fibroblasts, Ang II significantly accelerated cell migration and increased the expressions of fibronectin, vimentin, αSMA and Snail in 4T1-Luc cells. And moreover, Ang II significantly increased the mRNA expression of IL-6 in fibroblasts co-cultured with 4T1-Luc cells. These results suggested that Ang II accelerates surrounding fibroblasts by soluble factors such as IL-6 to promote epithelial-to-mesenchymal transition, which result in the initiation of cancer metastasis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Owing to the world population aging, biomedical materials, such as shape memory alloys (SMAs) have attracted much attention. The biocompatible Ti-Au-Ta SMAs, which also possess high X-ray contrast for the applications like guidewire utilized in surgery, were studied in this work. The alloys were successfully prepared by physical metallurgy techniques and the phase constituents, microstructures, chemical compositions, shape memory effect (SME), and superelasticity (SE) of the Ti-Au-Ta SMAs were also examined. The functionalities, such as SME, were revealed by the introduction of the third element Ta; in addition, obvious improvements of the alloy performances of the ternary Ti-Au-Ta alloys were confirmed while compared with that of the binary Ti-Au alloy. The Ti 3 Au intermetallic compound was both found crystallographically and metallographically in the Ti-4 at.% Au-30 at.% Ta alloy. The strength of the alloy was promoted by the precipitates of the Ti 3 Au intermetallic compound. The effects of the Ti 3 Au precipitates on the mechanical properties, SME, and SE were also investigated in this work. Slight shape recovery was found in the Ti-4 at.% Au-20 at.% Ta alloy during unloading of an externally applied stress.

Background: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients., Methods and results: In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%., Conclusions: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

With the development of new drugs, such as molecular-targeted drugs, and multidisciplinary therapies, cancer treatment outcomes have improved, and the number of cancer survivors is increasing every year. However, some chemotherapeutic agents cause cardiovascular complications (cancer treatment-related cardiovascular disease, CTRCVD), which affect the life prognosis and quality of life (QOL) of cancer patients. Therefore, it is necessary to select treatment methods that take into account the prognosis and QOL of cancer patients, and to take measures against CTRCVD. The mechanism of cardiotoxicity of high-risk drugs, such as doxorubicin and HER2 inhibitors, are still unclear; genetic factors, and cardiovascular disease risk factors (e.g., hypertension, dyslipidemia, and diabetes) are associated with CTRCVD progression. The establishment of methods for prevention, early diagnosis, and treatment of CTRCVD and the generation of evidence for these methods are needed. It is also necessary to develop screening methods for chemotherapy cardiotoxicity. In this review, we discuss the current status of CTRCVD, its complications, and expected countermeasures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To enhance the mechanical properties (e.g., strength and elongation) of the face-centered cubic (fcc) α-phase in the Au-Cu-Al system, this study focused on the introduction of the martensite phase (doubled B19 (DB19) crystal structure of Au 2 CuAl) via the manipulation of alloy compositions. Fundamental evaluations, such as microstructure observations, phase identifications, thermal analysis, tensile behavior examinations, and reflectance analysis, have been conducted. The presence of fcc annealing twins was observed in both the optical microscope (OM) and the scanning electron microscope (SEM) images. Both strength and elongation of the alloys were greatly promoted while the DB19 martensite phase was introduced into the alloys. Amongst all the prepared specimens, the 47Au41Cu12Al and the 44Au44Cu12Al alloys performed the optimized mechanical properties. The enhancement of strength and ductility in these two alloys was achieved while the stress plateau was observed during the tensile deformation. A plot of the ultimate tensile strength (UTS) against fracture strain was constructed to illustrate the effects of the introduction of the DB19 martensite phase on the mechanical properties of the alloys. Regardless of the manipulation of the alloy compositions and the introduction of the DB19 martensite phase, the reflectance stayed almost identical to pure Au.

Objectives: To evaluate the significance of natriuretic peptide (NP) levels in fetal arrhythmia., Study Design: Cardiovascular profile (CVP) scores and umbilical vein (UV) NP levels at birth were compared by different fetal arrhythmia statuses., Results: Fetal tachyarrhythmia ( n  = 22), bradyarrhythmia ( n  = 12), extrasystole ( n  = 12) and controls ( n  = 127) were enrolled in this study. Fetal antiarrhythmic therapy was performed in fetuses with tachyarrhythmia ( n  = 18) and bradyarrhythmia ( n  = 5). Fetal arrhythmias were divided into three groups: group A (arrhythmia controlled at birth, n  = 17), Group B (arrhythmia uncontrolled at birth, n  = 9) and Group C (fetal therapy not indicated, n  = 20). Group B had significantly lower CVP scores and higher NP levels than the other two groups and controls ( p  < .01). Groups A and C had significantly lower CVP scores than controls, but NP levels in Groups A and C showed no differences compared with controls., Conclusions: UV NP concentrations reflect the severity of fetal arrhythmia and responses to fetal therapy.

[Figure: see text].

Background & Aims: Nutritional metabolism is complex in pediatric patients with severe motor and intellectual disability (SMID), and therefore, appropriate estimation of the energy requirements is difficult. Focusing on ghrelin's role in energy metabolism regulation, we investigated plasma ghrelin levels in pediatric SMID patients and analyzed its nutritional significance as a regulatory marker of energy reserve., Methods: Fasting plasma total, acyl, and des-acyl ghrelin levels in 40 patients with SMID, including cerebral palsy (CP) (n = 20) and muscular disease (MD) (n = 8), and healthy controls (n = 13) were investigated. The correlations of plasma ghrelin levels with anthropometry, blood nutritional markers, energy intake, and resting energy expenditure (REE) measured with indirect calorimetry were analyzed. A p value < 0.05 was considered significant., Results: SMID patients had significantly higher acyl ghrelin, and lower body mass index (BMI), z-scores of body weight (BW), body height and BMI, and albumin than controls. CP patients had significantly higher total and acyl ghrelin, z-score of the mid-upper arm circumference (MUAC), retinol-binding protein, transthyretin, creatinine, and glucose than MD patients. Total and acyl ghrelin in CP patients and des-acyl ghrelin in MD patients had significant negative correlations with MUAC and upper arm fat area. In CP patients, total and acyl ghrelin had significant positive correlations with REE/BW (kcal/kg), and total ghrelin was predictive of REE/BW (r 2  = 0.625, p < 0.0001)., Conclusions: An increase in acyl ghrelin observed in SMID patients possibly indicates energy reserve deficiency. In CP patients, total and acyl ghrelin inversely reflected total body fat mass, resulting in strongly positive correlations with REE/BW. The measurement of plasma ghrelin may be useful to assess nutritional metabolism and energy reserve in pediatric SMID patients, such as CP and MD patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest associated with this manuscript., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Coronary computed tomography angiography (CCTA) non-invasively visualizes lipid-rich plaque. However, this ability is not fully validated in vivo. The current study aimed to elucidate the association of CCTA features with near-infrared spectroscopy-derived lipidic plaque measure in patients with coronary artery disease., Methods: 95 coronary lesions (culprit/non-culprit = 51/44) in 35 CAD subjects were evaluated by CCTA and NIRS imaging. CT density, positive remodeling, spotty calcification, napkin-ring sign and NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI 4mm ) were analyzed by two independent physicians. The association of CCTA-derived plaque features with maxLCBI 4mm  ≥ 400 was evaluated., Results: The median CT density and maxLCBI 4mm were 57.7 Hounsfield units (HU) and 304, respectively. CT density (r = -0.75, p < 0.001) and remodeling index (RI) (r = 0.58, p < 0.001) were significantly associated with maxLCBI 4mm , respectively. Although napkin-ring sign (p < 0.001) showed higher prevalence of maxLCBI 4mm  ≥ 400 than those without it, spotty calcification did not (p = 0.13). On multivariable analysis, CT density [odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.93-0.97; p < 0.001] and positive remodeling [OR = 7.71, 95%CI = 1.37-43.41, p = 0.02] independently predicted maxLCBI 4mm  ≥ 400. Receiver operating characteristic curve analysis demonstrated CT density <32.9 HU (AUC = 0.92, sensitivity = 85.7%, specificity = 91.7%) and RI ≥ 1.08 (AUC = 0.83, sensitivity = 74.3%, specificity = 85.0%) as optimal cut-off values of maxLCBI 4mm  ≥ 400. Of note, only 52.6% at lesions with one of these plaque features exhibited maxLCBI 4mm  ≥ 400, whereas the frequency of maxLCBI 4mm  ≥ 400 was highest at those with both features (88.5%, p < 0.001 for trend)., Conclusions: CT density <32.9 HU and RI ≥ 1.08 were associated with lipid-rich plaque on NIRS imaging. Our findings underscore the synergistic value of CT density and positive remodeling to detect lipid-rich plaque by CCTA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Vulnerable plaque features including lipidic plaque have been shown to affect fractional flow reserve (FFR). Given that formation and propagation of lipid plaque is accompanied by endothelial dysfunction which impairs vascular tone, the degree of lipidic burden may affect vasoreactivity during hyperemia, potentially leading to reduced FFR. Our aim is to elucidate the relationship of the extent of lipidic plaque burden with coronary physiological vasoreactivity measure., Methods: We analyzed 89 subjects requeuing PCI due to angiographically intermediate coronary stenosis with FFR ≤0.80. Near-infrared spectroscopy (NIRS) and intravascular ultrasound were used to evaluate lipid-core burden index (LCBI) and atheroma volume at both target lesion (maxLCBI 4mm ; maximum value of LCBI within any 4 mm segments) and entire target vessel (LCBI vessel : LCBI within entire vessel). In addition to FFR, delta-FFR was measured by difference of distal coronary artery pressure/aortic pressure (Pd/Pa) between baseline and hyperemic state., Results: The averaged FFR and delta-FFR was 0.74 (0.69-0.77), and 0.17±0.05, respectively. On target lesion-based analysis, maxLCBI 4mm was negatively correlated to FFR (ρ=-0.213, P=0.040), and it was positively correlated to delta-FFR (ρ=0.313, P=0.002). Furthermore, target vessel-based analysis demonstrated similar relationship of LCBI vessel with FFR (ρ=-0.302, P=0.003) and delta-FFR (ρ=0.369, P<0.001). Even after adjusting clinical characteristics and lesion/vessel features, delta-FFR (by 0.10 increase) was independently associated with maxLCBI 4mm (β=57.2, P=0.027) and LCBI vessel (β=24.8, P=0.007) by mixed linear model analyses., Conclusions: A greater amount of lipidic plaque burden at not only "target lesion" alone but "entire target vessel" was associated with a greater delta-FFR. The accumulation of lipidic plaque materials at both local site and entire vessel may impair hyperemia-induced vasoreactivity, which causes a reduced FFR., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: http://dx.doi.org/10.21037/cdt-20-1024). Kota Murai has received honoraria from Abbot, ZEON MEDICAL. Yu Kataoka serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from Jul 2019 to Jun 2021, and has received research support from Nipro and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda and Daiichi-Sankyo. The other author has no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Fetal heart failure is mainly caused by congenital heart defect and arrhythmia. It is difficult to appropriately diagnose the severity of fetal heart failure simply by ultrasonography because the development of a fetal heart in fetoplacental circulation and how well the fetal myocardium can adapt to postnatal cardiopulmonary circulation are challenging to assess. In adult cardiology, natriuretic peptides (NPs) are the most useful biomarker of heart failure; however, studies investigating NP levels in the fetuses and amniotic fluid are quite limited. Furthermore, little is known about their production and metabolism. This review summarized the most relevant findings on NP levels in the umbilical cord blood and amniotic fluid. The findings can then extend their use as a diagnostic biomarker of heart failure in fetuses with congenital heart defect and/or arrhythmia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miyoshi, Hosoda and Minamino.)

Objective: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation., Design: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP., Results: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test)., Conclusion: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Calcified nodule (CN) is an eruptive calcified mass causing acute coronary syndrome (ACS). Since coronary calcification is associated with an elevated cardiac event's risk, ACS attributable to CN may exhibit worse clinical outcome following percutaneous coronary intervention (PCI)., Methods: We retrospectively analyzed 657 ACS patients receiving PCI with newer-generation drug-eluting stent (DES) implantation under intravascular ultrasound (IVUS) guidance. CN was defined as (1) protruding calcification with its irregular surface and (2) the presence of calcification at adjacent proximal and distal segments. The primary endpoint was a composite of major adverse cardiac event [MACE = cardiac death + ACS recurrence + target lesion revascularization (TLR)]., Results: CN was identified in 5.3% (=35/657) of the study subjects. CN patients were more likely to have coronary risk factors including hypertension (p = 0.005), chronic kidney disease (p < 0.001), maintenance hemodialysis (p < 0.001) and a history of PCI (p < 0.001). During the observational period (median = 1304 days), CN was associated with an increased risk of MACE (HR = 7.68, 95%CI = 4.61-12.80, p < 0.001), ACS recurrence (HR = 12.32, 95%CI = 6.05-25.11, p < 0.001) and TLR (HR = 10.48, 95%CI = 5.80-18.94, p < 0.001). These cardiac risks related to CN were consistently observed by Cox proportional hazards model (MACE: p < 0.001, ACS recurrence: p < 0.001, TLR: p < 0.001) and a propensity score-matched cohort analysis (MACE: p = 0.002, ACS recurrence: p = 0.01, TLR: p = 0.005). Of note, over 80% of TLR at the CN lesion was driven by its re-appearance within the implanted DES., Conclusions: ACS patients attributable to CN have an increased risk of ACS recurrence and TLR, mainly driven by the continuous growth and protrusion of the calcified mass., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Percutaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is utilized for patients with cardiogenic shock or cardiac arrest. However, the procedure protocol for weaning from VA-ECMO has not been well established. The present study aimed to determine the usefulness of echocardiographic and pulmonary artery catheter parameters for predicting successful weaning from VA-ECMO in patients with refractory cardiogenic shock., Methods and Results: We retrospectively studied 50 patients who were hospitalized and supported by VA-ECMO for >48 h between January 2013 and March 2017. Patients successfully weaned from VA-ECMO without reintroduction of VA-ECMO or left ventricular assist device implantation were defined as 30 day survivors. Echocardiographic and pulmonary artery catheter parameters were evaluated when ECMO flow was limited to a maximum of 1.5-2.0 L/min. Twenty-four patients were successfully weaned from VA-ECMO, whereas 26 were not. Fractional shortening, corrected left ventricular ejection time (LVETc, defined as LVET divided by the square root of heart rate), left ventricular outflow tract velocity time integral, and LVETc divided by pulmonary artery wedge pressure (PAWP) were significantly larger in the 30 day survivor groups. Multivariable analysis revealed LVETc∕PAWP as a significant independent predictor of successful weaning (LVETc∕PAWP, odds ratio 0.82, 95% confidence interval 0.71-0.94, P = 0.005). Receiver operating characteristic curve analysis revealed 15.9 as the optimal LVETc∕PAWP for predicting successful weaning (area under the curve 0.82)., Conclusions: The present findings indicate that LVETc∕PAWP is a potential predictor of successful weaning from VA-ECMO., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Type 2 diabetes is a prominent risk factor for peripheral artery disease (PAD). Yet, the mechanistic link between diabetes and PAD remains unclear. This study proposes that dysregulation of the endogenous hormone ghrelin, a potent modulator of vascular function, underpins the causal link between diabetes and PAD. Moreover, this study aimed to demonstrate the therapeutic potential of exogenous ghrelin in a diabetic mouse model of PAD. Standard ELISA analysis was used to quantify and compare circulating levels of ghrelin between (i) human diabetic patients with or without PAD (clinic) and (ii) db/db diabetic and non-diabetic mice (lab). Db/db mice underwent unilateral hindlimb ischaemia (HLI) for 14 days and treated with or without exogenous ghrelin (150 µg/kg/day.) Subsequently vascular reparation, angiogenesis, hindlimb perfusion, structure and function were assessed using laser Doppler imaging, micro-CT, microangiography, and protein and micro-RNA (miRNA) analysis. We further examined hindlimb perfusion recovery of ghrelin KO mice to determine whether an impaired vascular response to HLI is linked to ghrelin dysregulation in diabetes. Patients with PAD, with or without diabetes, had significantly lower circulating levels of endogenous ghrelin, compared to healthy individuals. Diabetic db/db mice had ghrelin levels that were only 7% of non-diabetic mice. The vascular reparative capacity of diabetic db/db mice in response to HLI was impaired compared to non-diabetic mice and, importantly, comparable to ghrelin KO mice. Daily therapeutic treatment of db/db mice with ghrelin for 14 days post HLI, stimulated angiogenesis, and improved skeletal muscle architecture and cell survival, which was associated with an increase in pro-angiogenic miRNAs-126 and -132. These findings unmask an important role for endogenous ghrelin in vascular repair following limb ischemia, which appears to be downregulated in diabetic patients. Moreover, these results implicate exogenous ghrelin as a potential novel therapy to enhance perfusion in patients with lower limb PAD, especially in diabetics.

Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels using a statin is a cornerstone of preventive therapeutic management following acute myocardial infarction (AMI). In addition to its anti-atherosclerotic effects, recent studies reported a lower occurrence of heart failure (HF) under statin therapy. However, there is a wide variability in statin response. The association between the response to statin and the occurrence of HF in AMI subjects remains unclear. The purpose of present study is to examine whether the variability in statin response affects HF risk after AMI., Methods: We analyzed 505 statin-naïve AMI subjects undergoing primary percutaneous coronary intervention (PCI) who commenced atorvastatin, rosuvastatin, or pitavastatin. Statin hyporesponse was defined as a reduction in LDL-C levels <15% from baseline to 1 month after statin therapy. HF outcomes were compared between patients with and without statin hyporesponse., Results: Statin hyporesponse was identified in 15.2% (77/505) of study subjects. During a median 4.4-year observational period, statin hyporesponse was associated with a greater likelihood of HF [hazard ratio (HR) =3.01, 95% confidence interval (CI): 1.27-6.79, P=0.01]. This increased HF risk in statin hyporesponders was consistently observed in a multivariate Cox proportional hazards model (HR =2.74, 95% CI: 1.01-6.75, P=0.04), a propensity score-matched cohort (HR =12.30, 95% CI: 1.50-100.3, P=0.01) and in an inverse probability of treatment weights analysis with average treatment effects (coefficient =7.02, 95% CI: 2.29-21.58, P=0.0006)., Conclusions: Hyporesponse to statins increases HF risk after AMI. Our findings highlight statin hyporesponse as a high-risk feature associated with HF events., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-415). YK serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from Jul 2019 to Jun 2021. The other author has no conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

A 55-year-old man with esophageal cancer underwent esophagectomy along with lymph node dissection and reconstruction with gastric conduit through the sternal route. He developed a continuous cough with sputum production, 3 years postoperatively. Chest radiography revealed a right middle lung field infiltrate. Chest computed tomography revealed communication between the reconstructed esophagus and the gastric conduit( pull-up) and right middle lobe airways. Upper gastrointestinal examination revealed ulcerative lesions involving the gastric mucosa;however, biopsy of the ulcer showed no malignancy. Conservative therapy including fasting and proton-pump inhibitor administration did not improve symptoms caused by gastropleural fistula. Thoracotomy was performed through the anterolateral intercostal space under the right-up supine position, and the partial lung resection and direct closure of the stomach with muscle flap wrapping was performed.

In the original publication of this article [1] the wording of '3Di-PMR' was different between the text and figures.

Background: There is no established transplacental treatment for heart failure (HF) in utero, and no animal models or experimental systems of fetal HF have been established. This study aimed to investigate the effect of maternal tadalafil administration on fetal cardiovascular function and uteroplacental circulation in a murine model of fetal HF., Methods and Results: We first used an ultra-high-frequency ultrasound imaging system in utero and demonstrated that Hey2 -/- embryos had worsening right ventricular hypoplasia and marked left ventricular (LV) dilatation as gestation progressed. In both ventricles, fractional shortening (FS) and the E/A ratio were significantly lower in Hey2 -/- embryos than in wild-type embryos, indicating that the embryos can be used as a murine model of fetal HF. Subsequently, we evaluated the effect of tadalafil treatment (0.04 or 0.08 mg/ml; T0.04 or T0.08 groups, respectively) on fetoplacental circulation in Hey2 -/- embryos. LV FS was significantly higher in the T0.04 group than in control (P < 0.01), whereas LV dilation, mitral E/A ratio, and umbilical artery resistance index were not significantly different among all groups. The thinness of the LV compacted layer did not differ between the T0.04 and vehicle-treated Hey2 -/- embryos., Conclusions: A phenotype comprising marked dilatation and reduced FS of the left ventricles was identified in Hey2 -/- embryos, suggesting these embryos as a murine model of fetal HF. In addition, maternal administration of tadalafil improved LV systolic function without altering LV morphological abnormalities in Hey2 -/- embryos. Our findings suggest that tadalafil is a potential agent to treat impaired fetal ventricular systolic function., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Periprocedural myocardial injury (pMI) is a common complication of elective percutaneous coronary intervention (PCI) that reduces some of the beneficial effects of coronary revascularization and impacts the risk of cardiovascular events. We developed a 3-dimensional volumetric cardiovascular magnetic resonance (CMR) method to evaluate coronary high intensity plaques and investigated their association with pMI after elective PCI., Methods: Between October 2012 and October 2016, 141 patients with stable coronary artery disease underwent T1-weighted CMR imaging before PCI. A conventional 2-dimensional CMR plaque-to-myocardial signal intensity ratio (2D-PMR) and the newly developed 3-dimensional integral of PMR (3Di-PMR) were measured. 3Di-PMR was determined as the sum of PMRs above a threshold of > 1.0 for voxels in a target plaque. pMI was defined as high-sensitivity cardiac troponin T > 0.07 ng/mL., Results: pMI following PCI was observed in 46 patients (33%). 3Di-PMR was significantly higher in patients with pMI than those without pMI. The optimal 3Di-PMR cutoff value for predicting pMI was 51 PMR*mm 3 and the area under the receiver operating characteristic curve (0.753) was significantly greater than that for 2D-PMR (0.683, P = 0.015). 3Di-PMR was positively correlated with lipid volume (r = 0.449, P < 0.001) based on intravascular ultrasound. Stepwise multivariable analysis showed that 3Di-PMR ≥ 51 PMR*mm 3 and the presence of a side branch at the PCI target lesion site were significant predictors of pMI (odds ratio [OR], 11.9; 95% confidence interval [CI], 4.6-30.4, P < 0.001; and OR, 4.14; 95% CI, 1.6-11.1, P = 0.005, respectively)., Conclusions: 3Di-PMR coronary assessment facilitates risk stratification for pMI after elective PCI., Trial Registration: retrospectively registered.

Genomic DNA, which contains all of the genetic information, is damaged by a variety of endogenous and environmental factors such as genotoxic chemicals, ionizing radiation and UV light. Consequently, the DNA repair process is constantly active as it responds to damage in the DNA structure. Not only cardiotoxicity of anticancer drug treatment but also ischemic heart disease and heart failure associated with overloaded pressure interfere with DNA damage response and DNA repair regulation in cardiomyocytes. DNA methylation, catalyzed by the DNMTs, plays an important role in maintaining genome stability, but the molecular mechanism is not clear. In this study, we examine and outline the links between DNA methylation and the DNA damage repair systems and discuss the possible mechanisms of how they are orchestrated, with a focus on cardiotoxicity of anticancer drugs.