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Objective The purpose of this study is to investigate changes in autonomic activities and systemic circulation generated by surgical manipulation or electrical stimulation to the human brain stem. Methods We constructed a system that simultaneously recorded microsurgical field videos and heart rate variability (HRV) that represent autonomic activities. In 20 brain stem surgeries recorded, HRV features and sites of surgical manipulation were analyzed in 19 hypertensive epochs, defined as the periods with transient increases in the blood pressure. We analyzed the period during electrical stimulation to the ponto-medullary junction, performed for the purpose of monitoring a cranial nerve function. Results In the hypertensive epoch, HRV analysis showed that sympathetic activity predominated over the parasympathetic activity. The hypertensive epoch was more associated with surgical manipulation of the area in the caudal pons or the rostral medulla oblongata compared to controls. During the period of electrical stimulation, there were significant increases in blood pressures and heart rates, accompanied by sympathetic overdrive. Conclusions Our results provide physiological evidence that there is an important autonomic center located adjacent to the ponto-medullary junction. Significance A large study would reveal a candidate target of neuromodulation for disorders with autonomic imbalances such as drug-resistant hypertension.

BackgroundAberrant expression of CD70 in several malignancies is potentially associated with poor patient prognosis and could serve as a therapeutic target. However, the clinical relevance of CD70 expression in pancreatic cancer has not been thoroughly explored.MethodsWe evaluated CD70 expression in 166 surgical specimens obtained from human patients with pancreatic cancer. We analyzed the function of CD70 in proliferation and migration using pancreatic cancer cell lines with silenced CD70 expression.ResultsCD70 expression was positively stained in 42 patients (25%). In the whole cohort, high CD70 expression was not associated with overall survival (OS: 33.1 vs. 40.8 months, P = 0.256), although it was significantly associated with inferior OS in a population of patients that completed adjuvant chemotherapy (P = 0.027). Moreover, the incidence of hematogenous metastasis was significantly higher in patients with high CD70 expression than in those with low CD70 expression (P = 0.020). This finding was also statistically significant in multivariate analyses (P = 0.001). In vitro experiments demonstrated that CD70 expression contributed to cancer cell proliferation independently of gemcitabine treatment as well as cell migration. Furthermore, real-time polymerase chain reaction analysis of frozen surgical tissues showed a correlation between the expression of CD70 and mesenchymal markers.ConclusionsCD70 expression in pancreatic cancer might be involved in hematogenous metastasis. Furthermore, our results imply that CD70 overexpression can serve as a novel prognostic factor and a potential therapeutic target in patients who have completed adjuvant chemotherapy.

Although the prognosis of recurrent pancreatic cancer (RPC) is improving with the appearance of new anticancer drugs, prognostic indicators for RPC are still poorly understood. The aim of this study was to evaluate significance of the inflammation-based prognostic score, including modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and Prognostic Nutritional Index (PNI), in patients with RPC.This study reviewed 263 patients of pancreatic ductal adenocarcinoma at our institution between 2006 and 2015. A receiver operating characteristics curve analysis was performed to determine the cut-off values. The prognostic significance of the inflammation-based prognostic scores were evaluated by a multivariate analysis.172 patients (65.4%) who had recurrence was included in this study. The optimal PNI for predicting 1-year survival after recurrence was 40 with higher area under receiver operating characteristics curve value (0.704) in comparison with other inflammation-based prognostic scores. A univariate and multivariate analysis revealed that liver metastasis (P 0.001) and PNI 40 (P 0.001) were independently associated with the survival time after recurrence. When each of the two predictors was counted as one point and the points were calculated for all cases, a good stratified survival curve was obtained, showing the shorter survival in the higher points: median survival times of 2, 1, and 0 points were 4.3, 11.1, and 21.2 months, respectively (P 0.001).Inflammation-based prognostic scores, especially PNI is useful clinical biomarker for predicting the survival time after recurrence in patients with pancreatic adenocarcinoma.

Highlights • There have been few studies of the long-term outcomes of surgically resected intraductal papillary neoplasm of the bile duct (IPNB). • Mucus might be produced even after the R0 resection of IPNB, and frequent cholangitis or jaundice might be occurred. • The biliary tract of the remnant liver after curative resection should be managed carefully for a long time after surgical resection., Introduction Few studies have reported the long-term outcomes of surgical resected intraductal papillary neoplasm of the bile duct (IPNB). Here, we describe the long-term observation and treatment of a case of widespread IPNB. Presentation of case A 57-year-old male was referred to our hospital due to jaundice and dilation of the intrahepatic bile duct. Computed tomography showed dilation and irregularities of the right intrahepatic and extrahepatic bile ducts together with a 3 cm nodule in the common hepatic duct. Peroral cholangioscopy revealed mucinous discharge from the ampulla of Vater, which resulted in a diagnosis of IPNB. A biopsy of the nodule and the bile duct revealed papillary adenoma in all of them. Right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and left hepaticojejunostomy were performed. The nodule was histologically diagnosed as papillary carcinoma in situ, and R0 resection was performed. However, mucus production from the papillary adenoma in the B3 and B4 was observed. We carefully managed the patient's biliary tract by inserting a biliary drainage tube into the segment 2, and he has survived for more than 7 years since the initial treatment. Discussion Mucus might be produced after the surgical resection of IPNB even if s surgical margin was benign. Five-year survival rate of benign IPNB was reported from 85% to 100%. That might be caused by difference of the postoperative management of the biliary tract. Conclusions Careful management of the biliary tract should be performed after surgical resection of IPNB.

In the normal cerebellum, Purkinje cells (PCs) are generated in a zone along the ventricular surface, migrate radially, and align to form a single-cell layer. However, in mice lacking the secreted protein Reelin or its downstream adaptor protein Dab1, the majority of PCs are located ectopically in the deep cerebellar mass. Nonetheless, how Reelin regulates migration and alignment of PCs remains incompletely understood. Reelin has a highly-conserved C-terminal region (CTR), which is required for its full activity. Here, we report an abnormality of the cerebellum in Reelin CTR-lacking knock-in (ΔC-KI) mice. In the ΔC-KI mice, cerebellar formation was largely normal, but some PCs in selected regions were found to be located ectopically and to frequently form clusters. Ectopic PCs contained a higher amount of Dab1 protein and functional Reelin receptors, including mainly very low-density lipoprotein receptor than correctly-aligned PCs. Decreasing Dab1 gene dosage exacerbated mislocalization of PCs and the cerebellar structure in Reelin ΔC-KI mice. These results indicate that ectopic PCs in ΔC-KI mice failed to receive sufficient Reelin signaling en route to their final destinations. Further, we also found that Reelin protein with intact CTR binds preferentially to PCs. Thus, it was suggested that the extent or quality of Reelin/Dab1 signaling that PCs require for correct positioning vary and that Reelin with intact CTR is required for that of a certain subset of PCs.

Microsomal prostaglandin E synthase-1 (mPGES-1) is primarily expressed in granulosa cells (GCs) in the preovulatory follicle. Both prostaglandin E2 (PGE2) and progesterone (P4) are implicated in various reproductive functions. Here, we demonstrate that mPges-1 may be a direct downstream target gene of the P4 receptor and P4-stimulated PGE2 secretion can stimulate P4 production in a newly generated mouse GC line (GtsT). Treatment of GtsT cells with a P4 receptor agonist, norgestrel, markedly increased mPGES-1 expression detected by RT-PCR analysis. PGE2 secretion measured by an enzyme-linked immunosorbent assay was enhanced by P4 treatment. Luciferase assays revealed that the proximal promoter region of the mPges-1 gene was responsible for the effects of P4 treatment. Conversely, PGE2 treatment stimulated P4 secretion, which coordinated with mRNA expression of steroidogenic acute regulatory protein. Taken together, P4 may regulate mPGES-1 expression to increase PGE2 secretion and in turn P4 production. An autocrine loop between P4 and PGE2 might function to maintain the increased levels of both in GCs.

Improvement of proton conductivity of solid electrolyte films needs to form three-dimensional proton conduction paths by controlling the pore size and the pore structure between particles in particle films. A particle assemble method using electrophoretic deposition technique is useful for speedy and mass production assembly. In the electrophoretic deposition method, structure of particle array can be controlled by the electric field. As a result, the proton conductivity of the film showed a higher value for the regularly-arranged particle film and it is increased with a decrease in particle diameter. The proton conductivity of the film with the particles of diameter 50 nm had the highest value. The particle film with the well-controlled structure may enable the fuel cell to be operated in the middle temperature range.

Background Several coronary artery Z score models have been developed. However, a Z score model derived by the lambda-mu-sigma (LMS) method has not been established. Methods Echocardiographic measurements of the proximal right coronary artery, left main coronary artery, proximal left anterior descending coronary artery, and proximal left circumflex artery were prospectively collected in 3,851 healthy children ≤18 years of age and divided into developmental and validation data sets. In the developmental data set, smooth curves were fitted for each coronary artery using linear, logarithmic, square-root, and LMS methods for both sexes. The relative goodness of fit of these models was compared using the Bayesian information criterion. The best-fitting model was tested for reproducibility using the validation data set. The goodness of fit of the selected model was visually compared with that of the previously reported regression models using a Q-Q plot. Results Because the internal diameter of each coronary artery was not similar between sexes, sex-specific Z score models were developed. The LMS model with body surface area as the independent variable showed the best goodness of fit; therefore, the internal diameter of each coronary artery was transformed into a sex-specific Z score on the basis of body surface area using the LMS method. In the validation data set, a Q-Q plot of each model indicated that the distribution of Z scores in the LMS models was closer to the normal distribution compared with previously reported regression models. Finally, the final models for each coronary artery in both sexes were developed using the developmental and validation data sets. A Microsoft Excel–based Z score calculator was also created, which is freely available online (http://raise.umin.jp/zsp/calculator/). Conclusions Novel LMS models with which to estimate the sex-specific Z score of each internal coronary artery diameter were generated and validated using a large pediatric population.