A water-soluble luminescent tris(2,4,6-trichlorophenyl)methyl radical-carbazole dyad.

Organic luminescent radicals are a new class of materials with potential applications not only in light-emitting devices but also in the biochemistry field. New tris(2,4,6-trichlorophenyl)methyl (TTM) radicals with alkoxy-substituted carbazole donors were synthesized and characterized. PEG-substituted carbazole-TTM was found to be water-soluble. The water-soluble TTM radical aqueous solution showed fluorescence at 777 nm and the ability to shorten the longitudinal relaxation time (T1) of water. The concept of water-soluble luminescent radicals is expected to be used to develop a potential fluorescence and MR dual-use imaging moiety.

Perception and control: individual difference in the sense of agency is associated with learnability in sensorimotor adaptation.

Adaptive motor learning refers to the ability to adjust to novel disturbances in the environment as a way of minimizing sensorimotor errors. It is known that such processes show large individual differences and are linked to multiple perceptual and cognitive processes. On the other hand, the sense of agency refers to the subjective feeling of control during voluntary motor control. Is the sense of agency just a by-product of the control outcome, or is it actually important for motor control and learning? To answer this question, this study takes an approach based on individual differences to investigate the relationship between the sense of agency and learnability in sensorimotor adaptation. Specifically, we use an adaptive motor learning task to measure individual differences in the efficiency of motor learning. Regarding the sense of agency, we measure the perceptual sensitivity of detecting an increase or a decrease in control when the actual level of control gradually increases or decreases, respectively. The results of structure equation modelling reveal a significant influence of perceptual sensitivity to increased control on motor learning efficiency. On the other hand, the link between perceptual sensitivity to decreased control and motor learning is nonsignificant. The results show that the sense of agency in detecting increased control is associated with the actual ability of sensorimotor adaptation: people who are more sensitive in detecting their control in the environment can also more quickly adjust their behaviors to novel disturbances to acquire better control, compared to people who have a less sensitive sense of agency. Finally, the results also reveal that the processes of increasing control and decreasing control may be partially independent.

Adult ALCAPA: from histological picture to clinical features.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly that results in high mortality if left untreated. Our aim was to extend our knowledge of the histological, angiographic, and clinical characteristics of ALCAPA in order to deepen our understanding of this rare entity. CASE PRESENTATION: We were involved in the assessment, treatment, and pathological evaluation of two adult ALCAPA patients who were rescued from ventricular fibrillation and then surgically treated to establish a dual coronary artery system. Histological studies indicated various chronic ischemic changes in the myocardium, patchy fibrosis, and severely thickened arteriolar walls in both ventricles. The first patient is alive and well 11.5 years after surgical correction without any implantable cardioverter defibrillator (ICD) activations. The second patient required re-do surgery 9 months after the initial operation but subsequently died. Histologically, chronic ischemic alteration of the myocardium and thickened arteriolar walls persisted even after surgical correction, and coronary angiography (CAG) showed an extremely slow flow phenomenon even after surgical correction in both patients. The average postoperative opacification rate in the first case was 7.36 + 1.12 (n = 2) in the RCA, 3.81 + 0.51 (n = 3) in the left anterior descending (LAD) artery, and 4.08 + 0.27 (n = 4) in the left circumflex (LCx) artery. The slow flow phenomenon may represent persistent high arteriolar resistance in both ventricles. CONCLUSIONS: Seldom reported or new findings in adult ALCAPA were identified in two cases. More frequent diagnosis of adult ALCAPA can be expected because of the widespread availability of resuscitation and more advanced diagnostic modalities. Accumulation of pathological and clinical findings and confirmation of the long-term follow-up results after treatment may contribute to expanding our knowledge of this rare entity and establishing optimal treatment.

Development of a Highly Sensitive Technique for Capturing Renal Cell Cancer Circulating Tumor Cells.

PURPOSE: Liquid biopsy is becoming increasingly important as a guide for selecting new drugs and determining their efficacy. In urological cancer, serum markers for renal cell and urothelial cancers has made the development of liquid biopsy for these cancers strongly desirable. Liquid biopsy is less invasive than conventional tissue biopsy is, enabling frequent biopsies and, therefore, is considered effective for monitoring the treatment course. Circulating tumor cells (CTCs) are a representative liquid biopsy specimen. In the present study, we focused on developing our novel technology for capturing renal cell cancer (RCC)-CTCs using an anti-G250 antibody combined with new devices. Basic experiments of our technology showed that it was possible to detect RCC-CTC with a fairly high accuracy of about 95%. Also, RCC-CTC was identified in the peripheral blood of actual RCC patients. Additionally, during the treatment course of the RCC patient, change in the number of RCC-CTC was confirmed in one case. We believe that the technology we developed will be useful for determining the treatment efficacy and drug selection for the treatment of renal cell cancer (RCC). In order to solve issues such as thresholds setting of this technology, large-scale clinical trials are expected.

Branched xenopericardial roll graft replacement of an infected aortic arch graft.

Which graft material is the optimal graft material for the treatment of aortic graft infections is still a matter of controversy. We used a branched xenopericardial roll graft to replace an infected aortic arch graft as a "rescue" operation. The patient is alive and well 37 months postoperatively without recurrence of the infection and any surgical complication. This procedure may have the possibility to serve as an option for the treatment of aortic arch graft infection.

Epicardial infrared ablation to create a linear conduction block on a beating right atrium.

BACKGROUND: It is still difficult to create a secure linear conduction block on a beating heart from the epicardial side. To overcome this drawback we developed an infrared coagulator equipped with a cuboid light-guiding quartz rod. This study was designed to electrophysiologically confirm the efficacy of a new ablation probe using infrared energy in a clinical case. METHODS: The infrared light from a lamp is focused into the newly developed cuboid quartz rod, which has a rectangular distal exit-plane that allows 30 mm × 10 mm linear photocoagulation. Two pairs of electrodes were attached to the right atrium of a patient who was undergoing surgery. Each pair of electrodes was placed 10 mm from an ablation line. The change in conduction time between the two pairs of electrodes was measured during ablation. The predicted conduction time delay ratio was 1.54. RESULTS: The actual conduction time after ablation was 1.38-1.43 times longer than the pre-ablation conduction time. CONCLUSIONS: The infrared ablation using a newly developed cuboid probe made it possible to create a linear conduction block on the beating right atrial free wall clinically.

Off-pump hemostasis for left ventricular rupture after myocardial infarction with Hydrofit® and Surgicel®.

Left ventricular free wall rupture (LVFWR) is a catastrophic complication of myocardial infarction. In these cases, cardiopulmonary bypass (CPB) should be performed for left ventricular repair, but can impact hemodynamic stability. An 87-year-old man presented with acute shock. He was diagnosed with LVFWR after myocardial infarction. We describe a simple, effective, and reproducible technique to achieve hemostasis at the LVFWR site during emergency operation using Hydrofit® and Surgicel® surgical hemostatic agents. We simply placed and manually pressed the Hydrofit® and Surgicel® composite on the bleeding site. This technique provides complete hemostasis without CPB establishment.

Root aneurysm following aortic valve replacement 20 years after an arterial switch operation.

Late development of annuloaortic ectasia (AAE) and progression of aortic regurgitation (AR) are widely recognized outcomes following an arterial switch operation (ASO). We treated a 29-year-old male with AAE and rapid aortic root expansion, who underwent ASO as a neonate and aortic valve replacement (AVR) as an adult. He was diagnosed as having dextro-(D-loop) transposition of the great arteries after birth and underwent ASO at the age of 13 months. At the age of 19 years, AVR was performed for progressive AR. AAE developed after AVR. In patients who have undergone neonatal ASO, AAE may occur following AVR decades later.

Enhanced hemostasis with a sealant consisting of Hydrofit and Surgicel.

Bleeding is a serious concern during surgery for acute aortic dissections. We have used Hydrofit and Surgicel together to achieve hemostasis at the graft anastomotic sites during replacement of the ascending aorta and aortic arch. Complete hemostasis was achieved without further need for any additional sutures.

Patency of Saphenous Vein Grafts Using the PAS-Port System During Coronary Artery Bypass Surgery.

BACKGROUND: Several proximal anastomosis devices have been developed to shorten the time required for a proximal anastomosis and to avoid aortic cross-/side-clamping during coronary artery bypass grafting. This study retrospectively examined the patency of saphenous vein grafts (SVGs) using the PAS-Port System (Cardia Inc, Redwood City, CA). METHODS: From 2004 to 2014, 451 patients underwent coronary artery bypass graft operations requiring at least 1 proximal anastomosis using a PAS-Port device. A total of 802 PAS-Port devices were used, and 95.0% (762 of 802) were implanted successfully. Among the successfully implanted anastomoses, 76.8% (585 of 762) were evaluated using coronary angiography or multidimensional computed tomography, or both. The evaluations were performed between postoperative days 4 and 3,182 (mean, 319 ± 624 days). The early (1 to 365 days) and the midterm to long-term (more than 366 days) occlusion rates were examined. A complete postoperative clinical course was recorded for 70.7% of the patients. RESULTS: Overall, 93.8% (549 of 585) of the device-dependent SVGs were patent. The patency rates of device-dependent SVGs that were 1, 2, 3, 4, 5, 6, 7, and 8 years old were 90.1% ± 1.8%, 87.1% ± 2.3%, 86.1% ± 2.5%, 82.9% ± 3.3%, 80.6% ± 3.9%, 77.2% ± 5.0%, 77.2% ± 5.0%, and 70.2% ± 8.1%, respectively. The longest follow-up period was 3,182 days (8.7 years). The occlusion rate for device-dependent SVGs tended to decrease as the number of patients accumulated. CONCLUSIONS: The PAS-Port system provided acceptable SVG patency and clinical outcome for the early and midterm to long-term. There may be a learning curve for the use of PAS-Port device that affects the device-dependent SVG patency.

Pathologic Features of Lone Aortic Mobile Thrombus in the Ascending Aorta.

This report describes the case of a 79-year-old man with aortic mobile thrombus in the ascending aorta, followed by a discussion of the pathologic basis of aortic mobile thrombus formation. The patient underwent replacement of the ascending aorta. Macroscopic examination revealed an aortic wall ulcer with cholesterol-rich atherosclerotic plaque under the aortic mobile thrombus. Microscopic examination showed plaque rupture. These findings are very similar to those of plaque rupture in the coronary artery. We speculate that plaque rupture of localized aortic atherosclerosis is one of the causes of aortic mobile thrombus.

Observations of retinal vessels during intermittent pressure-augmented retrograde cerebral perfusion in clinical cases.

OBJECTIVES: Retrograde cerebral perfusion (RCP) has been used as a cerebroprotective method under hypothermic circulatory arrest (HCA) during aortic surgery. As reported in an animal model in 2005, intermittent pressure-augmented-RCP (IPA-RCP) provides more effective cerebral perfusion than RCP. In 2013, the clinical efficacy of IPA-RCP was described in terms of clinical outcomes and regional cerebral oxygen saturation using infrared spectroscopy. However, the state of cerebral microcirculation during IPA-RCP has not been investigated in humans. The aim of the present study was to investigate cerebral microcirculation during IPA-RCP in humans by assessing the retinal vessels. METHODS: Between 2013 and 2014, 8 consecutive patients underwent elective total replacement of the aortic arch for true thoracic aortic aneurysms. The IPA-RCP protocol consisted of a continuous venous pressure that was intermittently augmented at 45 mmHg for 30 s and then decreased to 20 mmHg for 120 s after isolated HCA for 300 s. The retinal vessels were assessed via non-invasive direct visualization of the cerebral microcirculation using a fundus camera. Assessments were done before cardiopulmonary bypass, during isolated HCA, and during IPA-RCP at 20 and 45 mmHg. Ratio of the diameter of retinal vessels to that of the optic disc was calculated from the diameters of the retinal arteries, veins and optic disc at each time point and was statistically examined. RESULTS: There were no neurological deficits and mortality. When compared with the control group and both IPA-RCP groups, the retinal vessels in the isolated HCA group were collapsed and the peripheral retinal vessels could not be clearly observed. The RVR was significantly larger in the control group and in both IPA-RCP groups when compared with the isolated HCA group. The RVR of the control group was similar to that of both IPA-RCP groups with regard to the retinal arteries and veins. The RVR of IPA-RCP at 45 mmHg was significantly larger than that at 20 mmHg with regard to the retinal veins. CONCLUSIONS: Our study suggested that intermittently augmented venous pressure at 45 mmHg opened the cerebrovenous vessels and enabled adequate cerebral perfusion. IPA-RCP may provide more effective cerebral perfusion under HCA in humans.

Xenopericardial roll graft replacement for infectious pseudoaneurysms and graft infections of the aorta.

BACKGROUND: Which graft material is the optimal graft material for the treatment of infected aortic aneurysms and aortic graft infections is still a matter of controversy. Orthotopic aortic reconstruction with intraoperatively prepared xenopericardial roll grafts without omentopexy was performed as the "initial" operation to treat aortic infection or as a "rescue" operation to treat graft infection. Mid-term outcomes were evaluated. METHODS: Between 2009 and 2013, orthotopic xenopericardial roll graft replacement was performed to treat eight patients (male/female: 6/2; mean age: 69.5 [55-80] yr). Graft material: equine/bovine pericardium: 2/6; type of operation: initial 4/rescue 4; omentopexy 0. Additional operation: esophagectomy 2. Mean follow-up period: 2.6 ± 1.6 (1.1-5.1) years. RESULTS: Replacement: ascending 3, arch 1 (reconstruction of neck vessels with small xenopericardial roll grafts), descending 3, and thoracoabdominal 1. Pathogens: MRSA 2, MSSA 1, Candida 1, E. coli 1, oral bacillus 1, and culture negative 2. Postoperative local recurrence of infection: 0. Graft-related complications: stenosis 0, calcification 0, non-infectious pseudoaneurysm of anastomosis 2 (surgical repair: 1/TEVAR 1). In-hospital mortality: 2 (MOF: initial 1/rescue 1); Survival rate exclusive of in-hospital deaths (~3 y): 100 %, but one patient died of lung cancer (3.6 yr). CONCLUSIONS: Because xenopericardial roll grafts are not composed of synthetic material, the replacement procedure is simpler and less invasive than the standard procedure. Based on the favorable results obtained, this procedure may have the possibility to serve as an option for the treatment of aortic infections and aortic graft infections not only as a "rescue" treatment but as an "initial" treatment as well.

Autologous Skeletal Myoblast Sheet Therapy for Porcine Myocardial Infarction Without Increasing Risk of Arrhythmia.

Safety concerns of ventricular tachyarrhythmia have arisen from some clinical trials of autologous skeletal myoblast (SkM) injection therapy. This study examined the effect and safety of SkM sheet therapy in a pig model of chronic myocardial infarction. Minipigs underwent LAD occlusion using a balloon catheter for 2 h, followed by reperfusion. After 28 days, 12 SkM sheets were transplanted onto the infarcted myocardium (sheet group n = 8); the same number of cells was also injected into the myocardium (injection group n = 7), and sham operations were performed as a control (sham group n = 7). Implantable ECG loop recorders (ILR) were placed subcutaneously on the left thorax. At 28 days after transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS), after which organs were harvested for histopathology. To assess the inflammatory and injury response, inflammation factors and high-sensitive CRP and troponin I were measured at 1, 3, 7, and 28 days after transplantation by the cytokine array method and ELISA, respectively. The sheet group showed an improvement in cardiac function compared with both the injection and sham groups (LVEF change: 5.8 ± 2.7%, -1.0 ± 2.6%, and -3.8 ± 1.8% in the sheet, injection, and sham groups, respectively, p < 0.05). VF was not detected in any group using ILR, while VT was detected in one pig from the injection group. VF was induced in 25.0%, 71.4%, and 28.6% of animals in the sheet, injection, and sham groups, respectively. In the injection group, anti-macrophage-positive cells were observed around the injected cells within the myocardium. Transmission electron microscopic images showed differentiated myofilaments, collagen layers, and a characteristic extracellular matrix surrounding the SkMs in the sheet group. Toroponin I and IL-6 levels were higher in the injection group compared with both the sheet and sham groups. SkM sheets transplanted onto infarcted myocardium improved cardiac function over SkM injection without increasing arrhythmogenicity.

Magnetic resonance imaging evaluation of remodeling by cardiac elastomeric tissue scaffold biomaterials in a rat model of myocardial infarction.

Grafting of elastomeric biomaterial scaffolds may offer a radical strategy for the prevention of heart failure after myocardial infarction by increasing efficacy of stem cell delivery as well as acting as mechanical restraint devices to constrain scar expansion. Biomaterials can be partially optimized in vitro, but their in vivo performance is most critical and should ideally be monitored serially and noninvasively. We used magnetic resonance imaging (MRI) to assess three scaffold materials with a range of structural moduli equal to or greater than myocardial tissue: poly(glycerol sebacate) (PGS), poly(ethyleneterephathalate)/dimer fatty acid (PED), and TiO(2)-reinforced PED (PED-TiO(2)). Patches, 1 cm in diameter, were grafted onto the hearts of infarcted rats, with biomaterial-free infarcted rat hearts used as controls. MRI was able to determine scaffold size and location on the heart and identified unexpectedly rapid in vivo degradation of the PGS compared with previous in vitro testing. PED patches did not withstand in vivo attachment, but the more rigid PED-TiO(2) material was detrimental to heart function, increasing chamber and scar sizes and reducing ejection fractions compared with controls. In contrast, the mechanically compatible PGS scaffold successfully reduced hypertrophy, giving it potential for limiting excessive postinfarct remodeling. PGS was unable to support systolic function, but it would be suitable for strategies to deliver cardiac stem/progenitor cells, to limit remodeling during the period of functional cellular integration, and to degrade after cell assimilation by the heart. This work has also shown for the first time the value of using MRI as a noninvasive tool for evaluating and optimizing therapeutic biomaterials in vivo.

Simultaneous use of argatroban and heparin during cardiopulmonary bypass.

Heparin is the routine anticoagulant for cardiopulmonary bypass, but complications due to heparin are often reported. This study assessed argatroban as an alternative to heparin. Normothermic cardiopulmonary bypass with hemodilution was performed for 2 h in 15 dogs (mean weight, 9.8 kg) randomly assigned to 3 groups of 5 each. The controls were given heparin 200 IU x kg(-1) before cardiopulmonary bypass; group A had argatroban infused continuously at a rate of 20 microg x kg(-1) x min(-1); group H/A had half doses of both heparin (100 IU x kg(-1)) and argatroban (10 microg x kg(-1) x min(-1)). Blood samples were collected at 5 time points during the experiment. Activated clotting time, hemoglobin level, platelet counts, and serum concentrations of fibrinogen, antithrombin III, and thrombin-antithrombin III complex were measured. The platelet count was reduced significantly, and the production of thrombin-antithrombin III complex was inhibited in group H/A. Activated clotting time remained <300 sec at all time points in group A, but it was maintained at approximately 400 sec in group H/A. Fibrinogen and antithrombin III levels were reduced to half in all groups after initiation of cardiopulmonary bypass. The simultaneous use of heparin and argatroban infusion might be useful for cardiopulmonary bypass with hemodilution.