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There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. IL1B+ inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B+ inflammatory macrophages differentiated from S100A8/9/12+ classical monocytes uniquely observed in the aorta of AAD. We found increased infiltration of neutrophils and monocytes with the expression of inflammatory cytokines in the aorta and accumulation of inflammatory macrophages before the onset of macroscopic AAD in the murine AAD model. In blocking experiments using an anti-IL-1β antibody, it improved survival of murine AAD model by preventing elastin degradation. We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD. [ABSTRACT FROM AUTHOR]

The use of deicers in urban areas, on runways and aircrafts has raised concerns about their environmental impact. Understanding the ice-melting mechanism is crucial for developing environmentally friendly deicers, yet it remains challenging. This study employs machine learning to investigate the ice penetration capacity (IPC) of 21 salts and 16 organic solvents as deicers. Relationships between their IPC and various physical properties were analysed using extreme gradient boosting (XGBoost) and Shapley additive explanation (SHAP). Three key ice-melting mechanisms were identified: (1) freezing-point depression, (2) interactions between deicers and H2O molecules and (3) infiltration of ions into ice crystals. SHAP analysis revealed different ice-melting factors and mechanisms for salts and organic solvents, suggesting a potential advantage in combining the two. A mixture of propylene glycol (PG) and sodium formate demonstrated superior environmental impact and IPC. The PG and sodium formate mixture exhibited higher IPC when compared to six commercially available deicers, offering promise for sustainable deicing applications. This study provides valuable insights into the ice-melting process and proposes an effective, environmentally friendly deicer that combines the strengths of organic solvents and salts, paving the way for more sustainable practices in deicing. [ABSTRACT FROM AUTHOR]

Purpose: The present study analyzed the outcomes of our experience with abdominal aortic aneurysm (AAA) repair over 20 years using endovascular aortic repair (EVAR) with commercially available devices or open aortic repair (OAR) and reviewed our surgical strategy for AAA. Methods: From 1999 to 2019, 1077 patients (659 OAR, 418 EVAR) underwent AAA repair. The OAR and EVAR groups were compared retrospectively, and a propensity matching analysis was performed. Results: EVAR was first introduced in 2008. Our strategy was changed to an EVAR-first strategy in 2010. Beginning in 2018, this EVAR-first strategy was changed to an OAR-first strategy. After propensity matching, the overall survival in the OAR group was significantly better than that in the EVAR group at 10 years (p = 0.006). Two late deaths due to AAA rupture were identified in the EVAR group, although there were no significant differences between the OAR and EVAR groups with regard to the freedom from AAA-related death at 10 years. The rate of freedom from aortic events at 10 years was significantly higher in the OAR group than in the EVAR group (p < 0.0001). Conclusion: The rates of freedom from AAA-related death in both the OAR and EVAR groups were favorable, and the rate of freedom from aortic events was significantly lower in the EVAR group than in the OAR group. Close long-term follow-up after EVAR is mandatory. [ABSTRACT FROM AUTHOR]

This work implements artificial neural networks (ANNs) to monitor tool wear during turning of AISI D6 steel. The goal is to detect wear, prevent tool breakage, and enhance productivity. Experimental tests involve using polycrystalline cubic boron nitride tools to turn AISI D6 steel, measuring wear and surface roughness. ANNs are trained with machining forces, electric current, and acoustic emission data. Findings showed that cutting and machining forces, along with motor current, increased as the wear progresses. The dominant frequencies of the acoustic emission signal range from 30 to 40 kHz, with decreasing RMS as wear increases. The ANN achieved satisfactory results, with wear estimation deviations below 0.09 mm. However, its predictive capability beyond the training range is limited. Workpiece surface roughness estimation showed around 8% error compared to the experimental Ra values. Overall, the ANN-based approach enables real-time tool wear monitoring, reducing the risk of damage and optimizing productivity. [ABSTRACT FROM AUTHOR]

Introduction: An easy-to-use, multiuse, single-patient, electromechanical autoinjector, the SMARTCLIC®/CLICWISE® injection device, was recently developed to improve the self-administration options available to patients with chronic inflammatory disease treated with biologic agents. An extensive series of studies were conducted to guide the design and development of this device and to ensure its safety and effectiveness. Methods: Participants in two user preference studies and three formative human factor (HF) studies evaluated evolving iterations of the autoinjector device, dose dispenser cartridge, graphical user interface, and informational materials; participants in a summative HF test subsequently assessed the final proposed commercially representative product. In the user preference studies, rheumatologists and patients with chronic inflammatory disease, interviewed online and in-person, provided feedback on the design and functionality of four prototypes. In the HF studies, the safety, effectiveness, and usability of adapted prototypes were assessed under simulated-use conditions by patients with chronic inflammatory disease, caregivers, and healthcare professionals (HCPs). The safety and effectiveness of the final refined device and system were confirmed in a summative HF test by patients and HCPs in simulated-use scenarios. Results: Rheumatologists (n = 204) and patients (n = 39) interviewed in the two user preference studies provided feedback on the device size, feature ergonomics, and usability that guided prototype development in the subsequent formative HF studies. Observations from patients, caregivers, and HCPs (n = 55) participating in the latter studies yielded additional critical design revisions that culminated in development of the final device and system. Of 106 injection simulations conducted in the summative HF test, all resulted in successful medication delivery, and no potential harms were associated with injection-related use events. Conclusion: Findings from this research facilitated development of the SmartClic/ClicWise autoinjector device and demonstrated that it could be used safely and effectively by participants representative of the intended-use population of patients, lay caregivers, and HCPs. [ABSTRACT FROM AUTHOR]

The chemical and structural modification of organoborosilicate thin films was attempted by using alcohol-induced deboronation. A photocurable organoborosilicate was synthesized from 3-methacryloxypropyltrimethoxysilane and boric acid via a catalyst- and solvent-free and non-aqueous alcohol condensation process. The formation of Si-O-B linkage was suggested by 29Si NMR spectroscopy. A colorless and transparent thin film of the organoborosilicate was prepared by UV irradiation. According to Fourier transform infrared spectroscopy, a peak attributed to the stretching vibration of borate disappeared after the alcohol treatment. Moreover, atomic force microscopy revealed the surface structural change of the thin film via the deboronation process. These results indicate that the borate was eliminated by the treatment, suggesting that this method enables to apply to the direct nanofabrication. Highlights: A photocurable organoborosilicate was synthesized via catalyst- and solvent-free alcohol condensation. Borate was eliminated from the organoborosilicate thin film in the presence of methanol vapor. The thin film changed in chemical composition and structure due to methanol vapor treatment. The deboronation from organoborosilicate is expected to apply to a new type of nanofabrication. [ABSTRACT FROM AUTHOR]

Chiral inorganic materials have attracted increasing attention in the fields such as catalysis, electronics, photonics, and sensing. A new class of functional materials with chirality is extensively explored. Herein, we demonstrate the synthesis of nanometric nickel layered hydroxide salt (Ni-LHS) modified with chiral amino acids, (D- or L-) phenylalanine (PHE). An alkalization reaction in a starting mixture of nickel-phenylalanine aqua complexes was induced by using propylene oxide, leading to intercalate and adsorb phenylalanine on the surface and into the interlayers of Ni-LHS in an in-situ manner. The chiral molecules also act as surface modifier to inhibit the extensive crystal growth and aggregation, to form Ni-LHS with a diameter of 2–3 nm in a state of stablly-suspended in a solvent. It was also found that Ni-LHS exhibit induced circular dichroism (ICD) in the spectral range of d-d transitions of Ni(II) metal centres. The layered nanomaterials with chiroptical response demonstrated here is a promising option as an advanced adsorbent for detection of molecules. Highlights: Synthesis of nanometric nickel layered hydroxide salt accommodating chiral amino acids is achieved. Epoxide-mediated alkalization reaction is adopted for the synthesis of the stable sol of the nano hydroxide. The material is found to exhibit induced circular dichroism (ICD) in visible light range. [ABSTRACT FROM AUTHOR]

A more rapid and less complicated test to diagnose pertussis is required in clinical settings. We need to detect Bordetella pertussis, which mainly causes pertussis, as early as possible, because pertussis is more likely to become severe in infants, and people around them can easily become a source of infection due to its strong infectivity. Nevertheless, methods that can detect B. pertussis rapidly and efficiently are lacking. Therefore, we developed a new immunochromatographic antigen kit (ICkit) for the early diagnosis of pertussis. The ICkit detects B. pertussis antigens in a nasopharyngeal swab without equipment and provides the result in about 15 min with a simple procedure. Additionally, a prospective study to evaluate the ICkit was conducted in 11 medical institutions, involving 195 cases with suspected pertussis. Compared with the real-time polymerase chain reaction (rPCR), the sensitivity and specificity of the ICkit were 86.4% (19/22) and 97.1% (168/173), respectively. The ICkit detected the antigen in both children and adults. Furthermore, the ICkit detected the antigen until the 25th day from the onset of cough, when rPCR detected the antigen. Thus, the ICkit demonstrated a high correlation with rPCR and would help diagnose pertussis more rapidly and efficiently. [ABSTRACT FROM AUTHOR]

Assessment of frailty is important for risk stratification among the elderly with severe aortic stenosis (AS) when considering interventions such as surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). However, evidence of the impact of preoperative frailty on short-term postoperative outcomes or functional recovery is limited. This retrospective study included 234 consecutive patients with severe AS who underwent SAVR or TAVR at Kobe University Hospital between Dec 2013 and Dec 2019. Primary outcomes were postoperative complications, postoperative 6-min walking distance (6MWD), and home discharge rates. The mean age was 82 ± 6.6 years. There were 169 (SAVR: 80, TAVR: 89) and 65 (SAVR: 20, TAVR: 45) patients in the non-frail and frail groups, respectively (p = 0.02). The postoperative complication rates in the frail group were significantly higher than those in the non-frail group [30.8% (SAVR: 35.0%, TAVR: 28.9%) vs. 10.7% (SAVR: 15.0%, TAVR: 6.7%), p < 0.001]. The home discharge rate in the non-frail group was significantly higher than that in the frail group [85.2% (SAVR: 81.2%, TAVR: 88.8%) vs. 49.2% (SAVR: 55.0%, TAVR: 46.7%), p < 0.001]. The postoperative 6MWD in the non-frail group was significantly longer than that in the frail group [299.3 ± 87.8 m (SAVR: 321.9 ± 90.8 m, TAVR: 281.1 ± 81.3 m) vs. 141.9 ± 92.4 m (SAVR: 167.8 ± 92.5 m, TAVR: 131.6 ± 91.3 m), p < 0.001]. The TAVR group did not show a decrease in the 6MWD after intervention, regardless of frailty. We report for the first time that preoperative frailty was strongly associated with postoperative complications, 6MWD, and home discharge rates following both SAVR and TAVR. Preoperative frailty assessment may provide useful indications for planning better individualized therapeutic interventions and supporting comprehensive intensive care before and after interventions. [ABSTRACT FROM AUTHOR]

Molecular structures of siloxane materials should be highly controlled for achieving advanced functionalities. However, it is still difficult to precisely control the structure of siloxane materials by the sol–gel processing. In the present study, we focused on the silanol groups in the intermediate oligomers and resultant siloxane materials as a key structural unit for controlling the molecular structure. Thermal stability and chemical reactivity of silanol groups were found to be highly dependent on the steric effects of the surrounding side chains and siloxane skeletons. The present work suggests that controlling the steric effects around silanol groups in the intermediate oligomers allows modulating the crosslink density of siloxane skeletons. The selective molecular modification tunes the structure and chemical properties of the resultant siloxane materials. Highlights: Hydroxyl groups in oraganically modified siloxane oligomers exhibit a diffrent reactivity depending on the local environments. Molecular structures of siloxane materials should be highly controlled for achieving advanced functionalities. The selective molecular modification tunes the structure and chemical properties of the resultant siloxane materials. [ABSTRACT FROM AUTHOR]

Objectives: To review the outcomes of bicuspid aortic valve repair with the reimplantation technique. Patients and methods: From 2006 to 2018, 46 patients with bicuspid aortic valve underwent the reimplantation procedure for aortic valve repair. Those patients were included in this study. The mean age was 45 ± 15 years and 44 were male. Preoperative echocardiography showed a mean ventriculoaortic junction diameter of 28 ± 3 mm. The mean diameter at the sinus of Valsalva was 41 ± 9 mm. The minimum cusp height was 19 ± 3 mm. Regarding cusp repair technique, central plication was used in 45 patients, free margin reinforcement in 10 patients, and patch repair in 4 patients. Follow-up was performed by annual echocardiography. Results: There were no hospital deaths. All patients were found with either no/trivial or mild AR on postoperative transesophageal echocardiography. The postoperative ventriculoaortic junction diameter was 23 ± 2 mm and 83 ± 17% preoperatively. Freedom from moderate AR was 85 ± 6% at 5 years, and freedom from reoperation was 93 ± 4% at 5 years. Conclusions: Reimplantation for bicuspid aortic valve repair showed acceptable mid-term outcomes. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect "heart regeneration", replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the mid-term outcomes of transarterial embolization (TAE) for type II endoleak after endovascular abdominal aortic aneurysm repair (EVAR) and investigate the predictors of sac enlargement after embolization.Materials and Methods: We conducted a retrospective analysis of 55 patients [48 men and 7 women, median age 79.0 (interquartile ranges 74-82) years] who underwent TAE for type II endoleak from 2010 to 2018. The aneurysmal sac enlargement, endoleaks, aneurysm-related adverse event rate, and reintervention rate were evaluated. Patients' characteristics and clinical factors were evaluated for their association with sac enlargement.Results: Fifty-five patients underwent TAE with technical success and were subsequently followed for a median of 636 (interquartile ranges 446-1292) days. The freedom from sac enlargement rates at 1, 3, and 5 years was 73.2%, 32.0%, and 26.7%, respectively. After initial TAE, the recurrent type II, delayed type I, and occult type III endoleak were identified in 39 (71%), 5 (9%), and 3 (5%) patients, respectively. Although a patient had aorto-duodenal fistula, there was no aneurysm-related death. The freedom from reintervention rates was 84.6%, 35.7%, and 17.0%, respectively. In the multivariate analysis, sac diameter > 55 mm at initial TAE (hazard ratios, 3.23; 95% confidence intervals, 1.22-8.58; P < 0.05) was a significant predictor of sac enlargement.Conclusion: TAE for type II endoleak was not effective in preventing sac enlargement, and reinterventions were required among the mid-term follow-up. The sac diameter > 55 mm at initial TAE was a significant predictor of sac enlargement. [ABSTRACT FROM AUTHOR]

There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. Cattle heart protein hydrolysate ultra-filtrate (HPHU, molecular weight < ca. 1,000 Da peptide mixture) exhibits cholesterol-lowering activity in hypercholesterolemic rats, but the active peptide in HPHU that lowers serum cholesterol levels and its molecular mechanism are unknown. In this study, we separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. We identified FP as an active peptide from HPHU by MALDI-TOF mass spectrometry. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. FP significantly increased serum HDL cholesterol, accompanied by a significant decrease in the atherogenic index. FP also significantly increased fecal cholesterol and acidic steroid excretion. Moreover, FP significantly decreased ATP-binding cassette transporter A1 (ABCA1) expression in the rat jejunum and reduced cholesterol absorption in Caco-2 cells. We found a novel cholesterol-lowering dipeptide FP that could improve cholesterol metabolism via the down-regulation of intestinal ABCA1. The cholesterol-lowering action induced by FP was disappeared in PepT1KO mice. FP-induced cholesterol-lowering action is mediated via PepT1 in mice. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to elucidate the outcomes after surgical resection of Masaoka stage III-IV thymic epithelial tumors.Methods: We retrospectively reviewed patients with Masaoka stage III-IV thymic epithelial tumor who underwent surgical resection from January 1995 to January 2017. The clinicopathological features, surgical procedures, and postoperative outcomes were investigated.Results: Thirteen patients with thymoma and 18 patients with thymic carcinoma were assessed. The postoperative Masaoka stages were III/IVa/IVb = 8/4/1 in thymoma and III/IVa/IVb = 11/2/5 in thymic carcinoma. In patients with thymoma, the World Health Organization pathological subtypes were A/B1/B2/B3 = 2/1/4/6. We performed combined resection and reconstruction for brachiocephalic vein or superior vena cava in 3 patients with thymoma and 7 patients with thymic carcinoma. In all patients, the patency rate of the grafts was very low for the left brachiocephalic vein and well maintained for the right brachiocephalic vein. Macroscopically and pathologically complete resection was achieved in 11 and 6 patients with thymoma, respectively, and in 15 and 9 patients with thymic carcinoma, respectively. The 10-year survival rates were 85.7% in thymoma and 70.3% in thymic carcinoma. Postoperative recurrences were observed in 2 and 9 patients with thymoma and thymic carcinoma, respectively. Recurrences were observed within 5 and 10 years after surgery in 2 patients with thymoma and within 2 years in all patients with thymic carcinoma.Conclusions: Patients with Masaoka stage III-IV thymic epithelial tumor showed relatively favorable long-term survival after surgical treatment. Therefore, aggressive surgical resection for complete resection may be a treatment option for these conditions. [ABSTRACT FROM AUTHOR]

A 67-year-old man consulted our department with gross hematuria. Computed tomography (CT) revealed a huge renal tumor with a paracaval metastatic lymph node (mLN). Right total nephrectomy was planned for the renal tumor diagnosed as renal cell carcinoma preoperatively. Just before the resection of the renal vein and artery, intraoperative ultrasonography revealed an inferior vena caval tumor thrombus (IVCTT) extending from the mLN. Ultrasonography clearly and dynamically demonstrated a rhythmic flapping movement of the IVCTT with blood flow in the inferior vena cava. Following right radical nephrectomy, IVCTT resection with the vessel wall was performed to reduce the risk of pulmonary tumor thrombus. Histopathological diagnosis of the renal tumor was clear cell renal cell carcinoma, and the resected IVCTT was confirmed histopathologically as tumor involvement from the mLN of the renal cell carcinoma. Intraoperative ultrasonography can detect IVCTT extending from the mLN, whereas CT cannot. [ABSTRACT FROM AUTHOR]

We experienced a case of ventricular assist with both a pulsatile-flow and a continuous-flow pump in a pediatric patient, and herein report the clinical course and characteristics of the pumps. A 6-year-old female was diagnosed with fulminant myocarditis and transferred to our hospital for mechanical support. After 12 days of extracorporeal membrane oxygenation, we implanted a left ventricular assist device (LVAD) and a right ventricular assist device (RVAD) using centrifugal Gyro pumps with a membrane oxygenator in a paracorporeal fashion. The membrane oxygenator was removed on postoperative day (POD) 4, and the patient was weaned from the respirator on POD 6. The LVAD was exchanged on POD 13 and 17, and the RVAD was exchanged on POD 14 because of thrombus formation inside the pumps. The RVAD was removed on POD 25. On POD 32, the patient experienced cerebral infarction and the centrifugal Gyro pump was switched to an extracorporeal pulsatile pump. No thromboembolic event occurred after pump conversion, although continuous administration of vasodilators was required to avoid hypertension. She underwent successfully heart transplantation in the USA after 8 months of ventricular support. A centrifugal pump is considered useful for pediatric patients, as pump flow and blood pressure can be relatively easily controlled in the postoperative acute phase compared with the pulsatile pump. However, special care should be taken to monitor for thrombus formation when support length becomes longer than 13 days, and a switch to a pulsatile pump should be considered once the hemodynamic status stabilizes. [ABSTRACT FROM AUTHOR]

Influenza is a widespread disease caused by infection with the influenza virus. Vaccination is considered to be the main countermeasure against influenza. A split vaccine is widely used to avoid severe adverse events, and it induces strong humoral immunity. However, the split vaccine alone cannot elicit mucosal immunity, including IgA production, and its preventative effects are limited. Here, we show that the green tea cultivar 'Benifuuki' extract enhanced the effect of a split vaccine on mucosal immunity. The frequency of IgA cells was increased in lung and Peyer's patch that received Benifuuki diet. Secretion of hemagglutinin-specific mucosal IgA, which is closely linked to the prevention of viral infection, was significantly increased in the bronchoalveolar lavage fluid of split vaccine-immunized BALB/c mice that were administered green tea Benifuuki extract. Our findings suggest that Benifuuki intake enhanced the effects of the split vaccine on mucosal immunity. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the protective effect of glucagon-like peptide 1 (GLP-1) signaling on the cardiovascular system, we conducted this study to show that the GLP-1 receptor analog (lixisenatide) could inhibit abdominal aortic aneurysm (AAA) development in rats. Methods: Lixisenatide was injected subcutaneously 7 days after aneurysm preparation. We evaluated reactive oxygen species (ROS) expression by dihydroethidium staining and 8-hydroxydeoxyguanosine (8-OHdG; the oxidation product of DNA) by immunohistochemical staining. We also analyzed the effect of GLP-1 signaling on the inflammatory response. Histopathological examination was done on day 28, and the AAA dilatation ratio was calculated. Results: On day 14, ROS expression and 8-OHdG-positive cells in the aneurysm walls were seen to have been significantly decreased by lixisenatide treatment. Western blot analysis showed decreased ERK expression. There was significantly reduced tumor necrosis factor-α mRNA expression in the aneurysm walls and CD68-positive cell infiltration in the aneurysm walls. On day 28, it was evident that the lixisenatide had dramatically reduced aneurysm development in the rats. Conclusion: GLP-1 elevation inhibits AAA development in rats through its anti-oxidant and anti-inflammatory effects. Thus, GLP-1 could be a potent pharmacological target for AAA treatment. [ABSTRACT FROM AUTHOR]

A superhydrophobic adhesive surface is applied to titanate nanotube (TNT) brushes through surface modification using capric acid. Hydroxyl groups on the TNT brushes are reacted with carboxylic acids via esterification using a chemical vapor deposition method at 110 °C. The alignment of the titanate nanostructures and the surface modification with capric acid resulted in a hydrophobic surface. The hydrophobicity increases with surface modification time; the contact angle, θ , increases from 0° to 152°. After 4 h modification, the surface shows superhydrophobicity with water adhesion ability. The use of carboxylic acids as modifiers offers advantages that include low cost, environmental compatibility, and non-toxicity and is capable of adapting TNT-based functional interfaces toward a variety of applications. Graphical Abstract: [ABSTRACT FROM AUTHOR]

UDP-glucuronosyltransferase 1A9 (UGT1A9) contributes to the glucuronidation of numerous drugs. Cynomolgus monkeys are regarded as experimental animals similar to humans in studies on safety evaluation and biotransformation for drug development. In this study, the similarities and differences in the enzymatic properties of UGT1A9 between humans and cynomolgus monkeys were precisely identified. UGT1A9 cDNAs of humans (humUGT1A9) and cynomolgus monkeys (monUGT1A9) were cloned, and the corresponding proteins were heterologously expressed in Sf9 cells. The enzymatic properties of UGT1A9s were characterized by kinetic analysis of propofol glucuronidation. The amino acid homology between humUGT1A9 and monUGT1A9 was 93.2 %. Propofol glucuronidation by recombinant humUGT1A9 and monUGT1A9 exhibited substrate inhibition and monophasic Michaelis-Menten kinetics, respectively. The K, V and CL values of humUGT1A9 were 15.0 μM, 1.56 nmon/min/mg protein and 107 μL/min/mg protein, respectively. The K value of monUGT1A9 was 8.8-fold higher than humUGT1A9, and the V and CL values of monUGT1A9 were 15 and 2 % of humUGT1A9, respectively. These findings suggest that the enzymatic properties of UGT1A9 are considerably different between humans and cynomolgus monkeys, although humUGT1A9 and monUGT1A9 were highly conserved at the amino acid level. The information on species differences in UGT1A9 function gained in this study should help with the in vivo extrapolation of drug metabolism. [ABSTRACT FROM AUTHOR]

A 30-year-old man with Marfan syndrome who underwent Crawford type II extension aneurysm repair about 9 years ago was referred to our hospital with persistent fever. Computed tomography (CT) showed air around the mid-descending aortic prosthetic graft. Because the air did not disappear in spite of intravenous antibiotics, F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was performed. FDG-PET/CT revealed four high-uptake lesions. After dissecting the aortic graft particularly focusing on the high-uptake lesions, this patient underwent in situ graft re-replacement of descending aortic graft with a rifampicin-bonded gelatin-impregnated Dacron graft and omentopexy. The patient remains well without recurrent infection at 3 months after surgery. [ABSTRACT FROM AUTHOR]

Midsternotomy in patients with a coexisting tracheostomy is associated with a risk of deep sternal wound infection (DSWI) or mediastinitis. We herein present two cases of total arch replacement using a surgical technique designed to avoid the danger of DSWI. Total arch replacement via an antero-lateral thoracotomy with partial sternotomy can be one of the options for patients with a tracheostoma or after laryngectomy, and can both protect organs and avoid DSWI. [ABSTRACT FROM AUTHOR]

Secundum atrial septal defect (ASD) is the most common form of congenital heart disease in adults. Surgical and transcatheter closures of ASD are widely accepted therapeutic approaches. In patients with severe pulmonary arterial hypertension (PAH), however, the closure of the defect is still controversial. We report two cases of ASD patients with severe PAH successfully repaired subsequent to effective medical therapy. Subsequent shunt closure after targeted medical therapy can be an effective strategy in selected ASD patients with severe PAH. [ABSTRACT FROM AUTHOR]

Objectives: To improve the clinical outcome of patients with severe functional mitral regurgitation (FMR) associated with ischemic cardiomyopathy (ICM), we compared the therapeutic efficacy of mitral annuloplasty (MAP) with that of mitral valve replacement (MVR). Methods: In a retrospective observation 63 consecutive patients underwent mitral valve surgery for severe ICM-FMR from November 1999 to March 2012. All patients had severe FMR (regurgitant volume >60 ml/beat) with Carpentier type I and type IIIb disease. Mean RV was 74.0 ± 35.0 ml/beat and coaptation depth was 12.7 ± 3.0 mm. Twenty-six patients (41.3 %) were treated by MVR with sparing of the subvalvular apparatus and 37 (58.7 %) by MAP. Results: Total in-hospital mortality was 6.3 %. Kaplan-Meier survival estimates at 1 and 5 years were 84.2 and 78.6 % in the MVR group and 82.6 and 71.6 % in the MAP group, with no significant difference between groups ( p = 0.758). Freedom from major adverse cardiac and cerebrovascular events (MACCE) at 5 years was 66.9 % for patients treated by MVR and 64.1 % for those treated by MAP ( p = 0.866). At the last follow-up visit, >grade II MR had recurred in 4 annuloplasty patients (10.8 %). In multivariate analysis, independent predictors of increased late death and MACCE were significantly associated with residual pulmonary hypertension (late death: odds ratio = 25.0, p = 0.0009; MACCE: odds ratio = 31.3, p = 0.0001). Conclusions: Mitral valve replacement with sparing of the subvalvular apparatus is a safe and effective surgical alternative for patients with severe FMR. [ABSTRACT FROM AUTHOR]

The article discusses the practice guidelines which review the factors influencing the voriconazole (VRCZ) pharmacokinetic profile conducted by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring (JSTDM). It examines the data that support exposure-toxicity and exposure-effect relationships that cause difficulty for therapeutic drug monitoring for VRCZ. It also mentions indications for VRCZ therapeutic drug monitoring (TDM).

The article discusses the guidelines for drug monitoring (TDM) of vancomycin (VCM) and the reviews for TDM by Japanese Society of Therapeutic Drug Monitoring (JSTDM) and Japanese Society of Chemotherapy (JSC). It says that the guidelines for TDM of VCM were reviewed by the practice guidelines committee. It states that the TDM and VCM dosing recommendations were not stated in the guidelines for patients undergoing continuous renal replacement therapy (CRRT) and with renal function deterioration.

Delayed diagnosis or surgery sometimes causes more extensive destruction of aortic periannular abscess, or pseudoaneurysm, resulting in left ventricular-aortic discontinuity, particularly in patients with prosthetic valve endocarditis. The condition complicates the surgical procedures and causes worsening of short- and long-term outcomes. In-hospital mortality in patients with prosthetic valve endocarditis has been reported to be as high as 15-20 %, even at leading hospitals in the world. Contemporary modes of surgery for periannular abscess/pseudoaneurysm involve drainage of the cavity, radical debridement of necrotic tissue, annular reconstruction of the destroyed annulus, and root replacement using an optimal conduit. Radical debridement is of primary importance and is the universally accepted procedure, which frequently requires annular reconstruction using a pericardial patch. Conventional aortic valve replacement using a mechanical or stented biological valve, aortic valve replacement with translocation, aortic root replacement using an allograft, pulmonary autograft (Ross procedure), stentless biological valve, or a composite graft are conduits of choice. All things considered, allograft is believed to be the best conduit for a destroyed annulus because of better fit and its resistance to infection; however, recent reports have failed to confirm the superiority of allograft over other conduits in terms of long-term survival and freedom from reoperation/recurrence of infection. Short- and long-term outcomes have been studies for every type of conduit, but the selection of conduits for aortic root replacement is still controversial. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac surgery for the patients with advanced liver cirrhosis is still challenging. High mortality has been reported in the literature. We evaluate the clinical outcome of cardiac surgery in patients with advanced liver cirrhosis. Methods: Patients with advanced liver cirrhosis who underwent cardiac surgery between October 1999 and April 2009 were reviewed. The severity of liver cirrhosis was assessed using Child-Pugh class, Child-Pugh score, and MELD score. Advanced liver cirrhosis was defined as Child-Pugh class B or C. Cardiopulmonary bypass (CPB) was carried out at higher flow rate (2.4-3.2 L/min/m), and hematocrit (25-30 %). Moderate and more tricuspid regurgitation were aggressively treated. Dilutional ultrafiltration was performed at the termination of CPB. Results: Eighteen patients (mean age 70 years, male:female = 14:4) were identified. Twelve patients had hepatitis virus infection and 6 cases were alcohol-related. Fourteen patients were graded as Child-Pugh class B and 4 in class C. Seventeen patients underwent cardiac surgery with the use of cardiopulmonary bypass, and 1 patient underwent off-pump coronary artery bypass surgery. The overall mortality rate was 17 % (3 of 18). The cause of death was liver failure, esophageal variceal bleeding and bacteremia. The mortality of redo surgery was high (50 %). The incidence of postoperative liver failure was 11 % (2 of 18). Child-Pugh class or score was not correlated with hospital mortality. MELD score was significantly higher in hospital mortality (10.8 ± 4.0 vs. 17.3 ± 2.1, p = 0.001). Conclusions: Although the mortality of redo surgery was high, cardiac surgery could be safely performed in selected patients with advanced liver cirrhosis. [ABSTRACT FROM AUTHOR]

Synthesis of titanate nanotubes (TNTs) from sol-gel derived amorphous TiO thin films under moderate hydrothermal condition has been reported. TNTs from film possess a tubular morphology that is the same crystalline phase as one synthesized from TiO powder so far. TNTs obtained in this study are not entangled one another but oriented and isolated on the substrate. Growth of highly oriented TNTs is observed in micro grooves of amorphous TiO thin film. Their orientation is also maintained with the growth of TNTs. [ABSTRACT FROM AUTHOR]

Intra-articular loose bodies (ILBs) are not uncommon conditions in patients with various joint diseases. Their morphological alterations have been investigated in detail, but little attention has been paid to their fatty lesions. In this study, we examined fatty bone marrow, fat cells without bone marrow structures (extramedullary fat cells), and their necrotic changes in 55 ILBs surgically removed from 42 patients, excluding primary synovial chondromatosis cases. The presence of viable re-vascularized vessels with or without enchondral ossification could discriminate 19 re-attached ILBs from 36 true free ILBs. Fatty bone marrow was found in 25 ILBs, and its necrosis was recognized in 11 (44.0%) of them. Extramedullary fat cells, characterized by single or clustered fat cells focally or multifocally distributed in fibrous or cartilaginous stroma, were identified in seven true free ILBs (7of 55, 12.7%), and all of them were focally necrotic. Unique lipomembranous changes were detected in 7 (12.7%) of 55 ILBs; they were found in 4 (36.4%) of 11 ILBs of necrotic bone marrow and were associated with 3 (42.9%) of 7 necrotic extramedullary fatty lesions. These changes were highlighted by periodic-acid Schiff and Masson's trichrome stain more clearly. We concluded that extramedullary fat cells represent lipometaplasia in ILBs with no blood supply. We considered that lipomembranous changes in ILBs can be a useful hallmark for necrotic bone marrow or necrosis of extramedullary lipometaplastic lesions. [ABSTRACT FROM AUTHOR]

72-year-old woman with a known history of homozygous familial hyperlipidemia (IIa) was referred to our hospital for an operation necessitated by aortic and mitral stenosis and paroxysmal atrial fibrillation. Computed tomography and cardiac catheterization revealed a heavily calcified aortic root and mitral annulus as well as a high-grade stenosis of the left anterior descending and right coronary arteries. Double aortic and mitral valve replacement concomitant with replacement of ascending aorta, maze III procedure, and coronary artery bypass were performed. Temporary hypothermic arrest was employed to reduce the risk of cerebral emboli. [ABSTRACT FROM AUTHOR]

Aortoesophageal fistula is a fatal disease which needs immediate control of bleeding and infection. We report a case of aortoesophageal fistula successfully treated with extra-anatomical bypass and complete resection of infected aorta and esophagus following endovascular repair. He was discharged after reconstruction of esophagus and recurrence of infection has not been observed for the past 5 years. [ABSTRACT FROM AUTHOR]

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were fortified at a level of 1.5% in a composed diet. The effects were confirmed in 0-year black sea bream Acanthopagrus schlegeli in terms of lipid metabolism and physiological activity. The EPA group was high in EPA in muscle, liver, intraperitoneal fat body (IPF), eye and brain. The levels of DHA in liver, eye, brain and heart were also high in the EPA group, suggesting that conversion of EPA to DHA occurred in those organs. Fortification of DHA increased the levels of DHA in organs except the eye, but did not affect EPA levels. Both the EPA and DHA groups showed smaller adipocytes or lower levels of lipid content than the control group. The starvation followed by feeding experiment caused marked body weight loss in the control group by consumption of muscle protein and lipids in IPF. Fortifications of EPA and DHA induced less mobilization of muscle protein and IPF lipids as energy. Liver function and resistance to air-dipping were improved by both EPA and DHA fortifications. The present results implied conversion of EPA to DHA in the fish with regard to parameters, such as lipid metabolism and physiological vitality. [ABSTRACT FROM AUTHOR]

ABSTRACT: Hatchery-reared black sea bream Acanthopagrus schlegeli juveniles averaging 0.05 g in body weight were fed either a control diet (commercial diet) or an experimental diet in which the commercial diet was fortified with 50 mg l-ascorbyl 2-monophosphate Mg (APM)/100 g diet for 50 days. Calcium ascorbate supplemented as a vitamin mixture in the control diet was completely destroyed during storage. Fortification with APM significantly increased the ascorbic acid levels in the muscle, liver, brain and eye. Although APM fortification did not influence growth, survival or fish body composition, adipocyte diameter in the intraperitoneal fat body (IPF) was significantly reduced. After the feeding experiment, the fish were kept for 39 days without feeding. Fortification with APM resulted in high survival, high muscle protein retention and low body weight loss. The results suggested the necessity of fortification with an adequate amount of ascorbate in the diet. While fatty acid compositions of the IPF, muscle and liver were not significantly influenced by APM fortification, characteristic changes in the fatty acid profile were found after starvation. Vitamin C and highly unsaturated fatty acids seemed crossly interactive in relation to lipolysis activity in black sea bream juveniles. [ABSTRACT FROM AUTHOR]

A 59-year-old man was admitted with general fatigue, an epigastric mass, and remittent fever. Radiological examinations disclosed a huge solid-to-cystic mass in the right lobe of the liver, and the mass severely compressed the right diaphragm, the inferior vena cava, and the right atrium. In addition, the patient suffered from chronic hepatitis; however, the serum α-fetoprotein, carcinoembryonic antigen, and PIVKA II levels were all within the normal ranges. The serum C-reactive protein level was 7.71 mg/dl. With a clinical diagnosis of a malignant hepatic tumor invading the right diaphragm, surgery was performed. The tumor originated from segments IV and VII of the liver, was well defined, and grew extrahepatically. The tumor was resected using an ultrasonic cavitational aspirator together with the infiltrated right diaphragm. The resected tumor measured 23 × 13 × 23 cm in size and weighed 3 700 g. Histologically, the tumor was found to consist of hepatocellular carcinomatous component and sarcomatous component. In the sarcomatous component, spindle-shaped cells which were positive for the immunohistochemical localization of vimentin, α-smooth muscle actin, and keratin were identified. The postoperative course was uneventful. The value of the serum C-reactive protein returned to within the normal range, and the patient became afebrile. The patient received a postoperative combination chemotherapy (etoposide, epirubicin, and cisplatin), and remains well with no signs of recurrence 12 months after the operation. [ABSTRACT FROM AUTHOR]

Objective: Cytokine induction can occur routinely in cardiac surgery with cardiopulmonary bypass. We have studied the relationships between the kinetics of pro-inflammatory cytokine release and the postoperative organ function. Methods: Ten adult patients (6 men and 4 women) undergoing elective cardiac surgery with cardiopulmonary bypass, at Hiroshima University Hospital were studied. Patients with acute infection, insulin-dependent diabetes, acute or chronic respiratory failure, renal or hepatic failure, acute cardiogenic shock, and emergency patients were not included. The age of the patient ranged from 44 to 78 years (mean 69±2.0 years). The type of surgical intervention performed was coronary artery bypass grafting in four patients, mitral valve plasty or replacement with modified maze procedure in another five patients, and both procedures in the other one patient. Plasma cytokine levels until 48 hours after aortic declamping were measured in blood samples. The Respiratory Index and the serum levels of choline esterase and creatinine were also measured. The plasma levels of the pro-inflammatory cytokines (interleukin-6 and interleukin-8) were measured. Results: The highest interleukin-6 levels were significantly correlated with hepatic dysfunction (r=−0.80, p=0.0) and with renal dysfunction (r=0.78, p=0.009). The highest interleukin-8 levels were significantly correlated with respiratory dysfunction (r=0.86, p=0.001). Conclusion: The highest proinflammatory cytokines levels at 1 hour after aortic declamping were related to damage to postoperative organ functions, involving the lung, kidney and liver. [ABSTRACT FROM AUTHOR]

Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion receptor, procoagulant and permeability-related genes are coordinately upregulated by rapid ischemia-mediated activation of Egr-1. Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion, and enhanced animal survival and organ function. Rapid activation of Egr-1 in response to oxygen deprivation primes the vasculature for dysfunction manifest during reperfusion. These studies define a central and unifying role for Egr-1 activation in the pathogenesis of ischemic tissue damage. [ABSTRACT FROM AUTHOR]

A novel method for determining mode power distribution in a two-mode fiber illuminated by an offset beam by measuring the near field pattern on the test fiber endface is developed. This method utilizes the different field symmetries of the fundamental and the second order modes. Coupling efficiencies from a quasi Gaussian beam to the fundamental and the second order modes in a two mode fiber were measured by the new technique for various offset launching conditions, and were in good agreement with the theoretical ones. [ABSTRACT FROM AUTHOR]

Successful repair of a distal aortic arch aneurysm without aortic cross-clamping was carried out in a 74-year-old man, using a combination of special separate cerebral perfusion and retrograde coronary perfusion, termed non-clamping selective cerebral perfusion. We believe that satisfactory results following aortic arch surgery in elderly patients can only be achieved through the prevention of emboli derived from an aortic cross-clamping site, and shortened ischemic time of the vital organs. [ABSTRACT FROM AUTHOR]

Dextrocardia associated with situs inversus totalis is a rare condition. A small number of patients with the condition have been reported after undergoing myocardial revascularization. We experienced a case of this rare disorder in an 83-year-old man. He was successfully treated by off-pump coronary artery bypass grafting with bilateral internal thoracic arteries and a saphenous vein. Except for the mirror-image anatomy, the surgical technique was similar to that used for a patient with situs solitus. [ABSTRACT FROM AUTHOR]

A 39-year-old woman with familial homozygous hypercholesterolemia had supravalvular and valvular aortic stenosis. Modified Nick's procedure and aortic valve replacement was performed to relieve both the supravalvular and annular stenoses. At surgery, the ascending aorta was found to be narrowing at the level of the sinotubular junction, which was compatible with congenital supravalvular aortic stenosis. Histological examination of the aortic cusps showed sclerotic change due to hypercholesterolemia. These findings indicated that familial homozygous hypercholesterolemia caused valvular aortic stenosis and exacerbated congenital supravalvular aortic stenosis. [ABSTRACT FROM AUTHOR]

We report a rare case of isolated pulmonary stenosis in a 66-year-old woman. The patient underwent successful pulmonary valve replacement with a stentless bioprosthetic valve. The pulmonary valve was exposed with a longitudinal incision from the right ventricular outflow tract to the pulmonary trunk. The proximal posterior part of the bioprosthetic valve was anastomosed to the pulmonary valve annulus and the distal side was anastomosed to the pulmonary artery with an inclusion technique. The defect from the pulmonary artery to the right ventricular outflow tract was closed using an equine pericardium patch. The patient had an uneventful postoperative course. [ABSTRACT FROM AUTHOR]

A 61-year-old man developed a ruptured innominate artery associated with localized acute dissection. The innominate artery was reconstructed with a bifurcated prosthetic graft without brain complication. [ABSTRACT FROM AUTHOR]

Unicuspid aortic valve is a rare congenital cardiac abnormality, leading to aortic stenosis or regurgitation. We report the case of a 55-year-old man with severe aortic regurgitation caused by a unicuspid valve mimicking quadricuspid valve. [ABSTRACT FROM AUTHOR]

A 54-year-old man with congenital bicuspid aortic valve underwent simultaneous valve repair for aortic and mitral regurgitation. Surgical technique consisted of plication of redundant aortic valve repair and mitral annuloplasty with chordal replacement. One-year follow-up transthoracic echocardiography showed no valve regurgitation. Valve repair for both bicuspid aortic valve and mitral valve regurgitation should be the first option in this subset of patients. [ABSTRACT FROM AUTHOR]

We report herein the rare case of a 53-year-old woman who developed cardiogenic shock due to an acute left atrial thrombus following replacement of the mitral valve. A definitive diagnosis was not able to be made using precordial echocardiography because of the broad, flat shape of the thrombus; however, transesophageal echocardiography imaged the thrombus in detail. The patient was initially stabilized by percutaneous cardiopulmonary support after which a thrombectomy was successfully performed. [ABSTRACT FROM AUTHOR]