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Neurologic adverse events (NAEs) are a major complication after pulmonary endarterectomy (PEA) performed under periods of deep hypothermic circulatory arrest (HCA) for chronic thromboembolic pulmonary hypertension. We modified the PEA strategy to prevent NAEs and evaluated the effectiveness of these modifications.We reviewed the surgical outcomes of 87 patients divided into the following three groups based on the surgical strategy used: group S (n = 49), periods of deep HCA with alpha-stat strategy; group M1 (n = 19), deep HCA with modifications of slower cooling and rewarming rates and the pH-stat strategy for cooling: and group M2 (n = 13), multiple short periods of moderate HCA.PEA provided significant improvement of pulmonary hemodynamics in each group. Sixteen (29%) of the 49 group S patients suffered NAEs, associated with total circulatory arrest time (cutoff, 57 min) and Jamieson type I disease. The Group M1 and M2 patients did not suffer NAEs, although the group M1 patients had prolonged cardiopulmonary bypass (CPB) and more frequent respiratory failure.NAEs were common after PEA performed under periods of deep HCA. The modified surgical strategy could decrease the risk of NAEs but increase the risk of respiratory failure. Multiple short periods of moderate HCA may be useful for patients at risk of NAEs.

Background Homebound status is one of the most important risk factors associated with functional decline and long-term care in older adults. Studies show that neighborhood built environment and community social capital may be related to homebound status. This study aimed to clarify the association between homebound status for community-dwelling older adults and community environment-including social capital and neighborhood built environment-in rural and urban areas. Methods We surveyed people aged 65 years and older residing in three municipalities of Niigata Prefecture, Japan, who were not certified as requiring long-term care. The dependent variable was homebound status; explanatory variables were community-level social capital and neighborhood built environment. Covariates were age, sex, household, marital status, socioeconomic status, instrumental activities of daily living, the Geriatric Depression Scale-15, self-rated health, number of diseases under care, and individual social capital. The association between community social capital or neighborhood built environment and homebound status, stratified by rural/urban areas, was investigated using multilevel logistic regression analysis. Results Among older adults (n = 18,099), the homebound status prevalence rate was 6.9% in rural areas and 4.2% in urban areas. The multilevel analysis showed that, in rural areas, fewer older adults were homebound in communities with higher civic participation and with suitable parks or pavements for walking and exercising. However, no significant association was found between community social capital or neighborhood built environment and homebound status for urban older adults. Conclusions Community social capital and neighborhood built environment were significantly associated with homebound status in older adults in rural areas.

Vagal afferents regulate numerous physiological functions including arterial blood pressure, heart rate, breathing, and nociception. Cell bodies of vagal afferents reside in the inferior vagal (nodose) ganglia and their stimulation by various means is being considered as a way to regulate cardiorespiratory responses and control pain sensations. Stimulation of the nodose by exposure to infrared light is recently being considered as a precise way to elicit responses. These responses would likely involve the activity of temperature-sensitive membrane-bound channels. While papers have been published to track the expression of these transient receptor potential ion channels (TRPs), further studies are warranted to determine the in situ expression of the endogenous TRP proteins in the nodose ganglia to fully understand their pattern of expression, subcellular locations, and functions in this animal model. TRP ion channels are a superfamily of Na

Retinoic acid, an active form of vitamin A, plays very important roles in mammalian embryogenesis. The concentration of retinoic acid is extremely low and strictly regulated by enzymes of cytochrome P450 (CYP) family, CYP26s (CYP26A1, CYP26B1 and CYP26C1) in the cells. Therefore, it is thought that changes in CYP26s activities due to exposure to a wide variety of drugs and chemicals exhibit teratogenicity. In this study, to easily detect the changes in retinoic acid level, we constructed an adenovirus-mediated reporter assay system using the promoter region of the CYP26A1 gene and inserting retinoic acid response element (RARE) and retinoid X response element (RXRE) into the downstream of the luciferase gene of reporter plasmid, which highly increased the response to retinoic acid. Reporter activity significantly increased in a concentration-dependent manner with retinoic acid; this increase was also observed at least after treatment with a very low concentration of 1 nM retinoic acid. This increase was suppressed by the accelerated metabolism of retinoic acid due to the overexpression of CYP26A1; however, this suppression was almost completely suspended by treatment with talarozole, a CYP26 inhibitor. In conclusion, the reporter assay system constructed using the induction of CYP26A1 expression is a risk assessment system that responds to extremely low concentrations of retinoic acid and is useful for assessing the excess vitamin A mediated teratogenicity caused by various chemicals at the cellular level.

Optical coherence tomography (OCT) has been used to investigate heart development because of its capability to image both structure and function of beating embryonic hearts. Cardiac structure segmentation is a prerequisite for quantification of embryonic heart motion and function using OCT. Since manual segmentation is time-consuming and labor-intensive, an automatic method is needed to facilitate high-throughput studies. The purpose of this study is to develop an image processing pipeline to facilitate the segmentation of beating embryonic heart structures from a 4-D OCT dataset. Sequential OCT images were obtained at multiple planes of a beating quail embryonic heart and reassembled to a 4-D dataset using image-based retrospective gating. Multiple image volumes at different time points were selected as key-volumes and their cardiac structures including myocardium, cardiac jelly, and lumen were manually labeled. Registration-based data augmentation was used to synthesize additional labeled image volumes by learning transformations between key-volumes and other unlabeled volumes. The synthesized labeled images were then used to train a fully convolutional network (U-Net) for heart structure segmentation. The proposed deep learning-based pipeline achieved high segmentation accuracy with only two labeled image volumes and reduced the time cost of segmenting one 4-D OCT dataset from a week to two hours. Using this method, one could carry out cohort studies that quantify complex cardiac motion and function in developing hearts.

A 61-year-old man presented with retroperitoneal hemorrhage caused by an aneurysm rupture of the pancreaticoduodenal arcade (PDA), and acute celiac artery dissection distal to celiac axis stenosis. Owing to the gradual growth of the false lumen, we planned to deploy a stent to the celiac artery dissection and embolize the PDA aneurysm. Prior to stent placement, we assessed the acute celiac artery dissection distal to the stenosis using four-dimensional computed tomography (CT) angiography through expiration/inspiration/expiration cycle. We diagnosed median arcuate ligament syndrome considering that the celiac axis showed a hooked narrowing at end-expiration, and the compression decreased at end-inspiration. Additionally, the true lumen distal to the stretched axis dilated in the inspiration phase. Therefore, we could advance a catheter into the true lumen during inspiration and successfully deploy a stent. Subsequently, laparoscopic median arcuate ligament release was performed after the stent deployment. A postoperative CT scan showed good patency in the stent, with disappearance of the blood filling the false lumen and with reduced celiac axis stenosis.

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 wk of human gestation), the regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared with controls, whereas embryos given FA with ethanol had significantly reduced regurgitant blood flow but without returning to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions, and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE-induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects are warranted. NEW & NOTEWORTHY State-of-the-art biophotonic tools captured blood flow and endocardial cushion volumes in tiny beating quail embryo hearts, an accessible model for studying four-chambered heart development. Both hemodynamic flow and endocardial cushion volumes were altered with ethanol exposure but normalized when folic acid was introduced with ethanol. Folic acid supplementation preserved hemodynamic function that is intimately involved in sculpting the heart from the earliest stages of heart development.

Optical coherence tomography (OCT) has been used to investigate heart development because of its capability to image both structure and function of beating embryonic hearts. Cardiac structure segmentation is a prerequisite for the quantification of embryonic heart motion and function using OCT. Since manual segmentation is time-consuming and labor-intensive, an automatic method is needed to facilitate high-throughput studies. The purpose of this study is to develop an image-processing pipeline to facilitate the segmentation of beating embryonic heart structures from a 4-D OCT dataset. Sequential OCT images were obtained at multiple planes of a beating quail embryonic heart and reassembled to a 4-D dataset using image-based retrospective gating. Multiple image volumes at different time points were selected as key-volumes, and their cardiac structures including myocardium, cardiac jelly, and lumen, were manually labeled. Registration-based data augmentation was used to synthesize additional labeled image volumes by learning transformations between key-volumes and other unlabeled volumes. The synthesized labeled images were then used to train a fully convolutional network (U-Net) for heart structure segmentation. The proposed deep learning-based pipeline achieved high segmentation accuracy with only two labeled image volumes and reduced the time cost of segmenting one 4-D OCT dataset from a week to two hours. Using this method, one could carry out cohort studies that quantify complex cardiac motion and function in developing hearts.

Drug-induced liver injury (DILI) is one of the major causes for the discontinuation of drug development and withdrawal of drugs from the market. Since it is known that reactive metabolite formation and being substrates or inhibitors of cytochrome P450s (P450s) are associated with DILI, we systematically investigated the association between human P450 inhibition and DILI. The inhibitory activity of 266 DILI-positive drugs (DILI drugs) and 92 DILI-negative drugs (no-DILI drugs), which were selected from Liver Toxicity Knowledge Base (US Food and Drug Administration), against 8 human P450 forms was assessed using recombinant enzymes and luminescent substrates, and the threshold values showing the highest balanced accuracy for DILI discrimination were determined for each P450 enzyme using receiver operating characteristic analyses. The results showed that among the P450s tested, CYP1A1 and CYP1B1 were inhibited by DILI drugs more than no-DILI drugs with a statistical significance. We found that 91% of drugs that showed inhibitory activity greater than the threshold values against CYP1A1 or CYP1B1 were DILI drugs. The results of internal 5-fold cross-validation confirmed the usefulness of CYP1A1 and CYP1B1 inhibition data for the threshold-based discrimination of DILI drugs. Although the contribution of these P450s to drug metabolism in the liver is considered minimal, our present findings suggest that the assessment of CYP1A1 and CYP1B1 inhibition is useful for screening DILI risk of drug candidates at the early stage of drug development.

Autonomous mobile robots are being used to automate many tasks such as cleaning, delivering items, and surveillance. Such tasks often require uninterrupted and continuous service. However, robots have limited battery power and must be recharged frequently. Since manually charging each robot is not always feasible, automatic charging (docking) stations have been developed to automate the process of charging. In a multi-robot system, the tasks are generally distributed between the robots, and different robots have different amounts of remaining battery power. Since the charging stations are expensive, a limited number of charging points are generally available. Hence, an intelligent planner to manage a limited number of charging points for a large number of robots is essential. In this work, we propose a multi-robot path planner for intelligently accessing a limited number of charging points distributed on the map. Unlike traditional path planners, which mainly consider the shortest path criterion to generate paths, the proposed planner also considers the remaining battery power of the robots, task priority, and robot’s location in the map. It allocates the most appropriate charging station to the robots, which require recharging. Simulation results show that the proposed planner can reduce trajectory re-planning, and plan efficient paths to the available charging points.

Pulmonary embolectomy is an effective treatment of acute pulmonary embolism (APE) but not for chronic pulmonary thromboembolism. We described surgical experience of two patients with APE in preexistent unidentified chronic pulmonary thromboembolism. One patient who presented with severe hypoxia but stable hemodynamics underwent successful pulmonary endarterectomy for proximal organized thrombus instead of pulmonary embolectomy. The other patient who required extracorporeal membrane oxygenation for severe hypoxia developed right heart failure because of residual distal organized thrombus after pulmonary embolectomy. Clinical and radiographical presentation of APE in chronic pulmonary thromboembolism mimics APE, and thus, candidates of pulmonary embolectomy should be carefully selected.