Ultrahigh toughness zirconia ceramics.

The attainment of both high strength and toughness is the ultimate goal for most structural materials. Although ceramic material has been considered for use as a structural material due to its high strength and good chemical stability, it suffers from the limitation of low toughness. For instance, although Y2O3-stabilized tetragonal ZrO2 polycrystals (Y-TZPs) exhibit remarkable toughness among ceramics due to their phase transformation toughening mechanism, this toughness is still much weaker than that of metals. Here, we report Y-TZP-based ceramic materials with toughnesses exceeding 20 MPa m1/2, which is comparable to those of metals, while maintaining strengths over 1,200 MPa. The superior mechanical properties are realized by reducing the phase stability of tetragonal zirconia by tailoring the microstructure and chemistry of the Y-TZP. The proposed ceramic materials can further advance the design and application of ceramic-based structural materials.

[Therapeutic Effect and Adverse Events of Ramucirumab in Patients with Gastric Cancer in Our Hospital].

From January 2016 through December 2017, 18 patients received paclitaxel plus ramucirumab combination therapy and 1 patient received ramucirumab monotherapy. Thus, a total of 19 patients were analyzed in terms of both therapeutic effect and adverse events. The response evaluation of the targeted lesion was as follows; CR: 0, PR: 1, SD: 16, PD: 2. The median of overall survival and progression-free survival of the combination therapy was 9.9 months and 4.2 months, respectively. Although more than half of the patients were enforced after tertiary therapy in our department, the therapeutic effect of paclitaxel plus ramucirumab combination therapy was considerably satisfactory. Neutropenia as an adverse event was observed in 13(68.4%)out of 19 patients, and 8 patients(42.1%)had neutropenia greater than Grade 3. Non -hematologic toxicity was observed in 17 cases(89.5%), and anorexia, nausea, diarrhea, dysgeusia, peripheral neuropathy, hair loss, and fatigue were determined to be either Grade 1 or 2. Alternatively, 1 patient developed Grade 3 interstitial pneumonia, and 3 patients(15.8%)had complicated Grade 3 high blood pressure. Only 2 patients who had severe adverse events, one was interstitial pneumonia and the other was high blood pressure, discontinued paclitaxel plus ramucirumab combination therapy.

Tactile Estimation of Molded Plastic Plates Based on the Estimated Impulse Responses of Mechanoreceptive Units.

This study proposes a tactile estimation method of molded plastic plates based on human tactile perception characteristics. Plastic plates are often used in consumer products. The tactile evaluation plays an important role in product development. However, physical quantities not taking into account human tactile perception have been employed in previous tactile estimation procedures. Hence, in this study, we adopted the vibrational thresholds of the mechanoreceptive units-FA I, FA II, SA I and SA II-for stimuli detection and developed a tactile estimation method for plastic plates that clarified the mechanoreceptive units related to tactile sensation. The developed tactile sensor consists of a base and a silicone rubber pad that contains strain gauges in it. We detected vibration during touch by the sensor and calculated the estimation of the firing values of the cutaneous mechanoreceptors, which are the essential data obtained by humans during tactile perception, in comparison to the amplitude spectrum of the vibration with the threshold amplitude of each mechanoreceptive unit. Simultaneously, we calculated the relationship between the normal and tangential forces recorded while the sensor ran over the samples. As a result of stepwise linear regression analysis using these values as explanatory variables, the evaluation scores for Soft were successfully estimated using the firing value of FA II and the relationship between normal/tangential forces, and the evaluation scores for Rough were estimated using the SA I firing value.

Establishing an Indicator of Hypokalemia in Patients Receiving Anti-Epidermal Growth Factor Receptor Antibodies.

Risk factors for hypokalemia were analyzed in patients who received anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs) at Gifu Municipal Hospital between February 2010 and March 2013. Subjects were 51 patients (27 men and 24 women) with the median age (interquartile range) of 66 (63-72) years. The study period started from the initiation of anti-EGFR MoAbs administration and ended 4 weeks after administration was completed. Patients were categorized into the side effect group if both minimum serum potassium (Min S-K) grade and b grade (pre-treatment S-K grade-Min S-K grade) were B1; otherwise, they were placed into the no side effect group. Univariate analysis for factors to prevent the side effect identified the "concomitant use of hyperkalemia-inducing drugs" to be statistically significant (p=0.010). Multivariate analysis was conducted on factors with a p value of <0.25 in the univariate analysis and on "concomitant use of hyperkalemia-inducing drugs," which was likely to clinically affect S-K decrease, although its p value was >0.25. It showed that "concomitant use of hyperkalemia-inducing drugs" was a significant risk-prevention factor (odds ratio: 0.138, 95% confidence interval[CI]: 0.033-0.581, p=0.007). In conclusion, "concomitant use of hyperkalemia-inducing drugs" is a factor associated with preventing hypokalemia accompanying anti-EGFR MoAbs administration.

The dexmedetomidine concentration required after remifentanil anesthesia is three-fold higher than that after fentanyl anesthesia or that for general sedation in the ICU.

PURPOSE: The general dexmedetomidine (DEX) concentration required for sedation of intensive care unit patients is considered to be approximately 0.7 ng/mL. However, higher DEX concentrations are considered to be required for sedation and/or pain management after major surgery using remifentanil. We determined the DEX concentration required after major surgery by using a target-controlled infusion (TCI) system for DEX. METHODS: Fourteen patients undergoing surgery for abdominal aortic aneurysms (AAA) were randomly, double-blindly assigned to two groups and underwent fentanyl- or remifentanil-based anesthetic management. DEX TCI was started at the time of closing the peritoneum and continued for 12 hours after stopping propofol administration (M0); DEX TCI was adjusted according to the sedation score and complaints of pain. The doses and concentrations of all anesthetics and postoperative conditions were investigated. RESULTS: Throughout the observation period, the predicted plasma concentration of DEX in the fentanyl group was stable at approximately 0.7 ng/mL. In contrast, the predicted plasma concentration of DEX in the remifentanil group rapidly increased and stabilized at approximately 2 ng/mL. The actual DEX concentration at 540 minutes after M0 showed a similar trend (0.54±0.14 [fentanyl] versus 1.57±0.39 ng/mL [remifentanil]). In the remifentanil group, the dopamine dose required and the duration of intubation decreased, and urine output increased; however, no other outcomes improved. CONCLUSION: The DEX concentration required after AAA surgery with remifentanil was three-fold higher than that required after AAA surgery with fentanyl or the conventional DEX concentration for sedation. High DEX concentration after remifentanil affords some benefits in anesthetic management.

Nanocrystalline, ultra-degradation-resistant zirconia: its grain boundary nanostructure and nanochemistry.

Y2O3-stabilized tetragonal ZrO2 polycrystal (Y-TZP) has been known to be an excellent structural material with high strength and toughness since the pioneering study by Garvie et al. in 1975. However, Y-TZP is not considered an environmental or biomedical material because it undergoes an inherent tetragonal-to-monoclinic (T → M) phase transformation in humid or aqueous environment, which leads to premature failure, so-called low-temperature degradation (LTD). In this study, we demonstrate for the first time that this fatal shortcoming of Y-TZP can be resolved by controlling the grain boundary nanostructure and chemical composition distribution in Y-TZP. Nanocrystalline Y-TZP doped with Al(3+) and Ge(4+) ions exhibits no LTD for more than 4 years in hot water at 140 °C, whereas 70% of the tetragonal phase in conventional TZP transforms to the monoclinic phase within only 15 h. This innovative Y-TZP can be fabricated by pressureless sintering at 1200 °C; far below the sintering temperature for conventional Y-TZP. The developed TZP ceramics will be useful in numerous environmental-proofing applications, particularly in the biomedical engineering field.

[Therapeutic outcome and prognosis in S-1+CDDP chemotherapy for advanced gastric cancer--postoperative histopathological assessment].

UNLABELLED: The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (< or =75 y.o.) having type 4/large type 3 (diameter> or = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414). CONCLUSION: These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).

[Percutaneous cryoablation therapy under local anesthesia for unresectable metastatic liver tumors].

Even though liver resection is the first choice against metastatic liver tumors, oncologists are often obliged to include other treatment modalities depending on metastatic tumor size, number of metastatic nodules, location of tumors, patient's general condition, and so on. Among others we selected cryoablation therapy against unresectable tumors and examined its usefulness clinically in 5 patients. Under local anesthesia, the cryoprobe, which was 3 mm in diameter, was introduced into the center of the tumor by use of an ultrasonographic guiding technique. In the middle of the freezing process, through ultrasonography we could clearly monitor the target tumor, which would change into an ice ball. It was noteworthy that not only the treated tumor but also untreated tumors were reduced in 2 cases. Because of extra-hepatic metastases, 3 patients died within 1 year after the therapy, while 2 patients are alive. This modality was easily repeatable and was minimally invasive with little toxic effect. In addition, it did not worsen quality of life (QOL). The above results indicate that cryoablation therapy could be a feasible modality against unresectable metastatic liver tumors.

Evaluation of carcinoembryonic antigen mRNA in living, necrotic, and apoptotic gastric cancer cells by reverse transcriptase-polymerase chain reaction.

PURPOSE: Positive mRNA expression of carcinoembryonic antigen (CEA) is often found in histologically negative lymph nodes, even in early gastric cancer. Therefore, we examined the differences in mRNA expression in MKN45 gastric cancer cells obtained under various cell conditions, namely, living cells, necrosis, and apoptosis, and assessed the possibility of detecting micrometastasis from these results. METHODS: MKN45 cells were cultured with low-dose anticancer drugs (5-fluorouracil (5FU) + cisplatin (CDDP)) or cytokines (tumor necrosis factor alpha (TNFAlpha) + interferon gamma (INFGamma)) to induce apoptosis, or subjected to freezing-thawing to induce necrosis. All the treated cells were stained with propidium iodide and Hoechst and the numbers of living, apoptotic, and necrotic cells were counted. CEA mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and DNA fragmentation was confirmed. RESULTS: mRNA expression of CEA and CEA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) tended to decrease as the apoptotic index (AI) increased in the 5FU + CDDP group. On the other hand, almost no change was seen, even when the AI increased, in the TNFAlpha + IFNGamma group. mRNA expression in the necrotic cells was the almost same as that in the living cells. CONCLUSION: Positive CEA mRNA expression by RT-PCR could suggest the existence of living cancer cells.