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Background In the field of oncofertility, patients with breast cancer are often administered letrozole as an adjuvant drug before and after oocyte retrieval to prevent an increase in circulating estradiol. Case presentation We report a case of abdominal hemorrhage due to an ovarian rupture in a 29-year-old Japanese patient who restarted letrozole 2 days after an oocyte retrieval procedure in which 14 mature oocytes were retrieved. The patient had sought embryo cryopreservation as a fertility preservation option before undergoing treatment for recurrent breast cancer. A day after restarting letrozole treatment, the patient unexpectedly developed severe abdominal pain. Laparoscopic hemostasis was performed to manage the ovarian swelling and hemorrhage. Conclusions The ovaries can be restimulated by restart letrozole after an oocyte retrieval procedure. Therefore, reproductive-medicine practitioners should understand the potential complications of letrozole administration in such cases and take steps to ensure that they are minimized.

Objectives Pregnancy complicated with ovarian endometrioma is a risk factor for preterm delivery and rupture or infection during pregnancy. This study aimed to clarify the effectiveness and safety of transvaginal aspiration during pregnancy for endometrioma diagnosed in the first trimester. Design This retrospective observational study included 8 pregnant women with endometrioma who underwent transvaginal cyst aspiration at 12–14 weeks (aspiration group) between March 2011–March 2018 and 23 pregnant women with endometrioma who refused aspiration during the same period (observation group). Methods Characteristics of patients were compared in both groups. Safety, feasability and complications of transvaginal cyst aspiration were reported. Complications and obstetrical outcomes were reported and compared in both groups. Results The maximum cyst diameter was 8.9 ± 1.5 cm (mean ± standard deviation) in the aspiration group, which was significantly larger than that in the observation group (4.7 ± 0.2 cm). Four preterm deliveries (17.3%) occurred in the observation group and none in the aspiration group. The emergency cesarean section rate during delivery was 14.2% in the aspiration group and 43.7% in the observation group. Conclusions The aspiration group tended to have lower rate of preterm deliveries and emergency cesarean sections, suggesting that cyst aspiration could be an effective, minimally invasive, and safe management option for endometrioma during pregnancy.

Background Ovarian hyperstimulation syndrome is normally induced by ovarian stimulation drugs. Severe cases of ovarian hyperstimulation syndrome involve complications such as renal failure and thrombosis. Evidence has recently been developed for a method to prevent ovarian hyperstimulation syndrome. Most cases of ovarian hyperstimulation syndrome are of an early-onset type, which occurs shortly after injection of human chorionic gonadotropin. However, late-onset ovarian hyperstimulation syndrome, which occurs in a pregnancy cycle, also requires caution. We report our experience in treating a woman who was transported to our hospital with a severe case of ovarian hyperstimulation syndrome occurring during ovarian stimulation and who was determined to have an ectopic pregnancy. Case presentation Assisted reproductive technology was planned for a 29-year-old nulligravida Japanese woman diagnosed with bilateral fallopian tube obstruction and right-sided hydrosalpinx. On day 1 of controlled ovarian stimulation, the result of her human chorionic gonadotropin urine test was negative, and her serum levels of luteinizing hormone, estradiol, and progesterone were normal. On day 11 of controlled ovarian stimulation, the levels of estradiol and progesterone had risen to 9679 pg/ml and 16 ng/ml, respectively, prompting suspension of controlled ovarian stimulation. Eleven days after controlled ovarian stimulation was suspended, the patient demonstrated ascites that did not improve despite administration of cabergoline, and she was transported to our hospital 2 days after. Late-onset ovarian hyperstimulation syndrome suggested that she was pregnant, and her serum human chorionic gonadotropin level was 27,778 IU/ml. She underwent laparoscopic bilateral salpingectomy and was diagnosed with right tubal pregnancy. Conclusion In an ectopic pregnancy, human chorionic gonadotropin sometimes increases later than in an intrauterine pregnancy. In our patient’s case, endogenous human chorionic gonadotropin following the start of controlled ovarian stimulation may have caused late-onset ovarian hyperstimulation syndrome. The key to early detection of similar cases may be to suspect pregnancy in the event of unexpectedly high progesterone levels during ovarian stimulation.

Introduction The prorenin (PR) receptor [(P)RR] contributes to the regulation of the tissue renin-angiotensin system (RAS) and Wnt signaling, which is involved in embryogenesis and the pathological progression of malignant tumors and diabetes mellitus. Placental (P)RR is significantly upregulated in placental tissues from preeclamptic women. However, because it cannot be examined during pregnancy, the chronological relationship between the acceleration of tissue RAS and the disease state of hypertensive disorder of pregnancy (HDP) has not been reported. In this study, we examined whether chronological changes in placental tissue RAS can be assessed by measuring soluble (P)RR [s(P)RR]. Methods We obtained maternal and umbilical cord blood samples from 517 pregnant women (441 singleton and 76 twin pregnancies). The concentrations of s(P)RR and prorenin (PR) were measured using enzyme-linked immunosorbent assays. Results Multivariate analysis showed that maternal serum s(P)RR levels were significantly higher in patients with HDP or fetal growth restriction (FGR) and were positively correlated with serum PR levels. Furthermore, the maternal s(P)RR level was significantly higher in HDP with severe hypertension and after the onset of HDP. However, maternal s(P)RR levels were not affected by the severity of proteinuria. Serum s(P)RR levels in umbilical cord blood of singleton pregnancies were significantly correlated with gestational week at delivery and PR level. Discussion Maternal serum s(P)RR concentrations may reflect acceleration of tissue RAS in the placenta and blood pressure severity; however, the umbilical serum s(P)RR concentration was not affected by maternal HDP.

This study investigated the prevalence and distribution of anomalies of permanent dentition in the current Japanese population by examining an unbiased sample. We conducted a survey of dental anomalies by mass dental screening at eight high schools in 2012. Participants were all students with permanent dentition. Dental anomalies were classified as hypodontia, supernumerary teeth, peg-shaped teeth, fused teeth, and talon cusps. Students with one or more dental anomalies on oral examination were given a differential diagnosis by three specialists. The final sample comprised 9584 participants (5062 boys, 4522 girls). Hypodontia was present in 372 students (3.88 %) with no significant sex difference (191 boys, 181 girls). Frequent sites were the right or left mandibular second premolar, right or left maxillary second premolar, and right or left maxillary lateral incisor. Supernumerary teeth were observed in three boys (0.06 %) and one girl (0.02 %). Peg-shaped teeth were observed in 74 students (0.77 %; 27 boys, 47 girls), differing significantly between sexes; they were most prevalent among maxillary lateral incisors. Of affected students, 18 students (0.19 %) also had hypodontia (3 boys, 15 girls). Fused teeth were present in two boys (0.04 %) and three girls (0.07 %) (gemination in one boy and fusion in the remaining four students). Sites were limited to maxillary and mandibular central and lateral incisors. Talon cusps were observed in two boys (0.04 %) and four girls (0.09 %). The present survey of a large unbiased sample can be considered to reflect the prevalence and distribution of anomalies of permanent dentition in the current Japanese population.

Summary 1. Nephropathy and elevated plasma aldosterone concentrations (PAC) have been observed in (pro)renin receptor transgenic (TG) rats. In the present study, we hypothesized that PAC and/or mineralocorticoid receptor contribute to the nephropathy of TG rats. To test this hypothesis, the effects of a high-sodium (8% NaCl) diet and heminephrectomy on PAC were examined. 2. Feeding of the high-sodium diet for 12 weeks similarly decreased PAC in TG and wild-type (WT) rats. Heminephrectomy further reduced PAC in TG rats fed a high-sodium diet, but had no effect on PAC in WT rats fed a high-sodium diet. 3. Next, the effects of eplerenone (125 mg/kg per day) and dietary salt restriction (0.36% NaCl diet) on proteinuria and renal morphology were examined in rats fed a high-sodium diet or subjected to heminephrectomy. Both eplerenone and dietary sodium restriction significantly reduced the arterial pressure of TG rats, but had no effect in WT rats. In TG rats, treatment with eplerenone significantly decreased urinary protein excretion, but dietary sodium restriction did not. 4. Nephrin and podocin mRNA levels, as determined by real-time quantitative reverse transcription–polymerase chain reaction, were significantly lower in TG rats than in WT rats. In TG rats, eplerenone treatment significantly increased nephrin mRNA levels, but not podocin mRNA levels. Dietary salt restriction significantly increased mRNA levels of both nephrin and podocin. Although zonula occludens (ZO)-1 mRNA levels were similar in both WT and TG rats, eplerenone treatment significantly decreased ZO-1 mRNA levels in TG rats. 5. The results of the present study suggest that the improvement in proteinuria following eplerenone treatment is independent of its effects on sodium balance and may be mediated by effects on the expression of slit diaphragm proteins.

Background A direct renin inhibitor (DRI) had a benefit in decreasing albuminuria in type 2 diabetic patients having already been treated with angiotensin (Ang) II type 1 receptor blocker (ARB), suggesting that aliskiren may have another effect other than blockade of the traditional renin-angiotensin system (RAS). Recently, prorenin bound to (pro)renin receptor ((P)RR) was found and shown to evoke two pathways; the generation of Ang peptides and the receptor-dependent activation of extracellular signal-related protein kinase (ERK). Because (P)RR is present in the podocytes, a central component of the glomerular filtration barrier, we hypothesized that aliskiren influences the (P)RR-induced two pathways in human podocytes. Methods Human podocytes were treated with 2 nmol/l prorenin in the presence and absence of an angiotensin-converting enzyme inhibitor (ACEi) imidaprilat, an ARB candesartan, a DRI aliskiren, or the siRNA knocking down the (P)RR mRNA and the intracellular AngII levels and the phosphorylation of ERK were determined. Results The expression of (P)RR mRNA of human podocytes was unaffected by the treatment with RAS inhibitors, but decreased by 69% with the siRNA treatment. The basal levels of intracellular AngII and the prorenin-induced increase in intracellular AngII were significantly reduced by aliskiren and siRNA treatment, compared with imidaprilat and candesartan. The prorenin-induced ERK activation was reduced to control level by the siRNA treatment, but it was unaffected by imidaprilat, candesartan, or aliskiren. Conclusions Aliskiren is the most potent inhibitor of intracellular AngII levels of human podocytes among RAS inhibitors, although it is incapable of inhibiting the (P)RR-dependent ERK phosphorylation.

To examine the involvement of (pro)renin receptor in the accelerated organ damage in streptozotocin-induced diabetic male SHRsp, the rats fed a high-salt diet were divided into 5 groups: a group treated with the vehicle, a group treated with 15 mg/kg/day of imidapril (ACEi), a group treated with 60 mg/kg/day of imidapril (High ACEi), a group treated with handle region peptide (HRP), and a group treated with both ACEi and HRP (ACEi+HRP). After 8 weeks, the arterial pressure was similar in the vehicle and HRP groups and decreased in the ACEi-treated groups. The renal angiotensin II content decreased similarly in the groups treated with ACEi and/or HRP. Urinary protein excretion also decreased in the ACEi, High ACEi, and HRP groups and significantly further decreased in the ACEi+HRP group. The heart weight of the ACEi+HRP group was significantly lower than that of any other groups, although the cardiac angiotensin II levels decreased similarly in the groups treated with ACEi and/or HRP. Thus, (pro)renin receptor contributes to the accelerated pathogenesis in the heart and kidneys of diabetic SHRsp.

Numerous in vitro and in vivo animal studies using the (pro)renin receptor (P)RR blocker handle region peptide have suggested an important role of (P)RR in the pathogenesis of end-stage organ damage in patients with diabetes and hypertension. In addition, a limited number of clinical studies have suggested an association between (P)RR gene polymorphisms and blood pressure levels and between (P)RR mRNA levels and angiotensin-converting enzyme mRNA levels in human arteries. However, recent studies have shown that the (P)RR is divided into its soluble form and a residual hydrophobic part, which includes ATPase 6 associated protein 2, within cells. Therefore, the (P)RR may have a more complex function than previously thought. In addition, the physiological roles of the (P)RR remain undetermined, because the construction of (P)RR null mice has not been successful. As a next step for research in this area, a method for determining the soluble (P)RR levels in plasma and urine and the construction of tissue-specific (P)RR-knockout mice are needed to elucidate the roles of the (P)RR in physiology and pathophysiology.

Background/Aims: A significant role of (pro)renin receptor in the pathogenesis of end-organ damage has been suggested only in animal studies. This study was conducted to examine the mRNA expression of (pro)renin receptor in human artery. Methods: In 141 kidney failure patients, the mRNA was harvested from arterial fragments obtained during surgery constructing an arteriovenous access for hemodialysis therapy, and expression levels of (pro)renin receptor and other components of the renin-angiotensin system were determined. Results: Arterial (pro)renin receptor expression was similar in diabetic and non-diabetic patients, although plasma prorenin levels were significantly higher in the diabetic patients than in the non-diabetic patients. The arterial (pro)renin receptor mRNA levels of the hypertensive patients, who had not been treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers, were significantly lower than those of the patients who had been treated with either drug. Multiple regression analyses showed a significant association with a large coefficient between the arterial mRNA level of the (pro)renin receptor and the arterial mRNA level of ACE; this significant association disappeared in patients who had been treated with either drug. Conclusion: (Pro)renin receptor may contribute to the generation of arterial angiotensin II in kidney failure patients.

PURPOSE Little information is available on the mandibular protrusion with oral appliances (OA) for the treatment of obstructive sleep apnea syndrome (OSAS) to have no negative effect on the stomatognathic system. The purpose of the current study was to assess the influence of mandibular protrusion on occlusion to fabricate the appropriate OA. METHODS Twelve healthy adults were selected. With the OA in position, the mandible was advanced 0, 45, 60, 75% of maximum protrusion capacity; bite raising distance between the first molars was 5mm (OA5-0, 45, 60 and 75). The occlusal force, occlusal contact area and occlusal load center following maximum voluntary clenching for 5 seconds were investigated as follows: after wearing the OA for 1, 3 and 6 hours (Stage A1, A3 and A6) and 1 hour after removal (Stage R1). These data were compared with before wearing (Stage B). RESULTS Occlusal force has significant decrement at Stages A1, A3 and A6 after wearing OA5-75, at Stages A3 and A6 after wearing OA5-60, and at Stage A6 after wearing OA5-0. Occlusal contact area has significant decrement at Stages A1, A3 and A6 after wearing OA5-75, and at Stage A6 after wearing OA5-60. Occlusal load center has significant forward displacement at Stages A3 and A6 after wearing OA5-75, and at Stage A6 after wearing OA5-60. CONCLUSION To fabricate the appropriate OA in occlusal perspective, it is preferable to set the mandibular position at 45% advancement of maximum protrusion capacity of condyle head in terms of the mandibular positions used in this study.

The interaction between oral non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone administered concurrently for 30 days was studied in 18 healthy dogs divided into 3 groups of 6 dogs each: a drug-free negative control group (NC group) given 2 gelatin capsules; a group given meloxicam (0.1 mg/kg) and prednisolone (0.5 mg/kg) (MP group); and a group given a reduced dosage of ketoprofen (0.25 mg/kg, p.o.) and prednisolone (0.5 mg/kg, p.o.) (KP group). The dogs were periodically monitored by physical examinations, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests [effective renal plasma flow (ERPF) and glomerular filtration rate (GFR)], urinalyses [urinary sediments, and urinary micro-albumin to creatinine ratio (UAlb/Cre)], urinary enzyme indices, and haemostatic function tests [buccal mucosa bleeding time (BMBT), cuticle bleeding time (CBT)]. Significant changes were observed in the KP group, including a decrease of ERPF and GFR, an increased UAlb/Cre ratio, prolonged BMBT and CBT, as well as the presence of more severe grades of endoscopic lesions and fecal occult blood. In both the MP and KP groups, abnormal enzymuria with exfoliation of renal tubular epithelial cells in the urine was found. However, no significant changes in any of the other tests were observed in the MP group compared with the NC group. These findings suggest that the combination of NSAIDs, even selective COX-2 inhibitors, with prednisolone may be contraindicated due to the potential for serious adverse effects on the kidneys, the platelets, and the gastrointestinal tract.

Background There are many implant cases in which dental technicians take initiative with regard to the design of implant prostheses, and to a certain extent, this area of care is one in which dentists do not necessarily play the leading role. Moreover, inadequate communication between dental technicians and dentists and insufficient instructions for technicians has been highlighted as issues in the past. The purpose of this questionnaire is to improve the quality of implant prostheses and thereby contribute to patient service by clarifying, among other aspects of treatment, problem areas and considerations in the fabrication of implant prostheses, conceptual-level knowledge, and awareness of prosthodontics on the part of the dentists in charge of treatment and methods for preventing prosthetic complications. Methods A cross-sectional survey was given to 120 certified dental technicians. To facilitate coverage of a broad range of topics, we classified the survey content into the following four categories and included detailed questions for (1) the conditions under which implant technicians work, (2) implant fixed prostheses, (3) implant overdentures, and (4) prosthetic complications. Results Out of 120 surveys sent, 74 technicians responded resulting in a response rate of 61.6%. Conclusions This survey served to clarify the current state of implant prosthodontics, issues, and considerations in the fabrication of implant prostheses, and the state of prosthetic complications and preventive initiatives, all from a laboratory perspective. The results of this survey suggested that, to fabricate prostheses with a high level of predictability, functional utility, and aesthetic satisfaction, it is necessary to reaffirm the importance for dentists to increase their prosthetic knowledge and work together with dental technicians to develop comprehensive treatment plans, implement an organized approach to prosthesis design, and accomplish occlusal reconstruction.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.

Objective—To evaluate the safety of reduced-dosage ketoprofen (RDKET) for long-term oral administration in healthy dogs. Animals—14 healthy Beagles. Procedures—Racemic ketoprofen (0.25 mg/kg, PO) and gelatin capsules, as a drug-free placebo, were each administered to 7 dogs for 30 days. Dogs were periodically monitored via physical examination, blood analyses, endoscopic examinations, fecal occult blood tests (tetramethylbenzidine and guaiac methods), renal function tests (effective renal plasma flow and glomerular filtration rate), urinalyses, urinary enzyme indices (N-acetyl-β-D-glucosaminidase and γ-glutamyl-transferase), and hemostatic function tests (buccal mucosa bleeding time, cuticle bleeding time, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration). Results—Pyloric antrum lesion grade was significantly higher in the RDKET group on day 28, compared with the pretreatment and control group grades. Fecal occult blood grade measured by use of the tetramethylbenzidine method was significantly higher in the RDKET group on day 30, compared with the pretreatment grade. No other significant differences were detected between treatment groups. Conclusions and Clinical Relevance—RDKET induced mild to moderate gastric mucosal injuries especially in the pyloric antrum in healthy Beagles, whereas no adverse effects were observed in renal function or hemostasis. Fecal occult blood tests may be useful as screening tests for adverse gastrointestinal effects induced by RDKET in dogs.

To investigate the adverse effects of long-term administration of ketoprofen in dogs, ketoprofen (1 mg/kg) was administered to five clinically healthy beagle dogs (ketoprofen group) and gelatin capsules (control group) were administered to four clinically healthy beagle dogs for 30 days. We monitored the dogs through periodic physical examination, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests, urinalysis, urinary enzyme indices and cuticle bleeding time analysis. The lesions in the stomach, especially in the pyloric antrum, and fecal occult blood progressively worsened in the ketoprofen group. However, the differences between the ketoprofen group and the control group were not statistically significant. One dog in the ketoprofen group temporarily exhibited a decrease in renal plasma flow and two dogs exhibited enzymuria. However, these changes did not persist and the other examinations showed no significant difference between premedication and postmedication in the ketoprofen group. Therefore, the adverse effects of long-term administration of ketoprofen observed in this study were not clinically important in healthy dogs. Nevertheless, further investigation of adverse renal effects from long-term administration of ketoprofen is necessary in the dogs with subclinical renal disease.

Objective: An association between the renin-angiotensin system and the pathogenesis of pregnancy-induced hypertension has been reported. The prorenin receptor was discovered in 2002, and Wanatabe et al. reported that women with plasma soluble prorenin receptor concentrations above the 75th percentile at delivery had a significantly increased risk of preeclampsia. We evaluated serum prorenin concentrations during pregnancy, and we assessed the incidence of pregnancy-induced hypertension. Methods: We measured serum prorenin concentrations in 430 pregnant women (565 samples). Regression analysis was performed to determine the associations between the serum prorenin level and maternal/neonatal complications. Results: The serum prorenin concentration and gestational age had a positive correlation in non-pregnancyinduced hypertension in women with singleton pregnancies (Spearman rank-correlation coefficient, -0.215: p

The handle region peptide (HRP), a (pro)renin receptor (P)RR blocker, did not prevent the acute nephropathy occurring 2 weeks after clipping in renovascular hypertensive rats. This study was performed to examine the effects of HRP, its scramble peptide, or a saline vehicle on slowly progressive nephropathy occurring in the kidneys of two-kidney, one-clip Goldblatt hypertensive rats. At 2 weeks after clipping, the renal morphology in the clipped and non-clipped kidneys was similar in the three groups of rats. At 12 weeks after clipping, however, the glomerulosclerosis index (GI) and the tubulointerstitial damage (TD) of the non-clipped kidneys of the HRP-treated rats were significantly lower than those of vehicle-treated rats, although the GI and the TD were similar in the rats treated with scramble peptide and vehicle. The GI and the TD of the clipped kidneys were similar in the three groups of rats at 12 weeks after clipping. In the non-clipped kidneys at 12 weeks after clipping, activated prorenin levels, angiotensin II levels and transforming growth factor (TGF)-β mRNA levels of HRP-treated rats were significantly lower than those of vehicle-treated rats, although they were similar in the non-clipped kidneys from the rats treated with scramble peptide and vehicle. In the clipped kidneys at 12 weeks after clipping, activated prorenin levels, angiotensin II levels and TGF-β mRNA levels were similar in the three groups of rats. These results suggest that the ((P)RR)-dependent activation of prorenin contributes to the pathogenesis of slowly progressive nephropathy in the intact kidney in a rat model of renovascular hypertension.

Since renin inhibition interferes with the first and rate-limiting steps in the renin–angiotensin system, the renin step is a very attractive target for lowering blood pressure and minimizing target-organ damage. The newly developed direct renin inhibitor aliskiren has several attractive characteristics: it definitively reduces plasma renin activity among inhibitors of the renin–angiotensin system, is remarkably specific for human renin, exhibits a long half-life in plasma comparable to that of amlodipine, and has a high affinity for renal glomeruli and vasculature. Although these characteristics suggest the clinical usefulness and safety of aliskiren, several problems remain unsolved. Why does aliskiren have beneficial effects on the heart and kidneys of patients treated with angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II type 1–receptor blockers (ARBs)? Is the blood-pressure–lowering effect of aliskiren dependent on the plasma renin activity? Does aliskiren exert a possible adverse effect via (pro)renin receptor–dependent intracellular signals? Here, we review the characteristics and usefulness of aliskiren and discuss the current issues associated with this direct renin inhibitor. Keywords:: diabetes, hypertension, kidney, plasma renin activity, (pro)renin receptor, angiotensin

Rationale : The (pro)renin receptor [(P)RR], encoded in ATP6AP2 , plays a key role in the activation of local renin-angiotensin system (RAS). A truncated form of (P)RR, termed M8.9, was also found to be associated with the vacuolar H + -ATPase (V-ATPase), implicating a non–RAS-related function of ATP6AP2. Objective : We investigated the role of (P)RR/ATP6AP2 in murine cardiomyocytes. Methods and Results : Cardiomyocyte-specific ablation of Atp6ap2 resulted in lethal heart failure; the cardiomyocytes contained RAB7- and lysosomal-associated membrane protein 2 (LAMP2)-positive multivesicular vacuoles, especially in the perinuclear regions. The myofibrils and mitochondria remained at the cell periphery. Cardiomyocyte death was accompanied by numerous autophagic vacuoles that contained undigested cellular constituents, as a result of impaired autophagic degradation. Notably, ablation of Atp6ap2 selectively suppressed expression of the V O subunits of V-ATPase, resulting in deacidification of the intracellular vesicles. Furthermore, the inhibition of intracellular acidification by treatment with bafilomycin A1 or chloroquine reproduced the phenotype observed for the (P)RR/ATP6AP2-deficient cardiomyocytes. Conclusions : Genetic ablation of Atp6ap2 created a loss-of-function model for V-ATPase. The gene product of ATP6AP2 is considered to act as in 2 ways: (1) as (P)RR, exerting a RAS-related function; and (2) as the V-ATPase-associated protein, exerting a non–RAS-related function that is essential for cell survival.

Persuasive conversational agents persuade users to change their attitudes or behaviors through conversation and are expected to be applied as virtual sales-clerks in e-shopping sites. Developing such an agent requires a conversation model that identifies the most appropriate responses to the user's inputs. To create such a model, we propose the approach of combining a learning agent with the Wizard of Oz method; in this approach, a person (called the Wizard) talks to the user pretending to be the agent. The agent learns from the conversations between the Wizard and the user and constructs its own conversation model. In this approach, the Wizard has to reply to most of the user's inputs at the beginning, but the burden gradually falls because the agent learns how to reply as the conversation model grows. Every persuasive conversation has the goal of persuading the user and ends with success or failure. We introduce a goal-oriented conversation model that can represent the success probability of persuasion and a learning method to update the model depending on the success/failure of the persuasive conversation. We introduce a learning persuasive agent that implements the conversation model and the learning method and evaluate it in the situation wherein the agent persuades users to choose one type of digital camera over another. The agent could succeed in reducing the Wizard's inputs by 48%, and, more interestingly, succeeded in persuading 2 users without any help from the Wizard.

Objectives An association between the renin-angiotensin system and the pathogenesis of pregnancy-induced hypertension has been reported. The prorenin receptor was discovered in 2002, and Wanatabe et al. reported that women with plasma soluble prorenin receptor concentrations above the 75th percentile at delivery had a significantly increased risk of preeclampsia. We evaluated plasma prorenin concentrations during pregnancy, and we assessed the incidence of pregnancy-induced hypertension. Methods We measured plasma prorenin concentrations in 430 pregnant women (565 samples). Regression analysis was performed to determine the associations between the plasma prorenin level and maternal/neonatal complications. Results The plasma prorenin concentration and gestational age had a positive correlation in non-pregnancy-induced hypertension in women with singleton pregnancies (Spearman rank-correlation coefficient, −0.215; p p p = 0.0107). Conclusions The plasma prorenin levels during pregnancy may be adversely correlated with the prorenin receptor, and low prorenin levels during late pregnancy were significantly associated with pregnancy-induced hypertension. Disclosures Y. Mikami: None. T. Narita: None. Y. Takai: None. K. Baba: None. H. Seki: None. K. Matsuoka: None.

Even in the case of implant loss, replacement of the implant and refabrication of the superstructure are often sufficient, as long as the bone and soft tissue are in good condition. However, if implant loss accompanied by serious bone resorption occurs with a fixed implant superstructure supported by multiple implants, it is very difficult to treat. This clinical report describes the process by which multiple implant-supported fixed metal ceramic restorations were repaired with a metal ceramic resin-bonded fixed partial denture without complete refabrication after removal of one of the implants due to severe bone resorption. The 3-year follow-up indicated excellent serviceability and a well-satisfied patient.

The prorenin receptor is an accessory subunit of the vacuolar H(+)-ATPase, suggesting that it has fundamental functions beyond activation of the local renin-angiotensin system. Podocytes express the prorenin receptor, but its function in these cells is unknown. Here, podocyte-specific, conditional, prorenin receptor-knockout mice died of kidney failure and severe proteinuria within 4 weeks of birth. The podocytes of these mice exhibited foot process effacement with reduced and altered localization of the slit-diaphragm proteins nephrin and podocin. Furthermore, the podocytes contained numerous autophagic vacuoles, confirmed by enhanced accumulation of microtubule-associated protein 1 light chain 3-positive intracellular vesicles. Ablation of the prorenin receptor selectively suppressed expression of the V(0) c-subunit of the vacuolar H(+)-ATPase in podocytes, resulting in deacidification of intracellular vesicles. In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function.