Computational model predicts the neural mechanisms of prepulse inhibition in Drosophila larvae.

Prepulse inhibition (PPI) is a behavioural phenomenon in which a preceding weaker stimulus suppresses the startle response to a subsequent stimulus. The effect of PPI has been found to be reduced in psychiatric patients and is a promising neurophysiological indicator of psychiatric disorders. Because the neural circuit of the startle response has been identified at the cellular level, investigating the mechanism underlying PPI in Drosophila melanogaster larvae through experiment-based mathematical modelling can provide valuable insights. We recently identified PPI in Drosophila larvae and found that PPI was reduced in larvae mutated with the Centaurin gamma 1A (CenG1A) gene, which may be associated with autism. In this study, we used numerical simulations to investigate the neural mechanisms underlying PPI in Drosophila larvae. We adjusted the parameters of a previously developed Drosophila larvae computational model and demonstrated that the model could reproduce several behaviours, including PPI. An analysis of the temporal changes in neuronal activity when PPI occurs using our neural circuit model suggested that the activity of specific neurons triggered by prepulses has a considerable effect on PPI. Furthermore, we validated our speculations on PPI reduction in CenG1A mutants with simulations.

Severe Inflammatory Idiopathic Multicentric Castleman's Disease Coexisting with Advanced Renal Cancer: A Case Report.

The present case study was conducted on a 74-year-old man who visited our department due to a left renal and retroperitoneal tumor on computed tomography (CT). The patient was diagnosed with left renal cancer lymph node metastasis and was hospitalized a few weeks prior to surgery due to fever, malaise, and severe appetite loss. Biochemical laboratory findings at admission showed markedly high levels of inflammation. The cause of high inflammatory response was paraneoplastic syndrome. Tumor resection was considered necessary, and left nephrectomy and lymphadenectomy were performed; however, it did not improve the inflammatory response. After operation, positron emission tomography-CT revealed hyperaccumulation of 18F-fluorodeoxyglucose in the bone marrow throughout the body. Pathological examination of the resected specimen and bone marrow aspiration revealed the coexistence of idiopathic multicentric Castleman disease (CD) and renal cancer. Prednisolone and tocilizumab were administered for idiopathic multicentric CD and a tyrosine kinase inhibitor for renal cancer; however, they had poor therapeutic effect, and the patient died. CD is characterized by systemic symptoms due to the overproduction of interleukin-6. Treatment for idiopathic multicentric CD involves steroid and anti-interleukin-6 therapy. The diagnostic criteria for CD require the exclusion of malignant tumors although there are some cases in which CD and malignant tumors coexist. The prognosis for CD is relatively good; however, as in this case, the prognosis of CD coexisting with uncontrollable renal cancer is insufficient due to poor improvement in the inflammatory response.

Surgery to Avoid Stoma Construction in Invasive Prostate Cancer Extensively Infiltrating the Rectum.

A 61-year-old man tested positive for occult urinary and fecal occult blood and was diagnosed with invasive prostate cancer extensively infiltrating the rectum. After scrutiny, he was diagnosed with cT4N1M0 prostate cancer, and androgen deprivation therapy (ADT) was initiated with a gonadotropin-releasing hormone antagonist. A prostatic rectal resection was performed 6 months after ADT began. The bladder and urethra were anastomosed, the anus was preserved intact, and the sigmoid colon was anastomosed to the anus. A temporary ileostomy was constructed to allow eating and to prevent fistula formation. The ileostomy was closed 5 months post-operation as the patient wanted to live without a stoma. Although the patient died of other disease factors, he remained untreated for 1 year and 7 months post-operation, and his symptoms and disease control were well supported. We report that we were able to perform stoma-free surgical treatment for prostate cancer extensively infiltrating rectum.

Combination Therapy of Pembrolizumab plus Axitinib for a Patient on Hemodialysis with Metastatic Renal Cell Carcinoma: A Case Report.

Here, we discuss the safety and management of adverse events associated with pembrolizumab plus axitinib combination therapy for metastatic renal cell carcinoma in patients on hemodialysis. A 76-year-old man was diagnosed with cT3aN0M0 renal cell carcinoma due to gross hematuria. Stereoscopic radiotherapy for metastatic lesions of the ipsilateral kidney was performed 9 years after right laparoscopic radical nephrectomy. Soon after, the patient started to receive hemodialysis due to end-stage renal disease. Further stereoscopic radiotherapy was needed for metastasis of the ipsilateral kidney and lung. Fifteen years after diagnosis, systemic therapy was necessary to control new metastases, such as in the right scapular bone. We selected pembrolizumab plus axitinib combination therapy as the first-line systemic therapy for any risk as defined by the International Metastatic RCC Database Consortium. Although we needed to pay attention to the adverse events unique to hemodialysis, he underwent this combination therapy without any difficulty for 6 months. Here, we report the practice of combination therapy in patients on hemodialysis in light of the literature.

[A Case of Upper Urinary Tract Stone in an Infant].

A 238-day-old female infant (122 days of age corrected for prematurity, weight 4,847 g) presented with macrohematuria. She was born at 23 weeks and3 days of pregnancy. Her birth weight was 492 g. Ultrasound revealeda 3×2 mm left ureteral stone and left hydronephrosis of grade I-II in the Society of Fetal Urology (SFU) Classification. She suffered from frequent vomiting and weight loss, and was treated with analgesics and rehydration. Eventually, left hydronephrosis was relieved, and she passed the stone at 271 days of age. The stone was 4×3×2 mm in size, and consisted of 98% calcium oxalate and2% calcium phosphate. No recurrent stone has been found during follow-up.

[A Case of Testicular Tumor with Multiple Metastasis Leading to Complete Response after Treatment Interruption].

A 39-year-old man experiencing cranial nerve symptoms was referred to our neurosurgery department after a brain tumor was detected on computed tomography (CT) scans at a local hospital. Due to convulsive symptoms, the patient was admitted to our hospital for detailed examination. The patient was diagnosed with right testicular tumor, multiple brain metastases, multiple lung metastases and right kidney metastases, and was transferred to our urology department. Since the testicular tumor was staged as IIIC and identified as poor prognosis by the International Germ Cell Consensus classification (IGCCC), Bleomycin Etoposide Cisplatin (BEP) chemotherapy was initiated prior to surgery. A right high orchiectomy was performed after two courses of BEP chemotherapy. Histopathology revealed mixed germ cell tumors (seminoma and/or embryonal carcinoma+teratoma) along with the following results : ly (-) ; Intratubular Malignant Germ Cells (ITMGC) (+, viable) ; tunica albuginea invasion (-) ; spermatic cord invasion (-) ; tumor size (73× 50×45 mm). Two additional courses of BEP chemotherapy and two courses of Paclitaxel Ifomaide Cisplatin(TIP) chemotherapy were performed successively. The CT revealed metastatic lesions shrinking steadily but the metastatic foci still remained. Since tumor markers were not negative, continuous chemotherapy was considered. However, strong side effects were expected, and treatment was discontinued. Since then,the tumors continued to shrink, and the tumor markers became negative. Currently, the patient maintains complete response and is being followed-up.

Familial testicular germ cell tumors in two brothers.

INTRODUCTION: Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. CASE PRESENTATION: An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. CONCLUSION: Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

Intraoperative hypothermia is a significant prognostic predictor of radical cystectomy especially for stage II muscle-invasive bladder cancer.

The objective of this study was to evaluate intraoperative hypothermia as a predictor of complication and prognosis in patients with muscle-invasive bladder cancer treated with radical cystectomy.The data of 124 patients treated with radical cystectomy for muscle-invasive bladder cancer in our department, from 2003 to 2016, were retrospectively collected. The patients were divided into 2 groups according to the lowest intraoperative deep body temperature, that is, the hypothermia group (<96.8°F) and the normothermia group (≥96.8°F). Preoperative and intraoperative variables were compared among the 2 groups, and factors associated with complications, recurrences, and survivals were analyzed.Sixty-eight (54.8%) of the 124 patients presented intraoperative hypothermia. There was no significant difference in the patient's characteristics between the 2 groups. Postoperative complications (Clavien-Dindo ≤III) of any types occurred in 15 patients (22.1%) in the hypothermia group, as compared with 8 patients (14.3%) in the normothermia group (P = .27). The hypothermia group had a higher pathologic stage (P = .029) and a higher recurrence rate within 12 months (P = .013), as compared with the normothermia group. Intraoperative hypothermia was an independent prognostic factor for overall survival in all patients (hazard ratio [HR] 2.47; 95% confidence interval [CI], 1.01-2.85; P = .047). When stratified by disease stage, stage II intraoperative hypothermia was an independent prognostic factor for disease-free survival (HR 3.35; 95% CI, 1.27-8.83; P = .015) and overall survival (HR 4.24; 95% CI, 1.38-12.9; P = .011).This study suggests that intraoperative hypothermia could be a significant predictor for recurrence and survival in muscle-invasive bladder cancer treated with radical cystectomy.

Semantic Mapping Based on Spatial Concepts for Grounding Words Related to Places in Daily Environments.

An autonomous robot performing tasks in a human environment needs to recognize semantic information about places. Semantic mapping is a task in which suitable semantic information is assigned to an environmental map so that a robot can communicate with people and appropriately perform tasks requested by its users. We propose a novel statistical semantic mapping method called SpCoMapping, which integrates probabilistic spatial concept acquisition based on multimodal sensor information and a Markov random field applied for learning the arbitrary shape of a place on a map.SpCoMapping can connect multiple words to a place in a semantic mapping process using user utterances without pre-setting the list of place names. We also develop a nonparametric Bayesian extension of SpCoMapping that can automatically estimate an adequate number of categories. In the experiment in the simulation environments, we showed that the proposed method generated better semantic maps than previous semantic mapping methods; our semantic maps have categories and shapes similar to the ground truth provided by the user. In addition, we showed that SpCoMapping could generate appropriate semantic maps in a real-world environment.

[PHEOCHROMOCYTOMA CRISIS WITH MIBG SCINTIGRAPHY NEGATIVE: A CASE REPORT].

We report a case of pheochromocytoma crisis with negative MIBG scintigraphy. A 48-year-old man was admitted for hypertension crisis. Computed tomographic scan revealed a 60 mm right adrenal mass. The MIBG scintigraphy was negative, but we diagnosed pheochromocytoma crisis because of high blood catecholamine levels. We successfully managed the patient's hemodynamics through medical treatment and the patient was able to recover from the crisis. After appropriate preparation, the tumor was removed via laparotomy. SDHB mutation, related to the negative MIBG scintigraphy, was also denied pathologically by immunostaining procedures. Histopathologically, it showed a wide range of necrotic images. So the cause of the crisis was thought to be the release of a large amount of catecholamine from necrotic tumor cells. It was thought that scintigraphy became negative due to the decreased MIBG uptake of tumor cells with extensive necrosis.

Effectiveness of bioengineered islet cell sheets for the treatment of diabetes mellitus.

BACKGROUND: The present study aimed to evaluate whether bioengineered mouse islet cell sheets can be used for the treatment of diabetes mellitus. METHODS: Isolated mouse pancreatic islets were dispersed, and cells were plated on temperature-responsive culture plates coated with iMatrix-551. On day 3 of culture, the sheets were detached from the plates and used for further analysis or transplantation. The following parameters were assessed: (1) morphology, (2) expression of ß-cell-specific transcription factors and other islet-related proteins, (3) methylation level of the pancreatic duodenal homeobox-1 (Pdx-1) promoter, as determined by bisulfite sequencing, and (4) levels of serum glucose after transplantation of one or two islet cell sheets into the abdominal cavity of streptozotocin-induced diabetic severe combined immunodeficiency mice. RESULTS: From each mouse, we recovered approximately 233.3 ± 12.5 islets and 1.4 ± 0.1 × 105 cells after dispersion. We estimate that approximately 68.2% of the cells were lost during dispersion. The viability of recovered single cells was 91.3 ± 0.9%. The engineered islet cell sheets were stable, but the messenger RNA levels of various ß-cell-specific transcription factors were significantly lower than those of primary islets, whereas Pdx-1 promoter methylation and the expression of NeuroD, Pdx-1, and glucagon proteins were similar between sheets and islets. Moreover, transplantation of islet cell sheets did not revert serum hyperglycemia in any of the recipient mice. CONCLUSIONS: Engineering effective islet cell sheets require further research efforts, as the currently produced sheets remain functionally inferior compared with primary islets.

Territory holders and non-territory holders in Ayu fish coexist only in the population growth process due to hysteresis.

Ayu fish form feeding territories during a non-breeding (growing) season. When the density of the fish increases, phases gradually change. In the early growing season, all fish can hold territories at low density. Once all territory sites are occupied, newcomers become floaters. As the density further increases, territory holders have to spend much more time in defending their own territory and lose the time to feed on algae. Eventually, all fish give up their own territories and then form a school. In contrast, when the density decreases, territories are directly reformed from the school. In short, ayu fish exhibit a different transition, called hysteresis, where the two transitions occur widely-apart from each other. The dynamics of this intrinsic phenomena has not been demonstrated in previous studies. We develop a rate equation to describe the population dynamics within territorial competition. Our model successfully reproduces territorial hysteresis and indicates that territory holders and floaters can coexist only in the process of population growth. Moreover, we also find that the two critical densities of territorial hysteresis are conspicuously different from each other when the increase of the density of floaters sharply influences (step-function-like) the territories.

The promotion of cooperation by the poor in dynamic chicken games.

The evolution of cooperative behavior is one of the most important issues in game theory. Previous studies have shown that cooperation can evolve only under highly limited conditions, and various modifications have been introduced to games to explain the evolution of cooperation. Recently, a utility function basic to game theory was shown to be dependent on current wealth as a conditional (state) variable in a dynamic version of utility theory. Here, we introduce this dynamic utility function to several games. Under certain conditions, poor players exhibit cooperative behavior in two types of chicken games (the hawk-dove game and the snowdrift game) but not in the prisoner's dilemma game and the stag hunt game. This result indicates that cooperation can be exhibited by the poor in some chicken games. Thus, the evolution of cooperation may not be as limited as has been suggested in previous studies.

[Availability of Local Therapy to Castration-Resistant Prostate Cancer for M0 Patients with Initial Prostate Specific Antigen 100 ng/ml or Higher].

Prostate cancer patients with initial PSA 100 ng/ml or greater who received transrectal ultrasoundguided prostate biopsy and were staged as M0 by imaging studies from 2011 to 2014 in seven hospitals, were enrolled in the study. Castration-resistant prostate cancer (CRPC)-free survival was compared between the two treatment groups : androgen deprivation therapy (ADT) alone and ADT plus local therapy. Of 142 prostate cancer patients with initial PSA 100 ng/ml or greater, 49 (34.5%) had no metastases and final analysis was performed on 46 patients. Thirty one M0 patients received ADT alone, and 15 received ADT plus local therapy. During follow-up (median 31 months, range 1-56 months) 13 patients (42%) in the ADT alone group progressed to CRPC. One- and two-year CRPC-free survival rates were 72.5 and 53%, respectively. No patients with ADT plus local therapy developed CRPC, and time to CRPC was prolonged significantly (p=0.002). On multivariate analysis for the group with ADT alone, PSA nadir of more than 0. 2 ng/ml and cN1 were independent predictors for progression to CRPC (p=0.009, 0.031). About one third of prostate cancer patients with initial PSA 100 ng/ml or greater had clinically no metastases. Local therapy to prostate combined with ADT may prolong time to CRPC compared with ADT alone. A subset of men with a PSA nadir of more than 0.2 ng/ml after ADT and cN1 could benefit from local therapy.

What Is True Halving in the Payoff Matrix of Game Theory?

In game theory, there are two social interpretations of rewards (payoffs) for decision-making strategies: (1) the interpretation based on the utility criterion derived from expected utility theory and (2) the interpretation based on the quantitative criterion (amount of gain) derived from validity in the empirical context. A dynamic decision theory has recently been developed in which dynamic utility is a conditional (state) variable that is a function of the current wealth of a decision maker. We applied dynamic utility to the equal division in dove-dove contests in the hawk-dove game. Our results indicate that under the utility criterion, the half-share of utility becomes proportional to a player's current wealth. Our results are consistent with studies of the sense of fairness in animals, which indicate that the quantitative criterion has greater validity than the utility criterion. We also find that traditional analyses of repeated games must be reevaluated.

Bonding strength of autopolymerizing resin to nylon denture base polymer.

This study aimed to investigate the shear bond strength of an autopolymerizing resin to a nylon denture base polymer (Lucitone FRS: LT) subjected to different surface treatments, and the results thereof compared with a heat-polymerizing resin and a polycarbonate polymer. Specimens were divided into five groups according to the surface treatment method: polishing (#600), sandblasting, adhesive primer application (resin primer), sandblasting + adhesive primer application, and tribochemical coating (Rocatec system). Following which, specimens were subjected to a shear bond strength test and Si concentrations were measured using an electron probe microanalyzer (EPMA). On shear bond strength, that of LT with tribochemical coating was significantly higher than the other groups. On EPMA results, the surface of LT with tribochemical coating was found to be covered with a silica film. Therefore, findings in this study indicated that silica-coating by Rocatec system was effective in improving the bond strength of nylon denture base polymer to autopolymerizing repair resin.

Influence of simplified silica coating method on the bonding strength of resin cement to dental alloy.

This study evaluated the effectiveness of a simplified silica coating method (CoJet System) on the bonding strength of resin cements to dental alloy. Bonding strength of the specimens treated with metal primer after alumina sandblasting was compared with those treated with silica coating and silane coupling agent after alumina sandblasting. Furthermore, the influence of silane coupling agent on bonding strength was compared between one-liquid and two-liquid silane coupling agents. Measurement of shear bond strength before and after thermal cycling revealed that the group treated with silica coating in one step without alumina sandblasting yielded high bonding strength. As for the influence of silane coupling agent, treatment with two-liquid silane coupling agent achieved higher mean shear bond strength than with one-liquid silane coupling agent. Findings in this study indicated that silicatization by means of this simplified silica coating method was effective in improving the bonding strength to dental alloy.

A study of the effects of irradiation on the polymerization of dual-cured self-etching bonding system using electron spin resonance (ESR) spectroscopy.

The purpose of this study was to investigate the effect of irradiation on the polymerization behavior of a bonding agent of a dual-cured self-etching bonding system. By means of electron spin resonance spectroscopy, it was shown that the concentration of polymer radicals in samples cured chemically without irradiation was closely similar to that in samples dual-cured under irradiation. There was no significant difference in the time required to reach the maximum spin concentration between these two sample groups, thereby showing that the radical generation rates were similar. Findings of this study revealed that the dual-cured self-etching bonding system tested in this study was effective in polymerization in regions where irradiated light could hardly reach.