Search

Objective: This study reviewed the application of curved and bileaflet designs to pulmonary expanded polytetrafluoroethylene conduits with diameters of 10 to 16 mm and characterized this conduit on in vitro experiment, including particle image velocimetry., Methods: All patients who received this conduit between 2010 and 2022 were evaluated. Three 16-mm conduits were tested in a circulatory simulator at different cardiac outputs (1.5-3.6 L/minute) and bending angles (130°-150°)., Results: Fifty consecutive patients were included. The median operative body weight was 8.4 kg (range, 2.6-12 kg); 10-, 12-, 14-, and 16-mm conduits were used in 1, 4, 6, and 39 patients, respectively. In 34 patients, the conduit was implanted in a heterotopic position. The overall survival rate was 89% at 8 years with 3 nonvalve-related deaths. There were 10 conduit replacements; 5 16-mm conduits (after 8 years) and 1 12-mm conduit (after 6 years) due to conduit stenosis, and the remaining 4 for reasons other than conduit failure. Freedom from conduit replacement was 89% and 82% at 5 and 8 years, respectively. Linear mixed-effects models with echocardiographic data implied that 16-mm conduits were durable with a peak velocity <3.5 m/second and without moderate/severe regurgitation until the patient's weight reached 25 kg. In experiments, peak transvalvular pressure gradients were 11.5 to 25.5 mm Hg, regurgitant fractions were 8.0% to 14.4%, and peak Reynolds shear stress in midsystolic phase was 29 to 318 Pa., Conclusions: Our conduits with curved and bileaflet designs have acceptable clinical durability and proven hydrodynamic profiles, which eliminate valve regurgitation and serve as a reliable bridge to subsequent conduit replacement., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Organisms receive environmental information and respond accordingly in order to survive and proliferate. Temperature is the environmental factor of most immediate importance, as exceeding its life-supporting range renders essential biochemical reactions impossible. In this chapter, we introduce the mechanisms underlying cold tolerance and temperature acclimation in a model organism-the nematode Caenorhabditis elegans, at molecular and physiological levels. Recent investigations utilizing molecular genetics and neural calcium imaging have unveiled a novel perspective on cold tolerance within the nematode worm. Notably, the ASJ neuron, previously known to possess photosensitive properties, has been found to sense temperature and regulate the sperm and gut cell-mediated pathway underlying cold tolerance. We will also explore C. elegans' cold tolerance and cold acclimation at the molecular and tissue levels., (© 2024. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule widely expressed on the surface of cancer cells and is an attractive immunotherapeutic target for numerous cancer cell types. However, patients with endometrial cancer derive little clinical benefit from immune checkpoint blockade therapy because of their poor response rate. Despite the increasingly important function of PD-L1 in tumor immunology, the mechanism of PD-L1 localization on endometrial cancer cell surfaces is largely unknown. We demonstrated the contribution of the ezrin, radixin, and moesin (ERM) family, which consists of scaffold proteins that control the cell surface localization of several transmembrane proteins to the localization of PD-L1 on the cell surface of HEC-151, a human uterine endometrial cancer cell line. Confocal immunofluorescence microscopy and immunoprecipitation analysis revealed the colocalization of all the ERM with PD-L1 on the cell surface, as well as their protein-protein interactions. The RNA-interference-mediated knockdown of ezrin, but not radixin and moesin, significantly reduced the cell surface expression of PD-L1, as measured by flow cytometry, with little impact on the PD-L1 mRNA expression. In conclusion, among the three ERM proteins present in HEC-151 cells, ezrin may execute the scaffold function for PD-L1 and may be mainly responsible for the cell surface localization of PD-L1, presumably via the post-translational modification process.

Background: Indwelling urinary catheters are commonly used in hospitalized patients, which can lead to the development of urinary catheter complications, including catheter-associated urinary tract infection (CAUTI). Limited reports on the appropriateness of urinary catheter use exist in Japan. This study investigated the prevalence and appropriateness of indwelling urinary catheters, and the incidence of CAUTI in non-intensive care unit (non-ICU) wards in Japanese hospitals., Methods: This prospective observational study was conducted in 7 non-ICU wards from 6 hospitals in Japan from October 2017 to June 2018. At each hospital the study teams evaluated urinary catheter prevalence through in-person bedside evaluation for at least 5 days of each week for 3 months. Catheter associated urinary tract infection (CAUTI) incidence and appropriateness of catheter use was collected via chart review., Results: We assessed 710 catheter-days over 5528 patient-days. The mean prevalence of indwelling urinary catheter use in participating wards was 13% (range: 5% to 19%), while the mean incidence of CAUTI was 9.86 per 1000 catheter-days (range: 0 to 33.90). Approximately 66% of the urinary catheter days assessed had an appropriate indication for use (range: 17% to 81%). A physician's order for catheter placement was present in only 10% of catheterized patients., Conclusion: This multicenter study provides epidemiological information about the appropriate use of urinary catheters in Japanese non-ICU wards. A multimodal intervention may help improve the appropriate use of urinary catheters., (© 2022. The Author(s).)

Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions., (© 2021. The Author(s).)

Background: We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis., Methods: Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood., Results: The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice., Conclusions: Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes., (© 2022 Japan Pediatric Society.)

Patients with pancreatic cancer (PC) often suffer from refractory ascites associated with peritoneal metastasis. This severely impairs activities of daily living and leads to an unfavorable prognosis. Cell-free and concentrated ascites reinfusion therapy (CART) has attracted attention as a promising therapy for relieving the symptoms of malignant ascites. Accumulating evidence suggests that malignant ascites contains a variety of soluble factors, such as cytokines, that can be beneficial or detrimental in the prognosis of patients with refractory ascites. However, the expression profiles of these cytokines in the ascites before and after CART remain unknown. In this study, we used a comprehensive cytokine array to measure the expression levels of 102 cytokines in ascites derived from patients with PC before and after CART. The assay results revealed that the concentrations of several cytokines exacerbating tumor angiogenesis and tumor-suppressive interferon-gamma (IFN-γ) and interleukin-12 (IL-12) were higher in ascites after CART than before CART. Interestingly, growth of KP-2 human PC cells following exposure to ascites after CART decreased considerably compared to that before CART. Concomitant treatment of neutralizing antibodies against IFN-γ or IL-12 with ascites after CART restored the growth of KP-2 cells to the control level. These findings indicate that IFN-γ and IL-12 in ascites after CART may contribute to the inhibited growth of PC cells, highlighting their potential as biomarkers for assessing the clinical efficacy of CART procedures in patients with PC.

Caenorhabditis elegans has a simple nervous system of 302 neurons. It however senses environmental cues incredibly precisely and produces various behaviors by processing information in the neural circuit. In addition to classical genetic analysis, fluorescent proteins and calcium indicators enable in vivo monitoring of protein dynamics and neural activity on either fixed or free-moving worms. These analyses have provided the detailed molecular mechanisms of neuronal and systemic signaling that regulate worm responses. Here, we focus on responses of C. elegans against temperature and review key findings that regulate thermotaxis and cold tolerance. Thermotaxis of C. elegans has been studied extensively for almost 50 years, and cold tolerance is a relatively recent concept in C. elegans . Although both thermotaxis and cold tolerance require temperature sensation, the responsible neurons and molecular pathways are different, and C. elegans uses the proper mechanisms depending on its situation. We summarize the molecular mechanisms of the major thermosensory circuit as well as the modulatory strategy through neural and tissue communication that enables fine tuning of thermotaxis and cold tolerance.

Objectives: Cold polypectomy (CP) is widely used because of its safety profile. This systematic review and meta-analysis aimed to clarify the indications for CP based on polyp size., Methods: We searched PubMed and the Cochrane Library for randomized controlled trials that compared cold snare polypectomy (CSP) and other procedures for polyps ≤10 mm. Large-scale prospective observational studies were also searched to assess delayed bleeding rates. The studies were integrated to assess the risk ratio for incomplete resection rates according to polyp size. The Cochrane risk of bias tool was used to evaluate the study bias. The certainty of cumulative evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system., Results: We found 280 articles and reviewed their eligibility. We selected and extracted 12 randomized controlled trials and 3 prospective observational studies. The risk ratio of incomplete resection of polyps ≤10 mm using CSP compared with hot snare polypectomy (HSP) was 1.36 (95% confidence interval [CI], 0.92-2.01). The risk ratio for incomplete removal using CSP compared with cold forceps polypectomy (CFP) was 0.50 (95% CI, 0.31-0.82). For polyps ≤3 mm, the risk ratio of CSP compared with CFP was 1.40 (95% CI, 0.39-4.95). Certainty of cumulative evidence was considered low. No delayed bleeding after CP was reported after the treatment of 3446 polyps., Conclusions: CSP and HSP may result in the same complete resection rates for polyps ≤10 mm. For polyps ≤3 mm, CFP and CSP may have the same resection rates (PROSPERO registration number: CRD42019122132)., Competing Interests: Conflicts of Interest Takuji Kawamura received a research grant from Boston Scientific for the previous study. This meta-analysis was self-funded., (Copyright © 2020 by The Japan Society of Coloproctology.)

Caenorhabditis elegans mechanoreceptors located in ASG sensory neurons have been found to sense ambient temperature, which is a key trait for animal survival. Here, we show that experimental loss of xanthine dehydrogenase (XDH-1) function in AIN and AVJ interneurons results in reduced cold tolerance and atypical neuronal response to changes in temperature. These interneurons connect with upstream neurons such as the mechanoreceptor-expressing ASG. Ca 2+ imaging revealed that ASG neurons respond to warm temperature via the mechanoreceptor DEG-1, a degenerin/epithelial Na + channel (DEG/ENaC), which in turn affects downstream AIN and AVJ circuits. Ectopic expression of DEG-1 in the ASE gustatory neuron results in the acquisition of warm sensitivity, while electrophysiological analysis revealed that DEG-1 and human MDEG1 were involved in warm sensation. Taken together, these results suggest that cold tolerance is regulated by mechanoreceptor-mediated circuit calculation., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

In Japanese pharmaceutical education, the Model Core Curriculum was revised in 2013 to train pharmacists who can appropriately evaluate literature and use evidence-based medicine (EBM). However, in the investigation of EBM education at pharmaceutical universities in 2015, it was found that literature evaluation was hardly performed in the education of undergraduate students. One of the reason is the lack of EBM lecturers at each universities. Therefore, we adopted team-based learning (TBL) to educate more than 50 undergraduate students on the practical evaluation of literatures and the understanding of EBM concepts. The learning outcomes of this strategy were evaluated using the scores of individual tests before and after the class. As a result, the mean scores on the post-test significantly improved from 4.34 to 6.42 out of 10 total points (p<0.001). We further administered a questionnaire survey regarding the understanding of EBM (the mean score was 4.12). In conclusion, it was suggested that TBL for a large number was effective in EBM education for providing knowledge of literature evaluation and the understanding of fundamental concepts.

The high-speed liquid-jet velocity achieved using an injector strongly depends on the piston motion, physical property of the liquid, and container shape of the injector. Herein, we investigate the liquid ejection mechanism and a technique for estimating the ejection velocity of a high-speed liquid jet using a pyro jet injector (PJI). We apply a two-dimensional numerical simulation with an axisymmetric approximation using the commercial software ANSYS/FLUENT. To gather the input data applied during the numerical simulation, the piston motion is captured with a high-speed CMOS camera, and the velocity of the piston is measured using motion tracking software. To reproduce the piston motion during the numerical simulation, the boundary-fitted coordinates and a moving boundary method are employed. In addition, we propose a fluid dynamic model (FDM) for estimating the high-speed liquid-jet ejection velocity based on the piston velocity. Using the FDM, we consider the liquid density variation but neglect the effects of the liquid viscosity on the liquid ejection. Our results indicate that the liquid-jet ejection velocity estimated by the FDM corresponds to that predicted by ANSYS/FLUENT for several different ignition-powder weights. This clearly shows that a high-speed liquid-jet ejection velocity can be estimated using the presented FDM when considering the variation in liquid density but neglecting the liquid viscosity. In addition, some characteristics of the presented PJI are observed, namely, (1) a very rapid piston displacement within 0.1 ms after a powder explosion, (2) piston vibration only when a large amount of powder is used, and (3) a pulse jet flow with a temporal pulse width of 0.1 ms.

Background: Gastrointestinal symptoms, including nausea, vomiting, bowel obstruction, ascites, constipation, and anorexia, are common and often refractory in advanced cancer patients. The palliation of gastrointestinal symptoms is important in improving the quality of life of cancer patients, as well as that of their families and caregivers. Currently published clinical guidelines for the management of gastrointestinal symptoms in cancer patients do not comprehensively cover the topics or are not based on a formal process for the development of clinical guidelines. Methods: The Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of gastrointestinal symptoms in cancer patients after a formal guideline development process. Results: This article summarizes the recommendations along with their rationale and a short summary of the development process of the JSPM gastrointestinal symptom management guidelines. We established 31 recommendations, all of which are based on the best available evidence and agreement of expert taskforce members. Discussion: Future clinical studies and continuous guideline updates are required to improve gastrointestinal symptom management in cancer patients.

Osaka University of Pharmaceutical Sciences has included an evidence-based medicine (EBM) exercise in the introductory education for clinical practice for 4th-year pharmacy students since 2015. The purpose of this exercise is to learn the process of practice and basic concepts of EBM, especially to cultivate the practical ability to solve patients' problems and answer their questions. Additionally, in 2016, we have attempted flipped teaching. The students are instructed to review the basic knowledge necessary for active learning in this exercise by watching video teaching materials and to bring reports summarizing the contents on the flipped teaching days. The program includes short lectures [overview of EBM, document retrieval, randomized controlled trials (RCTs), and systematic review], exercises [patient, intervention, comparison, outcome (PICO) structuring, critical appraisal of papers in small groups with tutors], and presentations. The program includes: step 1, PICO structuring based on scenarios; step 2, critical appraisal of English-language papers on RCTs using evaluation worksheets; and step 3, reviewing the results of the PICO exercise with patients. The results of the review are shared among groups through general discussion. In this symposium, I discuss students' attitudes, the effectiveness of small group discussions using flipped teaching, and future challenges to be addressed in this program.

Practicing evidence-based medicine (EBM) is likely to gain importance for clinical pharmacists in the relatively near future in Japan. An educational program including research and the critical appraisal of literature was required for pharmacy students as of 2015. We organized a six-month practical EBM course for pharmacy students at Hyogo University of Health Sciences. To evaluate its effectiveness, students took a 10-question test after completing the course. The mean score of six students was 8.33±1.79 points. We also conducted a 1-day practical EBM workshop for pharmacists. Changes in knowledge and skills related to EBM were evaluated based on the responses to 10 questions. Knowledge and skills related to several variables improved significantly after the workshop (6.36 points before versus 9.09 points after the workshop; p=0.023). The results suggested that our EBM educational course is effective in improving EBM-related knowledge and skills of pharmacists and pharmacy students.

This study evaluated the effect of an evidence-based medicine (EBM) educational program on EBM-related knowledge and skills of pharmacists and pharmacy students. Our preliminary educational program included the following four sessions: 1) ice breaker, 2) formulation of answerable clinical questions from virtual clinical scenario using the PICO criteria, 3) critical appraisal of the literature using a checklist, and 4) critical appraisal of the results and integrating the evidence with experience and patients values. Change in knowledge and skills related to EBM were evaluated using pre- and post-seminar 4-point scale questionnaires comprising of 14 questions. A total of 23 pharmacists, 1 care manager, and 5 pharmacy students participated in our EBM educational seminar. Knowledge and skills related to several variables improved significantly post-seminar (pre-seminar 2.80 versus 3.26 post-seminar; p<0.001). Specifically, the skills of formulating answerable clinical questions from virtual clinical scenario and critical appraisal of the literature using a checklist improved. Our findings suggested that EBM educational program using problem-based learning was effective in improving EBM-related knowledge and skills of pharmacists and pharmacy students.

The mass transfer across a sheared gas-liquid interface strongly depends on the Schmidt number. Here we investigate the relationship between mass transfer coefficient on the liquid side, k L , and Schmidt number, Sc, in the wide range of 0.7 ≤ Sc ≤ 1000. We apply a three-dimensional semi direct numerical simulation (SEMI-DNS), in which the mass transfer is solved based on an approximated deconvolution model (ADM) scheme, to wind-driven turbulence with mass transfer across a sheared wind-driven wavy gas-liquid interface. In order to capture the deforming gas-liquid interface, an arbitrary Lagrangian-Eulerian (ALE) method is employed. Our results show that similar to the case for flat gas-liquid interfaces, k L for the wind-driven wavy gas-liquid interface is generally proportional to Sc -0.5 , and can be roughly estimated by the surface divergence model. This trend is endorsed by the fact that the mass transfer across the gas-liquid interface is controlled mainly by streamwise vortices on the liquid side even for the wind-driven turbulence under the conditions of low wind velocities without wave breaking.

A 55-year-old Japanese woman was hospitalized because liver function tests showed an abnormality. Transaminases and biliary enzymes were markedly elevated with hyperferritinemia. Her imaging tests revealed no significant abnormality. She had been taking various non-prescription supplements for over approximately 6 months. After the supplements were discontinued her liver function gradually improved. This clinical course was suggestive of supplement-induced hepatitis. She had no history of taking supplements containing iron, so it was interesting that she had hyperferritinemia. We examined C282Y and H63D, which are important mutations in theiron-metabolizing gene, HFE. She was found to be heterozygous for the H63D mutation. The interaction between hyperferritinemia and supplements is unknown, but it can be speculated that some interaction between iron overload and supplements may have underlain the pathogenesis of her liver injury.

Two compounds were synthesized which have a structural component other than those of our new series histone deacetylase (HDAC) inhibitors to determine the structure-activity relationship. It was also examined whether the inhibitory effects on cancer cell proliferation by HDAC inhibitors involve p21/WAF1 induction and G(1) or G(2)/M arrest in p53-mutated MG63 human osteosarcoma cells as do other HDAC inhibitors. It was demonstrated that inhibitors with the 2-naphthylcarbonyl group and hydroxamic acid at both termimal sides as well as the phenylene component at the center of molecule markedly induce the p21/WAF1 protein by stimulating p21/WAF1 gene promoter activity. Furthermore, cell cycle analysis revealed that these compounds arrest MG63 cells in the G(2)/M phase.

Apigenin, a common dietary flavonoid, has been shown to induce cell growth-inhibition and cell cycle arrest in many cancer cell lines. One important effect of apigenin is to increase the stability of the tumor suppressor p53 in normal cells. Therefore, apigenin is expected to play a large role in cancer prevention by modifying the effects of p53 protein. However, the mechanisms of apigenin's effects on p53-mutant cancer cells have not been revealed yet. We assessed the influence of apigenin on cell growth and the cell cycle in p53-mutant cell lines. Treatment with apigenin resulted in growth-inhibition and G2/M phase arrest in two p53-mutant cancer cell lines, HT-29 and MG63. These effects were associated with a marked increase in the protein expression of p21/WAF1. We have shown that p21/WAF1 mRNA expression was also markedly increased by treatment with apigenin in a dose- and time-dependent manner. However, we could not detect p21/WAF1 promoter activity following treatment with apigenin. Similarly, promoter activity from pG13-Luc, a p53-responsive promoter plasmid, was not activated by treatment with apigenin with or without p53 protein expression. These results suggest that there is a p53-independent pathway for apigenin in p53-mutant cell lines, which induces p21/WAF1 expression and growth-inhibition. Apigenin may be a useful chemopreventive agent not only in wild-type p53 status, but also in cancer with mutant p53.

Genistein is the most abundant isoflavone of soybeans and has been shown to cause growth arrest in various human cancer cell lines. However, the precise mechanism for this is still unclear. We report here that the growth arrest and DNA damage-inducible gene 45 (gadd45) gene is induced by genistein via its promoter in a DU145 human prostate cancer cell line. The binding of transcription factor nuclear factor-Y to the CCAAT site of the gadd45 promoter appears to be important for this activation by genistein.

Cyclopentenone prostaglandins (PGs) of the J series, which are produced by dehydration of PGD(2), have been reported to induce apoptosis in various cell lines. One of these cyclopentenone PGs, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)), is the most potent inducer of apoptosis in the series, but the signaling pathways by which it induces apoptosis are poorly understood. We recently reported that cyclopentenone PGs accumulate in the endoplasmic reticulum (ER) and it has been shown that the transcription factor CHOP is induced by ER-stresses and elicits apoptosis. In the present study we demonstrated that 15-d-PGJ(2) induces CHOP mRNA/protein in HeLa cells via activation of the conserved regions in the CHOP promoter. Using several mutants of the CHOP promoter fragments, we found that two regions, CCAAT/enhancer-binding protein (C/EBP) site at -313 and ER-stress element (ERSE) at -93, are involved in activation of the CHOP gene by 15-d-PGJ(2). These results suggest that 15-d-PGJ(2) activates the CHOP promoter in two distinct pathways that could induce apoptosis of HeLa cells.

Silicon rubber peritoneal dialysis catheter (Tenkoff) was inserted perioperatively in neonates undergoing cardiac surgery and also in those patients in whom right-sided heart failure may occur. This method is easy and safe even in neonates. Post operative excessive fluid retention could be avoided using this method.