Collaborative Study of Thresholds for Mutagens: Adaptive Responses in the Micronucleus Test and Gene Induction by Mutagenic Treatments.

Background: We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. Methods: The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. Results: When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner. Conclusion: Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.

The Influence of Micro-Hexapod Walking-Induced Pose Changes on LiDAR-SLAM Mapping Performance.

Micro-hexapods, well-suited for navigating tight or uneven spaces and suitable for mass production, hold promise for exploration by robot groups, particularly in disaster scenarios. However, research on simultaneous localization and mapping (SLAM) for micro-hexapods has been lacking. Previous studies have not adequately addressed the development of SLAM systems considering changes in the body axis, and there is a lack of comparative evaluation with other movement mechanisms. This study aims to assess the influence of walking on SLAM capabilities in hexapod robots. Experiments were conducted using the same SLAM system and LiDAR on both a hexapod robot and crawler robot. The study compares map accuracy and LiDAR point cloud data through pattern matching. The experimental results reveal significant fluctuations in LiDAR point cloud data in hexapod robots due to changes in the body axis, leading to a decrease in map accuracy. In the future, the development of SLAM systems considering body axis changes is expected to be crucial for multi-legged robots like micro-hexapods. Therefore, we propose the implementation of a system that incorporates body axis changes during locomotion using inertial measurement units and similar sensors.

A Case Report of Inhaled Nitric Oxide for Transfusion-Related Acute Lung Injury.

Transfusion-related acute lung injury (TRALI) is an acute respiratory distress syndrome (ARDS) occurring during or within six hours after transfusion. On the other hand, while inhaled nitric oxide (iNO) temporarily improves arterial oxygenation with selective pulmonary vasodilation, there is no evidence of mortality reduction in ARDS. We herein report a case in which TRALI was diagnosed with severe hypoxemia during cardiovascular surgery, and extracorporeal membrane oxygenation (ECMO) was avoided by using iNO for respiratory management. Administering iNO to patients with acute respiratory failure may be useful as a bridging therapy to help patients recover. However, further evidence is needed before this treatment can become standard practise.

Comparison of hemodynamics and root configurations between remodeling and reimplantation methods for valve-sparing aortic root replacement: a pulsatile flow study.

PURPOSE: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator. METHODS: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18). Valve models were tested at mean pulsatile flow and aortic pressure of 5.0 L/min and 120/80 (100) mmHg, respectively, at 70 beats/min. The forward flow, regurgitation, leakage, backflow rates, valve-closing time, and mean and peak pressure gradient (p-PG) were evaluated. Root configurations were examined using micro-computed tomography (micro-CT). RESULTS: The backflow rate was larger in the RM models than in the RI models (RI: 8.56% ± 0.38% vs. RM: 12.64% ± 0.79%; p < 0.01). The RM-AP and RI models were comparable in terms of the forward flow, regurgitation, backflow rates, p-PG, and valve-closing time. The analysis using a micro-CT showed a larger dilatation of the sinus of the Valsalva in the RM groups than in the RI group (Valsalva: RI, 26.55 ± 0.40 mm vs. RM-AP22, 31.22 ± 0.55 mm [p < 0.05]; RM-AP18, 31.05 ± 0.85 mm [p < 0.05]). CONCLUSIONS: RM with ESA and RI with neo-sinuses showed comparable hemodynamics. ESA to RM reduced regurgitation.

Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302.

Introduction: With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC. Methods: Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p = 0.0001), fatigue (5.1% vs. 15.8%, p = 0.0194), malaise (11.1% vs. 25.7%, p = 0.0103), appetite loss (12.1% vs. 28.7%, p = 0.0048), abdominal pain (12.1% vs. 23.8%, p = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, p = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, p = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm. Conclusions: Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.

Use of deep learning to predict postoperative recurrence of lung adenocarcinoma from preoperative CT.

PURPOSE: Although surgery is the primary treatment for lung cancer, some patients experience recurrence at a certain rate. If postoperative recurrence can be predicted early before treatment is initiated, it may be possible to provide individualized treatment for patients. Thus, in this study, we propose a computer-aided diagnosis (CAD) system that predicts postoperative recurrence from computed tomography (CT) images acquired before surgery in patients with lung adenocarcinoma using a deep convolutional neural network (DCNN). METHODS: This retrospective study included 150 patients who underwent curative surgery for primary lung adenocarcinoma. To create original images, the tumor part was cropped from the preoperative contrast-enhanced CT images. The number of input images to the DCNN was increased to 3000 using data augmentation. We constructed a CAD system by transfer learning using a pretrained VGG19 model. Tenfold cross-validation was performed five times. Cases with an average identification rate of 0.5 or higher were determined to be a recurrence. RESULTS: The median duration of follow-up was 73.2 months. The results of the performance evaluation showed that the sensitivity, specificity, and accuracy of the proposed method were 0.75, 0.87, and 0.82, respectively. The area under the receiver operating characteristic curve was 0.86. CONCLUSION: We demonstrated the usefulness of DCNN in predicting postoperative recurrence of lung adenocarcinoma using preoperative CT images. Because our proposed method uses only CT images, we believe that it has the advantage of being able to assess postoperative recurrence on an individual patient basis, both preoperatively and noninvasively.

Collaborative Study of Thresholds for Mutagens: Hormetic Responses in Cell Proliferation Tests Using Human and Murine Lymphoid Cells.

BACKGROUND: We previously showed that hormetic responses can be established in cell activity tests using human and murine adherent cells. This time, we examined whether hormetic responses can be established in cell proliferation tests using suspended human and murine lymphoid cells. METHODS: Human lymphoblastoid cells (TK6) and mouse lymphoma cells (L5178Y) were cultured in multi-well culture plates and treated with mitomycin C, ethyl methansulfonate, hygromycin B, aclarubicin or colchicine at various dose levels and the number of cells was measured at varied times using a flow cytometer. RESULTS: When the ratio of the number of cells treated with a test chemical to those in the negative control was plotted, the dose-response relationship typically showed a reverse U-shaped curve, indicating the occurrence of hormesis and existence of thresholds in cell toxicity. The hormetic responses depended largely on the test chemical, dose level and exposure time. When examining responses over the course of time, a J-shaped or fallen S-shaped curve was also observed. CONCLUSIONS: The dose-response relationship showed a reverse U-shaped curve, a hallmark of hormesis, at least some time points for all chemicals tested here, indicating that chemical hormesis can be established in in vitro cell proliferation tests.

Aortic root geometry following valve-sparing root replacement with reimplantation or remodeling: experimental investigation under static continuous pressure.

The differences in aortic root geometry associated with various valve-sparing root replacement (VSRR) techniques have not fully been understood. We evaluated the root configuration of current VSRR techniques by developing in vitro test apparatus. Six fresh porcine hearts were used for each model. The aortic root remodeling control group involved replacement of the ascending aorta with diameter reduction of sino-tubular junction (STJ) (C1). The aortic valve reimplantation control group involved replacement of the ascending aorta alone (C2). VSRR included remodeling without (RM) or with annuloplasty (RM + A) and reimplantation with a tube (RI) or a handmade neo-Valsalva graft (RI + V). The root geometry of each model in response to closing hydraulic pressures of 80 and 120 mmHg was investigated using echocardiography. Among the VSRR models, RM yielded the largest aorto-ventricular junction (AVJ), which was similar to those in non-VSRR models [mean AVJ diameter (mm) at 80 mmHg; RM = 25.1 ± 1.5, RM + A = 20.9 ± 0.7, RI = 20.7 ± 0.9, RI + V = 20.8 ± 0.4]. RI + V yielded the largest Valsalva size and largest ratio of Valsalva/AVJ, which was similar to the control group [mean Valsalva diameter (mm) at 80 mmHg; RM = 28.4 ± 1.4, RM + A = 25.8 ± 1.3, RI = 23.6 ± 1.0, RI + V = 30.5 ± 0.8, ratio of Valsalva/AVJ at 80 mmHg; RM = 1.14 ± 0.06, RM + A = 1.24 ± 0.06, RI = 1.15 ± 0.06, RI + V = 1.47 ± 0.05]. The STJ diameter at 80 mmHg was numerically smaller with RM + A (22.4 ± 1.2 mm) than with RM (24.8 ± 2.3 mm, p = 0.11). There were no significant differences in AVJ, Valsalva, or STJ distensibility or ellipticity between procedures. Current modifications, including annuloplasty for remodeling or reimplantation in the setting of neo-Valsalva graft, yield near-physiological root geometries.

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

n the original publication, in a title of Table 2.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.

Burden of cardiovascular disease in Japanese cancer patients and survivors: a single cancer-center study in Niigata City.

BACKGROUND: Cardiovascular disease (CVD) and cancer are major causes of death in Japan. As most CVDs are chronic and often aggravate, long-term follow-up is necessary. Although some cancer patients and survivors have CVD, its prognostic significance and prevalence are unknown. Therefore, we conducted a retrospective study at our center to determine the prevalence of cancer patients with CVD. METHODS: In 2015, our 10-year (2005-2014) cancer registry was summarized. Comorbidities including left ventricular dysfunction, atrial fibrillation (AF), ischemic heart disease, aortic stenosis, venous thromboembolism (VTE), and elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were examined. RESULTS: In total, 26,235 de novo cancer patients were registered and 16,130 survived until January 1, 2015. The 5-year survival rate was 64.0% for all cancer patients and 44.2% for cancer patients with CVD. Cox proportional hazards analysis adjusting for age, cancer stage, and body mass index revealed that AF [hazard ratio (HR) 1.219, male; P = 0.038], VTE (HR 1.517, male; P = 0.003 and HR 2.089, female; P < 0.001), and NT-proBNP elevation (HR 1.861, female; P = 0.002) were significantly associated with death. The CVD prevalence among cancer survivors in 2015 was 8.7% vs 3.5% for males vs females. AF was the most common CVD (prevalence: male, 4.0%; female, 1.0%). The prevalence of most CVD in adults increased progressively with age, with male predominance (12.1% for male and 7.5% for female patients in the 80 s age group). CONCLUSIONS: One in 10 elderly cancer survivors has serious CVD. AF, VTE, and heart failure were critical comorbidities. Cardiologists and cancer-care providers should recognize CVD presence and monitor patients closely, providing medications or interventions concurrently with cancer therapy.

Collaborative study of thresholds for mutagens: proposal of a typical protocol for detection of hormetic responses in cytotoxicity tests.

BACKGROUND: According to the linear no-threshold model (LNT), even the smallest amount of radiation is hazardous. Although the LNT is not based on solid data, this hypothesis has been applied to mutagens and carcinogens. As a result, it has been postulated that there are no thresholds for these chemicals. To demonstrate negativity by experiments is practically impossible, because negative data may leave behind the possibility that additional data might make the resolution power high enough to change negativity to positivity. Furthermore, additional data collection may be endless and we may be trapped in agnosticism. When hormesis is established, in which biological responses are higher at low-doses and lower at high-doses than the control, thresholds could be established between the low- and high-doses. Before examination of thresholds in chemical mutagenesis, hormetic responses in cytotoxicity were tested using cultured mammalian cells. METHOD: Human cells (HeLa S3 and TK6) or Chinese hamster cells (CHL/IU) were cultured in 96-well plates and treated with mitomycin C (MMC) or ethyl methanesulfonate (EMS) at various dose levels and optical density was measured after addition of a reagent to detect cellular activity. In hormetic responses, data might fluctuate to and fro; therefore, experimental conditions were examined from various aspects to eliminate confounding factors including cell numbers, detection time, the edge effect of 96-well plates, and measurement time after addition of the reagent for detection. RESULTS: The dose response relationship was never linear. Cellular activities after treatment with MMC or EMS were generally higher at lower doses levels and lower at higher doses than the control, showing hormesis and allowing the establishment of thresholds. Dose response curves sometimes showed two or three peaks, probably reflecting different cellular responses. CONCLUSION: Hormetic responses in cytotoxicity tests were observed and thresholds could be established. Based on the results of this investigation, we put forward a tentative protocol to detect chemical hormesis in cytotoxicity tests, i.e., inoculate 2000 cells per well, add various doses of a test chemical 48 h after inoculation, add a detection dye 10 h after treatment, and measure optical density 2 h after addition of the reagent for detection.

Symptomatic myocardial bridging: a frequently occurring coronary variation can cause severe myocardial ischaemia in affected children with underlying cardiac conditions.

Myocardial bridging is a congenital coronary artery anomaly in which the coronary artery has a partly "tunnelled" intramyocardial course. This tunnelling leads to compression of the affected vessel segment during ventricular systole. It is considered to be a benign variation of the norm in about 25% of the population caused by an aberrancy of embryologic coronary development. The bridging is also thought to cause severe cardiac conditions in a few of those affected. The series of six young patients presented here is the largest series so far to report on symptomatic myocardial bridging in children with different underlying heart diseases. All patients recently presented to our centre with signs of myocardial ischaemia. They subsequently underwent coronary angiography, which revealed myocardial bridging of the ramus interventricularis anterior. In all patients, therapy with ß blockers was started to reduce heart rate and myocardial contractility. ß Blocker treatment was also given in order to prolong diastole and improve coronary artery blood flow. Two patients underwent surgical exposure of the involved coronary segment: a 2-year-old boy because of recurrent, severe myocardial ischaemia in combination with a reduction of general health, changes in ST-segments, and the presence of a dilative cardiomyopathy; and a 13-year-old girl because of evidence of myocardial ischaemia during exercise testing after surviving sudden cardiac death. Surgery was successful and recovery was complete and uneventful. The presented series shows that myocardial bridging can be symptomatic and may require urgent treatment and even surgical intervention in early childhood in rare cases.

[Mitral Valve Repair in a Patient with Two Aneurysms of the Mitral Valve Due to Infective Endocarditis;Report of a Case].

Echocardiography revealed 2 aneurysms in the mitral valve with mitral regurgitation and aortic regurgitation,in a 42-years-old man. He had had infective endocarditis due to Streptococcus 9 months before. A prolapse in the right coronary cusp without vegetation and 2 aneurysms in the anterior mitral leaflet were found intraoperatively. Aortic valve was replaced, and then mitral aneurysms were resected and repaired using his own pericardium. There has been almost no regurgitation or recurrence of infection over 3 years.

Rescue surgery for neonate with huge rhabdomyoma and left outflow obstruction.

We describe a rescue operation in a neonate with a large left ventricular tumor obstructing the left ventricular outflow tract. Surgical resection was performed through an aortotomy and transseptal approach. We excised the main part of the tumor, which was obstructing the outflow tract, leaving a portion that was strongly attached to posterior wall of the left ventricle and mitral valve annulus, which was not feasible to remove. Histological examination showed a rhabdomyoma with benign features. The girl was doing well after 3 months, with no residual tumor growth and no signs of obstruction of the left ventricular outflow tract.

Hepatic arterial infusion chemotherapy using fluorouracil, epirubicin, and mitomycin C for patients with liver metastases from gastric cancer after treatment failure of systemic S-1 plus cisplatin.

BACKGROUND: For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression. PURPOSE: To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin. MATERIAL AND METHODS: We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly). RESULTS: Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months. CONCLUSION: Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC.

Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate-Rapid Tumor Regression Documented by Real Time 3D Echocardiography.

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.

Traumatic sinus of valsalva aneurysm repaired by partial david operation.

We report a case of chronic type A dissection and aneurysm of the sinus of Valsalva after a motor bike accident which remained undetected for 20 years. It was successfully treated with a modified valve-preserving technique. The noncoronary sinus formed a 4.5 × 5.0 cm large and heavily calcified aneurysm, compressing the right atrium and right coronary artery. The pathology was limited to the noncoronary sinus area and here was the annulus dilatated but the remaining sinuses and annulus and the cusps were intact. We have therefore performed a one-third or partial-David procedure with a satisfactory result.