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We have investigated the depletion of the surface Li abundance in low-mass main-sequence stars of 0.8–1.2 M[sub ⊙]. We compare our evolutionary models with the observed Li abundances of G and K dwarfs in young open clusters (mainly the Pleiades and the Hyades clusters) and the Sun. Standard models with no mixing in the radiative zone give a N[sub Li]–T[sub eff] relation that roughly coincides with the relation for the lower envelope of the Pleiades. Standard models, however, give hardly any depletion of Li during the period between the Pleiades and Hyades ages. We have considered non-standard mixing in the radiative zone as a result of overshooting from the lower boundary of the convective envelope and rotationally induced slow turbulence. The overshooting depletes more Li in less-massive stars, while the rotational mixing affects Li depletion in a similar fashion over the entire mass range considered. We have found that reasonable agreement with observations is obtained if these types of mixing are included in the main-sequence evolution but suppressed in the pre-main-sequence phase. [ABSTRACT FROM AUTHOR]

Objectives: Our goal was to analyse the relationships between aortic surface irregularity and a type 1 endoleak (T1EL) after a thoracic endovascular repair using the Najuta fenestrated stent graft., Methods: The patients who were treated using the Najuta stent graft for an intact aortic arch aneurysm at the Saitama Cardiovascular and Respiratory Center between June 2013 and June 2017 were analysed retrospectively. The primary end point was the occurrence of a T1EL. The gap between a virtual aorta and the patient's aortic wall at the stent graft fixation was calculated over the whole circumference at 1 mm intervals, and gap distribution mapping was performed. The rate of freedom from a T1EL was estimated using the Kaplan-Meier method and compared between the patients with or without a continuously malapposed region of >1 mm from the branches to the aneurysm., Results: Twenty-one patients were analysed. During the mean follow-up period of 21.7 months, 4 patients were confirmed to have T1ELs. Three of the T1Els were detected during the perioperative period and occurred through a fenestration. The remaining patient had a T1EL 2 years postoperatively. The gap distribution mapping confirmed the presence of a continuously malapposed region of >1 mm from the cervical branch to the aneurysm postoperatively in 4 patients with T1ELs. Patients who had a continuously malapposed region of >1 mm showed a statistically lower T1EL rate than those without (p < 0.001). Malapposed regions defined using the gap distribution mapping were consistent with flow channels through T1EL fenestrations detected using the perioperative computed tomography data., Conclusions: The gap distribution mapping could be useful to predict the occurrence of T1ELs in patients with the Najuta stent graft., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

There is an essential demand for developing biocompatible grafts for knee anterior cruciate ligament reconstruction (ACLR). This study investigated cell infiltration into decellularized bovine tendon xenografts using a rat knee ACLR model. Twelve-week-old Sprague-Dawley rats were used. At weeks 1, 2, 4, 8, 16, 26, and 52 (each period, n = 6) after ACLR, rats receiving decellularized bovine tendon (group D, n = 42) or autologous tendon (group A, n = 42) as grafts underwent peritibial bone tunnel bone mineral density (BMD), histological, and immunohistological assessments. BMD increased over time in both the groups until week 16 and then remained unchanged without exhibiting significant differences between the groups. Initially, cellularity in group D was lower than that in group A; however, by weeks 4-8, both the groups were comparable to the native anterior cruciate ligament group and cellularity remained unchanged until week 52. Initially, group A had more M1 macrophages, indicating inflammation, whereas group D had more M2 macrophages, indicating tissue regeneration. Nonetheless, the M1 and M2 macrophage counts of both the groups were comparable at most times. This study revealed the excellent recellularization and tendon-bone integration abilities of decellularized tendons using a cross-species model., (© 2022. The Author(s).)

Calcified artery lesions cause stent under-expansion and increase the risk of in-stent restenosis and stent thrombosis. Cutting balloons facilitate the fracturing of calcification prior to stent implantation, although vessel dissection and perforation are potential issues. In clinical practice, calcifications having maximum calcium angles ≤ 180° are rarely fractured during conventional balloon angioplasty. We hypothesize that the lesion/device diameter ratio and the number of blades facing a non-circular calcified lesion may be crucial for fracturing the calcification while avoiding vessel injury. The geometries of the cutting balloons were constructed and their finite-element models were generated by folding and wrapping the balloon model. Numerical simulations were performed for balloons with five different diameters and two types of blade directions in a 180° calcification model. The calcification expansion ability was distinctly higher when two blades faced the calcification than when one blade did. Moreover, when two blades faced the calcification model, larger maximum principal stresses were generated in the calcification even when using undersized balloons with diameters reduced by 0.25 or 0.5 mm from the reference diameter, when compared with the case where one blade faced the calcified model and a balloon of diameter equal to the reference diameter was used. When two blades faced the calcification, smaller stresses were generated in the artery adjacent to the calcification; further, the maximum stress generated in the artery model adjacent to the calcification under the rated pressure of 12 atm when employing undersized balloons was smaller than that when only one blade faced the calcification and when lesion-identical balloon diameters were used under a nominal pressure of 6 atm. Our study suggested that undersized balloons of diameters 0.25 or 0.5 mm less than the reference diameter might be effective in not only expanding the calcified lesion but also reducing the risk of dissection., Competing Interests: The authors have declared that no competing interests exist.

Background: The appropriate balloon-to-artery ratio (BAR) for cutting balloons (CBs), to expand calcified lesions without increasing the risk of coronary artery perforation is unknown. This study investigated the effects of BAR on stress levels in the calcification and at the borders of the coronary artery adjacent to the calcification to determine an appropriate BAR. Methods and Results: A custom-designed folding process of the CB model was developed. The CB models were deployed in a coronary artery model with a reference diameter of 3.0 mm, length of 24 mm, and wall thickness of 0.8 mm equipped with a 50% diameter stenotic, 360° concentric, 400-µm, and 5-mm-long calcification. Finite element analysis of the expansion of CBs with diameters increasing from 2.0 to 3.0 mm in 0.25-mm increments, corresponding to BARs from 0.67 : 1 to 1 : 1, was conducted with pressures up to 12 atm. Decreasing the CB by 0.25 and 0.5 mm (relative to the reference diameter of 3 mm) preserved maximum principal tensile stress levels comparable to that of a CB with a BAR of 1 : 1 while distinctly reducing the stress at the border of the artery adjacent and calcification. Conclusions: Selecting a CB that is 0.25 or 0.5 mm lower than the 3-mm reference diameter may be the first choice to effectively fracture calcifications without increasing the risk of severe artery dissection and perforation., Competing Interests: K.I. is a member of Circulation Reports’ Editorial Team. The other authors declare that they have no conflicts of interest., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Background: Underfilled transcatheter aortic-valve implantation with ad hoc post-dilation is a therapeutic option for patients with borderline annuli to avoid acute complication. The effects of this technique on valve leaflet behavior, hydrodynamic performances, and paravalvular leakage (PVL) using patient-specific three-dimensional (3D) aortic-valve models were investigated. Methods and Results: A female octogenarian patient was treated with this technique by using a 23-mm Sapien-XT. Patient-specific models were constructed from pre-procedure computed tomography (CT) data. Change in aortic annulus areas during systolic/diastolic phases and post-procedure stent areas were adjusted to those of the patient. The following was performed: (1) -3 cc initial and -2 cc underfilled post-dilation to the scale-down model by adjusting percent oversizing; and (2) -1 cc initial underfilling, nominal volume, and repeat nominal volume post-dilation using the patient-specific model. Underfilling was associated with higher %PVL. Observation using a high-speed camera revealed distorted leaflets after underfilled implantation, with a longer valve-closing time and smaller effective orifice areas, especially in the -3 cc underfilled implantation. Micro-CT analysis revealed that the transcatheter valves shifted to the opposite side of the large annulus calcification after post-dilation and reduced the malapposition there., Conclusions: Excessive underfilled implantation showed unacceptable acute hemodynamics. Abnormal leaflet motions after underfilled implantation raised concerns about durability. Flow simulations using patient-oriented 3D models could help to investigate hemodynamics, leaflet motions, and the PVL mechanism.

Assembling three-dimensional (3D) tissues from single cells necessitates the use of various advanced technological methods because higher-density tissues require numerous complex capillary structures to supply sufficient oxygen and nutrients. Accordingly, creating healthy culture conditions to support 3D cardiac tissues requires an appropriate balance between the supplied nutrients and cell metabolism. The objective of this study was to develop a simple and efficient method for low-temperature cultivation (< 37 °C) that decreases cell metabolism for facilitating the buildup of 3D cardiac tissues. We created 3D cardiac tissues using cell sheet technology and analyzed the viability of the cardiac cells in low-temperature environments. To determine a method that would allow thicker 3D tissues to survive, we investigated the cardiac tissue viability under low-temperature culture processes at 20-33.5 °C and compared it with the viability under the standard culture process at 37 °C. Our results indicated that the standard culture process at 37 °C was unable to support higher-density myocardial tissue; however, low-temperature culture conditions maintained dense myocardial tissue and prevascularization. To investigate the efficiency of transplantation, layered cell sheets produced by the low-temperature culture process were also transplanted under the skin of nude rats. Cardiac tissue cultured at 30 °C developed denser prevascular networks than the tissue cultured at the standard temperature. Our novel findings indicate that the low-temperature process is effective for fabricating 3D tissues from high-functioning cells such as heart cells. This method should make major contributions to future clinical applications and to the field of organ engineering.

Background: Blood-contacting devices have contributed to improving the treatment of patients. However, thrombus formation at the interface between a connector and tube is still a potential source of thrombus-related complications that induce stroke or myocardial infarction. We aimed to develop a non-blood-contacting real-time method for visualizing thrombus formation, and to experimentally investigate the time-dependent phenomenon of thrombus formation at the interface between a connector and a tube in a medical device., Methods and Findings: An optical coherence tomography device with a center wavelength of 1330 nm was used to visualize thrombus formation during porcine blood circulation for 50 min in a closed 50-mL circulation system isolated from ambient air. The thrombus formation sites at the interface between a tube and connector were visualized. The area of the thrombus formation at the interface between the inlet of the connector and the tube was found to be 0.012 ± 0.011 mm2. Conversely, at the interface between the outlet of the connector and the tube, the area was found to be 0.637 ± 0.306 mm2. Thus, significantly larger amounts of thrombus were formed at the outlet interface (p < 0.01). The thrombus formation area at the outlet interface increased over time. Conversely, the area of thrombus formation showed repeated increasing and decreasing behavior at the inlet interface. Flow visualization with particle image velocimetry showed the presence of a flow separated area in the minimal flow phase at the inlet interface and a large recirculating slow flow region at the outlet interface in the minimal flow phase. These data suggested that the recirculating stagnant flow region contributed to thrombus growth., Conclusions: The method presented here was effective in quantitatively assessing time-dependent phenomena of thrombus formation at the connector-tube interface. The method may contribute to the assessment of thrombogenicity of a novel design of connector.

Background: The mechanical interaction between blood vessels and medical devices can induce strains in these vessels. Measuring and understanding these strains is necessary to identify the causes of vascular complications. This study develops a method to measure the three-dimensional (3D) distribution of strain using tomographic particle image velocimetry (Tomo-PIV) and compares the measurement accuracy with the gauge strain in tensile tests., Methods and Findings: The test system for measuring 3D strain distribution consists of two cameras, a laser, a universal testing machine, an acrylic chamber with a glycerol water solution for adjusting the refractive index with the silicone, and dumbbell-shaped specimens mixed with fluorescent tracer particles. 3D images of the particles were reconstructed from 2D images using a multiplicative algebraic reconstruction technique (MART) and motion tracking enhancement. Distributions of the 3D displacements were calculated using a digital volume correlation. To evaluate the accuracy of the measurement method in terms of particle density and interrogation voxel size, the gauge strain and one of the two cameras for Tomo-PIV were used as a video-extensometer in the tensile test. The results show that the optimal particle density and interrogation voxel size are 0.014 particles per pixel and 40 × 40 × 40 voxels with a 75% overlap. The maximum measurement error was maintained at less than 2.5% in the 4-mm-wide region of the specimen., Conclusions: We successfully developed a method to experimentally measure 3D strain distribution in an elastic silicone material using Tomo-PIV and fluorescent particles. To the best of our knowledge, this is the first report that applies Tomo-PIV to investigate 3D strain measurements in elastic materials with large deformation and validates the measurement accuracy.

Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure., Competing Interests: The authors declare no conflict of interest.

Background: Clinical studies for assessing the effectiveness and safety in a premarketing setting are conducted under time and cost constraints. In recent years, postmarketing data analysis has been given more attention. However, to our knowledge, no studies have compared the effectiveness and the safety between the pre- and postmarketing settings. In this study, we aimed to investigate the importance of the postmarketing data analysis using clinical data., Methods and Findings: Studies on capsule endoscopy with rich clinical data in both pre- and postmarketing settings were selected for the analysis. For effectiveness, clinical studies published before October 10, 2015 comparing capsule endoscopy and conventional flexible endoscopy measuring the detection ratio of obscure gastrointestinal bleeding were selected (premarketing: 4 studies and postmarketing: 8 studies) from PubMed (MEDLINE), Cochrane Library, EMBASE and Web of Science. Among the 12 studies, 5 were blinded and 7 were non-blinded. A time series meta-analysis was conducted. Effectiveness (odds ratio) decreased in the postmarketing setting (premarketing: 5.19 [95% confidence interval: 3.07-8.76] vs. postmarketing: 1.48 [0.81-2.69]). The change in odds ratio was caused by the increase in the detection ratio with flexible endoscopy as the control group. The efficacy of capsule endoscopy did not change between pre- and postmarketing settings. Heterogeneity (I2) increased in the postmarketing setting because of one study. For safety, in terms of endoscope retention in the body, data from the approval summary and adverse event reports were analyzed. The incidence of retention decreased in the postmarketing setting (premarketing: 0.75% vs postmarketing: 0.095%). The introduction of the new patency capsule for checking the patency of the digestive tract might contribute to the decrease., Conclusions: Effectiveness and safety could change in the postmarketing setting. Therefore, time series meta-analyses could be useful to continuously monitor the effectiveness of medical device in clinical practices.

Multilayered cell sheets have been produced from bone marrow-derived mesenchymal stem cells (MSCs) for investigating their adhesion properties onto native porcine heart tissue. Once MSCs reached confluence after a 7-day culture on a temperature-responsive culture dish, a MSCs monolayer spontaneously detached itself from the dish, when the culture temperature was reduced from 37 to 20°C. The basal extracellular matrix (ECM) proteins of the single cell sheet are preserved, because this technique requires no proteolytic enzymes for harvesting cell sheet, which become a basic building block for assembling a multilayer cell sheet. The thickness of multilayered cell sheets made from three MSC sheets was found to be approximately 60 μm. For investigating the adhesion properties of the basal and apical sides, the multilayered cell sheets were transplanted onto the surface of the heart's left ventricle. Multilayered cell sheets were histological investigated at 15, 30, 45 and 60 minutes after transplantation by hematoxylin eosin (HE) and azan dyes to determine required time for the adhesion of the multilayered sheets following cell-sheet transplantation. The results showed that only the basal side of multilayered cell sheets significantly enhanced the sheets adhesion onto the surface of heart 30 minutes after transplantation. This study concluded that (1) cell sheets had to be transplanted with its basal side onto the surface of heart tissue and (2) at least 30 minutes were necessary for obtaining the histological adhesion of the sheets to the heart tissue. This study provided clinical evidence and parameters for the successful application of MSC sheets to the myocardium and allowed cell sheet technology to be adapted clinical cell-therapy for myocardial diseases.

In this paper, we present a general, fibril-based structural constitutive theory which accounts for three material aspects of crosslinked filamentous materials: the single fibrillar force response, the fibrillar network model, and the effects of alterations to the fibrillar network. In the case of the single fibrillar response, we develop a formula that covers the entropic and enthalpic deformation regions, and introduce the relaxation phase to explain the observed force decay after crosslink breakage. For the filamentous network model, we characterize the constituent element of the fibrillar network in terms its end-to-end distance vector and its contour length, then decompose the vector orientation into an isotropic random term and a specific alignment, paving the way for an expanded formalism from principal deformation to general 3D deformation; and, more important, we define a critical core quantity over which macroscale mechanical characteristics can be integrated: the ratio of the initial end-to-end distance to the contour length (and its probability function). For network alterations, we quantitatively treat changes in constituent elements and relate these changes to the alteration of network characteristics. Singular in its physical rigor and clarity, this constitutive theory can reproduce and predict a wide range of nonlinear mechanical behavior in materials composed of a crosslinked filamentous network, including: stress relaxation (with dual relaxation coefficients as typically observed in soft tissues); hysteresis with decreasing maximum stress under serial cyclic loading; strain-stiffening under uniaxial tension; the rupture point of the structure as a whole; various effects of biaxial tensile loading; strain-stiffening under simple shearing; the so-called "negative normal stress" phenomenon; and enthalpic elastic behaviors of the constituent element. Applied to compacted collagen gels, the theory demonstrates that collagen fibrils behave as enthalpic elasticas with linear elasticity within the gels, and that the macroscale nonlinearity of the gels originates from the curved fibrillar network. Meanwhile, the underlying factors that determine the mechanical properties of the gels are clarified. Finally, the implications of this study on the enhancement of the mechanical properties of compacted collagen gels and on the cellular mechanics with this model tissue are discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: We conducted in vivo examinations of a newly designed stentless mitral valve (SMV), formed by suturing 2 leaflets with the "legs" serving as chorda tendinea, made from bovine pericardium, to a flexible ring. METHODS AND RESULTS: Seven pigs underwent implantation of the SMV constructed with a 23-mm (n=5) or 25-mm (n=2) Duran ring. Baseline echocardiography examinations were used to evaluate the annular anteroposterior diameter, and distance between the mitral annulus (MA) and papillary muscles (PMs) to determine SMV-leg length. After removing the native valve, the SMV-legs were fixed to the anterior and posterior PMs, followed by fixation of the ring to the native MA. Immediately after surgery, all animals presented none or trivial mitral regurgitation, with mean and peak trans-SMV pressure gradient values of 1.9±0.8 and 6.0±3.1 mmHg, respectively. The mean length of the SMV-leg was 19.4±3.9 mm, which correlated with the distance between anterior and posterior MA-PM (r=0.96 and 0.94, respectively, P<0.01 for both). The discrepancy between the anteroposterior diameter of the ring (outside diameter) and that of the native valve was 1.0±2.9 mm, which correlated with the trans-SMV pressure gradient (r=0.81, P=0.025)., Conclusions: In our preliminary study, the SMV demonstrated excellent diastolic inflow dynamics and closing function in vivo. Preoperative precise assessment of MV configuration may serve as a basis for selection of appropriate ring size and SMV-leg length.

Fibroblast-mediated compaction of collagen gels attracts extensive attention in studies of wound healing, cellular fate processes, and regenerative medicine. However, the underlying mechanism and the cellular mechanical niche still remain obscure. This study examines the mechanical behaviour of collagen fibrils during the process of compaction from an alternative perspective on the primary mechanical interaction, providing a new viewpoint on the behaviour of populated fibroblasts. We classify the collagen fibrils into three types - bent, stretched, and adherent - and deduce the respective equations governing the mechanical behaviour of each type; in particular, from a putative principle based on the stationary state of the instantaneous Hamiltonian of the mechanotransduction system, we originally quantify the stretching force exerted on each stretched fibrils. Via careful verification of a structural elementary model based on this classification, we demonstrate a clear physical picture of the compaction process, quantitatively elucidate the panorama of the micro mechanical niche and reveal an intrinsic biphasic relationship between cellular traction force and matrix elasticity. Our results also infer the underlying mechanism of tensional homoeostasis and stress shielding of fibroblasts. With this study, and sequel investigations on the putative principle proposed herein, we anticipate a refocus of the research on cellular mechanobiology, in vitro and in vivo., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Total cavopulmonary connection (TCPC), a typical kind of Fontan procedure, is commonly used in the treatment of a functional single ventricle. The palliative cardiothoracic procedure is performed by connecting the superior vena cava and the inferior vena cava to the pulmonary arteries. Due to the difficulty of direct study in vivo, in this paper, computational fluid dynamics (CFD) was introduced to estimate the outcomes of patient-specific TCPC configuration. We mainly focused on the influence of blood pulsation and respiration. Fast Fourier transforms method was employed to separate the measured flow conditions into the rate of breath and heart beat. Blood flow performance around the TCPC connection was investigated by analyzing the results of time-varying energy losses, blood flow distribution rate, local pressure, and wall shear stress distributions. It was found that the value of energy loss including the influence of respiration was 1.5 times higher than the value of energy loss disregarding respiratory influences. The results indicated that the hemodynamic outcomes of TCPC treatment are obviously influenced by respiration. The influence of respiration plays an important role in estimating the results of TCPC treatment and thus should be included as one of the important conditions of computational haemodynamic analysis.

Objectives: To determine (1) the proportion and number of clinically relevant alarms based on the type of monitoring device; (2) whether patient clinical severity, based on the sequential organ failure assessment (SOFA) score, affects the proportion of clinically relevant alarms and to suggest; (3) methods for reducing clinically irrelevant alarms in an intensive care unit (ICU)., Design: A prospective, observational clinical study., Setting: A medical ICU at the University of Tokyo Hospital in Tokyo, Japan., Participants: All patients who were admitted directly to the ICU, aged ≥18 years, and not refused active treatment were registered between January and February 2012., Methods: The alarms, alarm settings, alarm messages, waveforms and video recordings were acquired in real time and saved continuously. All alarms were annotated with respect to technical and clinical validity., Results: 18 ICU patients were monitored. During 2697 patient-monitored hours, 11 591 alarms were annotated. Only 740 (6.4%) alarms were considered to be clinically relevant. The monitoring devices that triggered alarms the most often were the direct measurement of arterial pressure (33.5%), oxygen saturation (24.2%), and electrocardiogram (22.9%). The numbers of relevant alarms were 12.4% (direct measurement of arterial pressure), 2.4% (oxygen saturation) and 5.3% (electrocardiogram). Positive correlations were established between patient clinical severities and the proportion of relevant alarms. The total number of irrelevant alarms could be reduced by 21.4% by evaluating their technical relevance., Conclusions: We demonstrated that (1) the types of devices that alarm the most frequently were direct measurements of arterial pressure, oxygen saturation and ECG, and most of those alarms were not clinically relevant; (2) the proportion of clinically relevant alarms decreased as the patients' status improved and (3) the irrelevance alarms can be considerably reduced by evaluating their technical relevance.

This study experimentally investigated the instability of flow impingement in a cerebral aneurysm, which was speculated to promote the degradation of aneurysmal wall. A patient-specific, full-scale and elastic-wall replica of cerebral artery was fabricated from transparent silicone rubber. The geometry of the aneurysm corresponded to that found at 9 days before rupture. The flow in a replica was analysed by quantitative flow visualization (stereoscopic particle image velocimetry) in a three-dimensional, high-resolution and time-resolved manner. The mid-systolic and late-diastolic flows with a Reynolds number of 450 and 230 were compared. The temporal and spatial variations of near-wall velocity at flow impingement delineated its inherent instability at a low Reynolds number. Wall shear stress (WSS) at that site exhibited a combination of temporal fluctuation and spatial divergence. The frequency range of fluctuation was found to exceed significantly that of the heart rate. The high-frequency-fluctuating WSS appeared only during mid-systole and disappeared during late diastole. These results suggested that the flow impingement induced a transition from a laminar regime. This study demonstrated that the hydrodynamic instability of shear layer could not be neglected even at a low Reynolds number. No assumption was found to justify treating the aneurysmal haemodynamics as a fully viscous laminar flow.

In vitro scaling up of bioengineered tissues is known to be limited by diffusion issues, specifically a lack of vasculature. Here, we report a new strategy for preserving cell viability in three-dimensional tissues using cell sheet technology and a perfusion bioreactor having collagen-based microchannels. When triple-layer cardiac cell sheets are incubated within this bioreactor, endothelial cells in the cell sheets migrate to vascularize in the collagen gel, and finally connect with the microchannels. Medium readily flows into the cell sheets through the microchannels and the newly developed capillaries, while the cardiac construct shows simultaneous beating. When additional triple-layer cell sheets are repeatedly layered, new multi-layer construct spontaneously integrates and the resulting construct becomes a vascularized thick tissue. These results confirmed our method to fabricate in vitro vascularized tissue surrogates that overcomes engineered-tissue thickness limitations. The surrogates promise new therapies for damaged organs as well as new in vitro tissue models.

In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications.

Objective: The study objective was to evaluate various types of Norwood arch reconstruction methods and to show the factors that affect the cardiac workload of the single ventricle. The Norwood procedure is one of the most challenging congenital heart surgeries. Several aortic arch reconstruction techniques have been reported to avoid recoarctation, ensure coronary perfusion, and improve long-term outcomes. Inside the arch, complicated turbulent flow is generated; however, little is known about the cause of the disadvantageous inefficient flow and the surgical techniques to avoid it., Methods: We created patient-specific computational hemodynamic models of 9 patients who underwent different types of arch reconstruction methods. Four patients had aortic atresia, and 5 patients had aortic stenosis. Flow profiles were defined by echocardiography data corrected with body surface area. Turbulent pulsatile flow was analyzed with the finite volume method. Flow energy loss was calculated to estimate cardiac workload, and wall shear stress was calculated to estimate vessel wall stiffness increase., Results: Recoarctation and acute arch angles increased wall shear stress and energy loss. In the patients with aortic atresia, a longitudinal incision toward the descending aorta was effective in creating a smooth arch angle. In the patients with aortic stenosis, arch repair with the Damus-Kaye-Stansel procedure in a single anastomotic site was effective in creating sufficient anastomosis space and a smooth arch angle., Conclusions: Creation of a large anastomotic space and a smooth aortic arch angle reduced wall shear stress and energy loss, and should improve long-term cardiac performance after the Norwood procedure., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: We have reconstructed aortic valves using autologous pericardium treated with glutaraldehyde since April 2007. However, the strength of the human pericardium has not been confirmed. We compared tensile strength between glutaraldehyde-treated human pericardium and aortic valve leaflets with various degrees of calcification to determine their suitability for use in aortic valve reconstruction., Methods: We measured the ultimate tensile strength and elasticity of samples of glutaraldehyde-treated pericardia (n = 8), non-calcified (n = 12), calcified (n = 9) and decalcified (n = 21) aortic leaflets collected from 23 patients who underwent aortic valve surgery. Aortic valves were decalcified using a cavitational ultrasonic surgical aspirator. The pericardium was immersed in 0.6% buffered glutaraldehyde for 10 minutes and then rinsed three times for 6 minutes each in normal saline., Results: The ultimate tensile strength of the glutaraldehyde-treated human pericardium, non-calcified, calcified and decalcified leaflets was 10, 2.8, 1.0 and 0.8 MPa, respectively., Conclusions: The ultimate tensile strength of glutaraldehyde-treated human pericardium was 4 times higher than non-calcified leaflets, indicating its suitability for application to aortic valve reconstruction. Calcified leaflets were slightly stronger than decalcified leaflets. Thus, calcification can be removed without altering the tensile strength of valve materials.

Background and Purpose: The decision as to the treatment of incidental IAs is complex. There are no certain quantitative methods that can be used to evaluate the risk of rupture in IAs. In recent years, CFD technology has been recognized as a potential risk-analysis tool. The aim of this article was to propose a hemodynamic parameter, EL, to determine the effects of stable unruptured aneurysms and of those that ruptured during the subsequent observation period., Materials and Methods: Four incidentally found ICA-PcomA aneurysms ruptured during the period of observation (ruptured-IAs). Another 26 unruptured aneurysms (stable-IAs) with similar location, size, and morphology were compared for the differences in hemodynamic factors, such as EL and WSS., Results: The EL calculated at the ruptured-IAs was nearly 5 times higher on average than that at the stable-IAs (ruptured, 0.00374 ± 0.0011; stable, 0.000745 ± 0.0001 mW/mm(3), P < .001). However, there was no difference between the ruptured and stable groups according to the results of time-averaged WSS (P = .8) for ruptured- and stable-IAs. According to flow visualization, though the mean average inflow speed of ruptured-IAs was 2 times higher than that of the stable-IAs, the flow inside ruptured-IAs appeared to undergo longer resident tracks, with stronger impact on the aneurysm wall. On the contrary, the flow inside stable-IAs passed smoothly through the aneurysms., Conclusions: These preliminary results indicated that EL may be a useful parameter for the quantitative estimation of the risks of rupture for IAs.

Microscopic and molecular analyses showed the presence of endobacteria inside the mycelia of four out of twelve nitrous oxide (N(2)O)-producing fungal isolates identified as Mortierella elongata. The 16S rRNA gene was successfully amplified with DNA extracted directly from the endobacterium-containing fungal strains and all sequences were related to that of Candidatus Glomeribacter gigasporarum in the family Burkholderiaceae. Bacterial endotoxin was detected in the endobacterium-positive fungal strains but only trace levels were found in endobacterium-negative strains. No significant relationship was found between the fungal N(2)O-producing activity and the presence of endobacteria.

The rdw rat is a hereditary hypothyroid strain isolated from Wistar-Imamichi rats. In the present study, adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint stress (120 min) were examined in rdw adult male rats. ACTH response to restraint stress was higher in rdw rats than in hetero control rats. The plasma concentrations of corticosterone were lower in rdw rats than in control rats during the first 30 min after the onset of stress. Both ACTH and corticosterone responses to restraint stress in rdw rats recovered to control levels after thyroxine (T4) replacement therapy. These results suggest that hereditary hypothyroidism causes adrenal dysfunction directly and that hypersecretion of ACTH is a result of reduced corticosterone in rdw rats.

Modern imaging technologies, such as computed tomography (CT) angiography, magnetic resonance (MR) angiography, and digital subtraction (DS) angiography are widely used for pretreatment evaluation of cerebral aneurysms, but the relative accuracies of these modalities are unclear. This study compared the measurements of aneurysm neck and dome height and width on CT angiography, time-of-flight (TOF)-MR angiography, and DS angiography using a three-dimensional workstation. An elastic model of a side-wall aneurysm was connected to an artificial heart pulsatile circuit system. The aneurysm model was prepared using a silicone membrane of 0.6-mm thickness under normal physiological circulation parameters. Using this aneurysm model, three-dimensional TOF-MR angiography, contrast-enhanced CT angiography, and DS angiography were performed. Source images were post-processed on a dedicated workstation to calculate the aneurysm size. DS angiography measurements were found to be the most accurate. In contrast, aneurysm neck sizes measured on CT angiography were significantly wider than actual values (p < 0.05) and aneurysm heights measured using TOF-MR angiography were significantly lower than actual values (p < 0.01). In this in-vitro model, at least one aneurysm dimension measured with CT angiography and with TOF-MR angiography differed significantly from actual values. Aneurysm neck width markedly affects therapeutic planning, as a wide neck requires craniotomy or endovascular treatment using an adjunctive device, so inaccuracies should be considered when aneurysm treatment is planned using modern methods of visualization.

We report a case of tako-tsubo cardiomyopathy associated with brain metastasis of seminoma. This disease is characterized by transient cardiac wall motion abnormalities, electrocardiographic changes and minimal myocardial enzymatic release. During the hospital days, acute congestive heart failure suddenly appeared. The electrocardiogram showed a ST segment elevation in V1-3 and a giant negative T wave in I, aVL, aVF and V3-6. The echocardiogram revealed left ventricular dysfunction with severe hypokinesis to akinesis of anterior and apical wall regions, and hyperkinesis of the basal wall despite the lack of cardiac enzymatic abnormalities. With proper treatment, the patient's overall condition, wall motion and electrocardiographic abnormalities greatly improved.