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Background/purpose Fibroblast growth factor-2 (FGF-2) regulates bone formation. The concept of guided bone regeneration using a resorbable collagen membrane (RCM) is generally accepted in implant dentistry. This study aimed to investigate the bone healing pattern in rat mandibular bone defects in real-time with and without RCM containing FGF-2 (RCM/FGF-2). Materials and methods Critical-size circular bone defects (4.0 mm diameter) were created on both sides of the rat mandibular bone. The defects were randomly divided into the following groups: control, RCM alone, RCM containing low (0.5 μg) or high (2.0 μg) concentration of FGF-2. We performed real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. At 6 weeks, the mandibular specimens were assessed histologically and histomorphometrically to evaluate the area of new bone regeneration. Results Real-time assessment revealed a significant increase in the volume, BMD, and closure percentage of the NFB area in the RCM/FGF-2-treated groups than that in the control and RCM groups. In the H-FGF-2 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks than that at the baseline. Histological evaluation revealed the presence of osteoblasts, osteocytes, and blood vessels within the NFB. Conclusion The real-time in vivo experiment demonstrated that RCM/FGF-2 effectively promoted bone regeneration within the critical-size mandibular defects in rats and verified new bone formation starting in the early postoperative phase.

A control architecture for robust biped navigation that takes into account traversability on terrain, foot-reachability, and capturability all at once in dynamic situations is proposed. It consists...

This paper proposes a robust biped control to track the desired foot-placements, which is suitable to locomotion in complex environments. A strategy to determine the referential ZMP based only on t...

In a 75-year-old hemodialysis patient, pneumonia manifested with computed tomography (CT) images suggestive of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) was not detected with repeated polymerase chain reaction (PCR) tests, but serum immunoglobulin G (IgG) and IgM antibodies against SARS-CoV-2 turned positive with two different assay kits. The patient was thus treated as a probable COVID-19 case, and then recovered through the intensive care including ciclesonide, favipiravir, and methyl prednisolone. In PCR-negative cases, the diagnosis of COVID-19 cannot be established at present, but such COVID-19 cases certainly exist. To avoid a delay in treatment of COVID-19, available diagnostic tools should be utilized with careful attention for their limitations.

A new control architecture for real-world-oriented robots is presented. Awareness of the issue lies in the conventional subsumption architecture, in which outputs from multiple layers often conflict with each other and a naive prioritization of the upper layer by an override of the lower layer reduces the system responsivity against accidental events. The proposed architecture fundamentally avoids such a conflict in a way that the upper-layers modify functions of the lower layers through modulations of internal parameters in them and make the sole output from the bottom layer adapt to situations. This architecture provides a design criterion of each unit function module such that it accepts incomplete and noisy information from the upper-layer modules asynchronously. Simultaneous exploration and navigation (SEAN) system for a biped robot was implemented based on the architecture and evaluated on a computer simulation.

Background. While the evaluation of burr speed was discussed regarding platelet aggregation, the association between platform speed and acute lumen gain of rotational atherectomy remains unknown. Methods. Through the evaluation of the potential of low-speed rotational atherectomy (LSRA) in in-vitro experiments, minimum lumen diameter (MLD) and minimum lumen area (MLA) after conventional high-speed rotational atherectomy (HSRA group) and those after LSRA following HSRA (LSRA+HSRA group) treated by 1.5 mm burrs were measured by optical frequency domain imaging (OFDI) in 30 consecutive human lesions. Results. The in-vitro experiments demonstrated that MLD and MLA after LSRA+HSRA were significantly larger (MLD: LSRA+HSRA=1.50 ±0.05 mm, HSRA= 1.43 ±0.05 mm, p=0.015; MLA: LSRA+HSRA= 1.90 ±0.17 mm2, HSRA= 1.71±0.11 mm2, and p= 0.037), requiring more crossing attempts (LSRA= 134 ±20 times, HSRA= 72 ±11 times, and p< 0.001). In human studies, there was no significance in reference vessel diameter and lesion length before the procedure between two groups. MLDs after LSRA+HSRA were significantly larger than those in HSRA (LSRA+HSRA= 1.22 ±0.16 mm, HSRA= 1.07 ±0.14 mm, and p= 0.0078), while MLAs after LSRA+HSRA tended to be larger (LSRA+HSRA= 1.79 ±0.51 mm2, HSRA= 1.55 ±0.47 mm2, and p= 0.19). There was no significance in the occurrence of in-hospital complication, including slow flow or no reflow, major dissection, and procedural myocardial infarction, between LSRA+HSRA and HSRA. Conclusions. LSRA can achieve larger lumen gain compared, whereas HSRA can pass calcified lesions easily. Combination of LSRA and HSRA is a safe and feasible strategy for severely calcified lesions in clinical practice.

OBJECTIVES To evaluate the effectiveness of the proximal optimization technique (POT) to prevent longitudinal stent elongation. BACKGROUND The mechanism of stent elongation, which occurs after post-balloon dilation, is still unclear. METHODS A total of 103 lesions treated with optical coherence tomography guided coronary intervention between May 2013 and November 2017 were retrospectively analyzed. Lesions were divided according to the circumferential degree of malapposition at the stent edge immediately after deployment into well-apposed group (

The effect of estrogen deficiency in bone augmentation, and the mechanisms by which estrogen deficiency impedes osteoblast differentiation and collagen matrix production, were examined. Twenty female Jcl:Wistar rats were divided into two groups: ovariectomized rats; and control rats. Guided bone augmentation was performed by positioning plastic caps in the calvarium of all animals at 8 wk after ovariectomy or sham surgery. Micro-computed tomography and histological sections were used to determine the amount of bone augmentation within the plastic caps. At 8 wk, there was statistically significantly less newly formed bone volume in ovariectomized rats. Immunohistological staining revealed the rare alignment of runt-related transcription factor 2-positive osteoblast-like cells and collagen I-positive bundle fibers in ovariectomized rats. In cell culture experiments, pre-osteoblast-like cells, MC3T3-E1, were treated with the estrogen receptor antagonist, fulvestrant. In treated cells, alkaline phosphatase activity remained high, whereas Alizarin Red staining was completely inhibited. Extracellular staining intensity of collagen I was decreased after fulvestrant treatment. Consistent with these observations, gene-expression analysis confirmed that fulvestrant treatment led to weaker expression of mRNA for osteogenic transcription factors and bone matrix protein-related genes. The results demonstrate that estrogen deficiency suppresses osteoblast differentiation and collagen matrix production in bone augmentation.

The present study was designed to compare the bone augmentation ability of absorbable collagen sponge (ACS) with that of hydroxyapatite/collagen composite (HAP/Col) using a rat calvaria defect model. Bone defects were created artificially on the surface of the calvariae of 10-week-old male Fisher rats, and then cylindral plastic caps filled with ACS or HAP/Col were placed on the defects. This area was designated as the region of interest (ROI) and new bone formation was observed at 0, 4, 8, and 12 weeks after surgery using micro-CT. Histological examinations were performed using sections obtained from 12-week-old rats. Prominent new bone formation was observed in the HAP/Col group relative to the ACS group; onset of new bone augmentation was evident from 4 weeks after surgery in the HAP/Col group and from 8 weeks in the ACS group. Histological examination revealed that the entire area of the cap was filled with newly formed bone intermingled with the HAP/Col composite. Bone mineral density in the HAP/Col group was double that in the ACS group. These results indicate that the use of HAP/Col contributes significantly to new bone augmentation.

Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus. Moreover, CFSD group had higher oligodendrocytic levels of tryptophan, and impaired spatial cognitive memory accuracy and increased hyperactivity and impulsivity. These findings suggest that dynamic change in glial-neuronal interactions within the hypothalamus-hippocampal circuit causes central fatigue, and increased tryptophan-kynurenic acid pathway activity in this circuit causes reduced cognitive function. Additionally, CFSD group had 1.5 times higher plasma levels of tryptophan and kynurenine. Furthermore, in rats undergoing intraperitoneal administration of kynurenine (100mg/kg) versus vehicle, kynurenine-treated rats showed enhanced production of kynurenic acid in the hippocampus, with suppressed recall of retained spatial cognitive memory. The study revealed that uptake of periphery-derived kynurenine and tryptophan into the brain enhances kynurenic acid production in the brain, and the three factors produce amplification effect involved in the role of central-peripheral linkage in central fatigue, triggering cognitive dysfunction.

Objectives To investigate the accuracy of digital rectal examination in estimating prostate volume in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Methods A community-based study was carried out in Japan to investigate the prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. A total of 457 men were screened and deemed eligible for the present analysis. Findings on digital rectal examination were compared with prostate volume measurement by transrectal ultrasound. Five groups were identified on digital rectal examination: flat, normal, slightly enlarged, moderately enlarged and markedly enlarged. Results The median age and prostate volume were 64 years and 19.7 mL, respectively. Prostate volumes for the flat, normal, slightly enlarged, moderately enlarged, and markedly enlarged groups were 16.4, 18.3, 27.0, 41.9 and 86.3 mL, respectively. There were significant differences in prostate volume between the groups. The positive predictive value was 94.1% if flat, and normal were assumed to have a prostate volume

OBJECTIVES The aim of this study was to investigate the impact of intensively lowered low-density lipoprotein cholesterol (LDL-C) level on the deferred lesion prognosis after revascularization deferral based on fractional flow reserve (FFR). BACKGROUND Lowering LDL-C is associated with lower cardiovascular event rate, but its benefit on the deferred lesion prognosis has not been well evaluated. METHODS This retrospective, single-center, observational study analyzed 192 deferred lesions with FFR value >0.80 in 192 patients with stable coronary artery disease. According to the first follow-up LDL-C level, they were assigned to the LOW group (

We used radiological and histological analyses to evaluate the effects of mechanical barrier permeability in a rat model of calvarial guided bone augmentation (GBA). The calvaria of 20 rats were exposed, and one of four types of plastic caps (an occlusive cylindrical plastic cap; a plastic cap with no top; a plastic cap with three holes; and a plastic cap with four holes) was randomly placed on both sides. Newly generated bone in the plastic caps was evaluated with micro-computed tomography (micro-CT) and histological analysis. Micro-CT volumetric analysis and decalcified hematoxylin and eosin-stained sections showed that GBA barrier permeability was inversely associated with the quantity of augmented bone obtained. Masson's trichrome staining showed that collagen in newly generated bony tissue was more mature in plastic caps with three holes than in those with more-permeable or more-occlusive barriers. Bone augmentation was inhibited in specimens exhibiting invasion of soft tissue through penetrating holes, and barrier permeability was associated with the quantity of augmented bone developed. In conclusion, moderate barrier permeability is optimal for development of mature augmented bone.

Background— Heart failure is accompanied by changes in cardiac metabolism characterized by reduced fatty acid (FA) utilization. However, the underlying mechanism and its causative involvement in the progression of heart failure are poorly understood. The peroxisome proliferator activated receptor-α (PPARα)/retinoid X receptor (RXR) heterodimer promotes transcription of genes involved in FA metabolism through binding to the PPAR response element, called direct repeat 1 (DR1). Silent information regulator 1 (Sirt1) is a histone deacetylase, which interacts with PPARα. Methods and Results— To investigate the role of PPARα in the impaired FA utilization observed during heart failure, genetically altered mice were subjected to pressure overload. The DNA binding of PPARα, RXRα, and Sirt1 to DR1 was evaluated with oligonucleotide pull-down and chromatin immunoprecipitation assays. Although the binding of PPARα to DR1 was enhanced in response to pressure overload, that of RXRα was attenuated. Sirt1 competes with RXRα to dimerize with PPARα, thereby suppressing FA utilization in the failing heart. DR1 sequence analysis indicated that the typical DR1 sequence favors PPARα/RXRα heterodimerization, whereas the switch from RXRα to Sirt1 takes place on degenerate DR1s. Sirt1 bound to PPARα through a region homologous to the PPARα binding domain in RXRα. A short peptide corresponding to the RXRα domain not only inhibited the interaction between PPARα and Sirt1 but also improved FA metabolism and ameliorated cardiac dysfunction. Conclusions— A change in the heterodimeric partner of PPARα from RXRα to Sirt1 is responsible for the impaired FA metabolism and cardiac dysfunction in the failing heart.

Background— In general, Ras proteins are thought to promote cardiac hypertrophy, an important risk factor for cardiovascular disease and heart failure. However, the contribution of different Ras isoforms has not been investigated. The objective of this study was to define the role of H- and K-Ras in modulating stress-induced myocardial hypertrophy and failure. Methods and Results— We used H- and K-Ras gene knockout mice and subjected them to pressure overload to induce cardiac hypertrophy and dysfunction. We observed a worsened cardiac phenotype in Hras −/− mice, while outcomes were improved in Kras +/− mice. We also used a neonatal rat cardiomyocyte culture system to elucidate the mechanisms underlying these observations. Our findings demonstrate that H-Ras, but not K-Ras, promotes cardiomyocyte hypertrophy both in vivo and in vitro. This response was mediated in part through the phosphoinositide 3-kinase-AKT signaling pathway. Adeno-associated virus–mediated increase in AKT activation improved the cardiac function in pressure overloaded Hras null hearts in vivo. These findings further support engagement of the phosphoinositide 3-kinase-AKT signaling axis by H-Ras. Conclusions— Taken together, these findings indicate that H- and K-Ras have divergent effects on cardiac hypertrophy and heart failure in response to pressure overload stress.

Tryptophan (TRP) and its neuroactive metabolite, kynurenic acid (KYNA), are thought to play key roles in central fatigue, but the specifics are still unknown. To clarify their roles in the brain, we developed a rat model of central fatigue induced by chronic sleep disorder (CFSD) by disturbing the sleep-wake cycle. Results showed that while 5-hydroxytryptamine (5-HT) concentration did not differ between control and CFSD groups, levels of TRP and KYNA in the CFSD group were about 2 and 5 times higher in the hypothalamus, and 2 and 3.5 times higher in the hippocampus, respectively. Moreover, CFSD-induced fatigue led to abnormal running performance (via treadmill test) and social interaction (via social-interaction test). These results support a TRP-KYNA hypothesis in central fatigue in which increased TRP concentration in the brain and subsequently synthesized KYNA may produce an amplified effect on central fatigue, with enhanced concentrations being a possible mechanism by which social-interaction deficits are generated.

Purpose Guided bone regeneration (GBR) is the most widely used technique to regenerate and augment bones. Even though augmented bones (ABs) have been examined histologically in many studies, few studies have been conducted to examine the biological potential of these bones and the healing dynamics following their use. Moreover, whether the bone obtained from the GBR procedure possesses the same functions as the existing autogenous bone is uncertain. In particular, little attention has been paid to the regenerative ability of GBR bone. Therefore, the present study histologically evaluated the regenerative capacity of AB in the occlusive space of a rat guided bone augmentation (GBA) model. Methods The calvaria of 30 rats were exposed, and plastic caps were placed on the right of the calvaria in 10 of the 30 rats. After a 12-week healing phase, critical-sized calvarial bone defects (diameter: 5.0 mm) were trephined into the dorsal parietal bone on the left of the calvaria. Bone particles were harvested from the AB or the cortical bone (CB) using a bone scraper and transplanted into the critical defects. Results The newly generated bone at the defects' edge was evaluated using micro-computed tomography (micro-CT) and histological sections. In the micro-CT analysis, the radiopacity in both the augmented and the CB groups remained high throughout the observational period. In the histological analysis, the closure rate of the CB was significantly higher than in the AB group. The numbers of cells positive for runt-related transcription factor 2 (Runx2) and tartrate-resistant acid phosphatase (TRAP) in the AB group were larger than in the CB group. Conclusions The regenerative capacity of AB in the occlusive space of the rat GBA model was confirmed. Within the limitations of this study, the regenerative ability of the AB particulate transplant was inferior to that of the CB particulate transplant., Graphical Abstract

Yap1 is an important regulator of cardiomyocyte proliferation and embryonic heart development, yet the function of endogenous Yap1 in the adult heart remains unknown. We studied the role of Yap1 in maintaining basal cardiac function and in modulating injury after chronic myocardial infarction (MI). Cardiomyocyte-specific homozygous inactivation of Yap1 in the postnatal heart (Yap(F/F)Cre) elicited increased myocyte apoptosis and fibrosis, dilated cardiomyopathy, and premature death. Heterozygous deletion (Yap(+/F)Cre) did not cause an overt cardiac phenotype compared with Yap(F/F) control mice at base line. In response to stress (MI), nuclear Yap1 was found selectively in the border zone and not in the remote area of the heart. After chronic MI (28 days), Yap(+/F)Cre mice had significantly increased myocyte apoptosis and fibrosis, with attenuated compensatory cardiomyocyte hypertrophy, and further impaired function versus Yap(+/F) control mice. Studies in isolated cardiomyocytes demonstrated that Yap1 expression is sufficient to promote increased cell size and hypertrophic gene expression and protected cardiomyocytes against H(2)O(2)-induced cell death, whereas Yap1 depletion attenuated phenylephrine-induced hypertrophy and augmented apoptosis. Finally, we observed a significant decrease in cardiomyocyte proliferation in Yap(+/F)Cre hearts compared with Yap(+/F) controls after MI and demonstrated that Yap1 is sufficient to promote cardiomyocyte proliferation in isolated cardiomyocytes. Our findings suggest that Yap1 is critical for basal heart homeostasis and that Yap1 deficiency exacerbates injury in response to chronic MI.

Objectives Osteogenic protein-1 (OP-1) has shown osteoinductive activities and is useful for clinical treatments, including bone regeneration. Regenerative procedures using a bioabsorbable collagen membrane (BCM) are well established in periodontal and implant dentistry. We evaluated the subsequent effects of the BCM in combination with OP-1 on bone regeneration in a rat mandibular circular critical-sized bone defect in vivo. Design We used 8 rats that received surgery in both sides of the mandible, and created the total 16 defects which were divided into 4 groups: Group 1; no treatment, as a control, Group 2; BCM alone, Group 3; BCM containing low dose 0.5 μg of OP-1 (L-OP-1), and Group 4; BCM containing high dose 2.0 μg of OP-1 (H-OP-1). Newly formed bone was evaluated by micro computed tomography (micro-CT) and histological analyses at 8 weeks postoperatively. In quantitative and qualitative micro-CT analyses of the volume of new bone formation, bone density, and percentage of new bone area was evaluated. Results BCM with rhOP-1 significantly increased and accelerated bone volume, bone mineral density, and percentage of new bone area compared to control and BCM alone at 8 weeks after surgery; these enhancements in bone regeneration in the OP-1-treated groups were dose-dependent. Conclusions OP-1 delivered with a BCM may have effective osteoinductive potency and be a good combination for bone regeneration. The use of such a combination device for osteogenesis may result in safer and more predictable bone regenerative outcomes in the future.

Purpose A multicenter phase I/II study of transarterial chemoembolization with a fine cisplatin powder and gelatin particles (GPs) for multifocal hepatocellular carcinoma (HCC) was conducted. Primary endpoints were dose-limiting toxicity (DLT) and recommended dose (RD). Secondary endpoints were the incidence and severity of adverse events and tumor response. Materials and Methods Nonselective transarterial chemoembolization was performed until all tumor enhancement disappeared. Lipiodol was not used. In the phase I study, the cisplatin dose was escalated from 35 mg/m 2 to 65 mg/m 2 in 15-mg/m 2 increments to determine DLT and RD. In the phase II study, 40 patients were treated with the RD. Toxicity was assessed by Common Toxicity Criteria for Adverse Effects (version 3.0), and tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) and European Association for the Study of the Liver (EASL) criteria. Results A total of 46 patients were enrolled. As no DLT occurred at any dose level in the phase I study, RD was determined as 65 mg/m 2 . In the phase II study, the treatment was discontinued in one patient as a result of vasovagal response. Toxicities of grade 3 or higher included nausea (2.2%), pancreatitis (2.2%), cholecystitis (2.2%), thrombocytopenia (8.7%), hyperbilirubinemia (2.2%), and increased aspartate aminotransferase (28.3%) and alanine aminotransferase (21.7%) levels. Tumor response rates under RD were 25.6% and 64.1% by RECIST and EASL criteria, respectively. Conclusions Nonselective transarterial chemoembolization with fine cisplatin powder and GPs was well tolerated and effective in patients with multifocal HCC at the RD of 65 mg/m 2 .

Purpose:Serotonin, a neurotransmitter synthesized from tryptophan, has been proposed to play a key role in central fatigue. In this study, we examined whether tryptophan itself and/or its two metabolites, kynurenic acid (KYNA) and quinolinic acid (QUIN), are involved in central fatigue.Materials and Methods:Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase analbuminemic rats (NAR). Central fatigue was assessed by treadmill running and a Morris water maze test. Microdialysis was used to collect samples for measurement of extracellular concentration of tryptophan, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) and to infuse test agents. To examine the kinetics of release, synaptosomes in the striatum were prepared in vitro to measure intra- and extrasynaptosomal concentration of tryptophan, serotonin and 5-HIAA.Results:The concentration of tryptophan secreted into the extracellular space of the striatum was higher during fatigue only, and quickly returned to basal levels with recovery from fatigue. Running time to exhaustion was reduced by activation of tryptophan receptors. Time to exhaustion was shorter in NAR, which maintain a higher extracellular level of striatum tryptophan than SDR. Impaired memory performance in a water maze task after tryptophan treatment was attributable to high levels of KYNA and QUIN in the hippocampus acting synergistically on N-methyl-D-aspartic acid receptors. When branched-chain amino acids were administered, tryptophan transport to the extracellular space of the striatum was drastically inhibited.Conclusion:Our findings demonstrate that the increase in fatigue which occurs because of excessively elevated brain tryptophan can be further amplified by the use of synthetic KYNA and QUIN.

SummaryHigh energy production in mitochondria is essential for maintaining cardiac contraction in the heart. Genes regulating mitochondrial function are commonly downregulated during heart failure. Here we show that both PPARα and Sirt1 are upregulated by pressure overload in the heart. Haploinsufficiency of either PPARα or Sirt1 attenuated pressure overload-induced cardiac hypertrophy and failure, whereas simultaneous upregulation of PPARα and Sirt1 exacerbated the cardiac dysfunction. PPARα and Sirt1 coordinately suppressed genes involved in mitochondrial function that are regulated by estrogen-related receptors (ERRs). PPARα bound and recruited Sirt1 to the ERR response element (ERRE), thereby suppressing ERR target genes in an RXR-independent manner. Downregulation of ERR target genes was also observed during fasting, and this appeared to be an adaptive response of the heart. These results suggest that suppression of the ERR transcriptional pathway by PPARα/Sirt1, a physiological fasting response, is involved in the progression of heart failure by promoting mitochondrial dysfunction.

Accumulating lines of evidence suggest that glycogen synthase kinase-3β (GSK-3β) is involved in aging. However, the effects of GSK-3β on cardiac aging and the underlying mechanisms remain to be elucidated. Autophagy, a protective mechanism in aging, decreases with age. We hypothesized that GSK-3β attenuates cardiac aging via Ulk1, a regulator of autophagy, and studied constitutively active GSK-3βS9A knock-in mice (βKI), GSK-3βS9A/Ulk1+/- bigenic mice (Bigenic), and GSK-3β+/- mice (βKO) up to 24 months (M) of age. Left ventricular (LV) weight/body weight (LVW/BW, mg/g) was not significantly different among wild-type mice (WT), βKI and βKO at 6M. It was lower in βKI (2.4±0.1, p

A 10-year-old boy presented with a painless left scrotal mass that had been present for 2 years. Ultrasound examination revealed 2 left testes measuring 2.4 ml and 1.0 ml with the same echogenicity. Atsurgery, there were 2 similarly sized testes connecting with other spermatic vascular, but the supernumerary testis had no connection with the vas deferens. Histological findings showed immature testicular tissue without malignancy. We report the 26th case of polyorchidism in Japan and discuss this condition.

Peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor, plays an important role in the transcription of genes involved in fatty acid metabolism through heterodimerization with the retinoid x receptor (RXR). The consensus sequence of the PPAR response element (PPRE) is composed of two AGGTCA-like sequences directionally aligned with a single nucleotide spacer. PPARα and RXR bind to the 5’ and 3’ hexad sequences, respectively. However, the precise sequence definition of the PPRE remains obscure, and thus, the consensus sequence currently available remains AGGTCANAGGTCA with unknown redundancy. The vague PPRE sequence definition poses an obstacle to understanding how PPARα regulates fatty acid metabolism. Here we show that, rather than the generally accepted 6-bp sequence, PPARα actually recognized a 12-bp DNA sequence, of which the preferred binding sequence was WAWVTRGGBBAH. Additionally, the optimized RXRα hexad binding sequence was RGKTYA. Thus, the optimal PPARα/RXRα heterodimer binding sequence was WAWVTRGGBBAHRGKTYA. The single nucleotide substitution, which reduces binding of RXRα to DNA, attenuated PPARα-induced transcriptional activation, but this is not always true for PPARα. Using the definition of the PPRE sequence, novel PPREs were successfully identified. Taken altogether, the provided PPRE sequence definition contributes to the understanding of PPARα signaling by identifying PPARα direct target genes with functional PPARα response elements.

Rhabdomyolysis is a rare perioperative complication, however, potentially lead to fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old man was seen in our hospital because of asymptomatic grosshematuria. Computed tomography revealed right renal pelvic cancer, cT3N0M0. Right radical nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and the operation was finished without any trouble. At the post-operative day 1, serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive-care unit (ICU), and serum creatinine and creatine kinase level were decreased. At the post-operative day 1, urine myoglobin level was prominently elevated (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case 2) A 40-years old man was incidentally pointed out of right renal tumor that was seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent, and there was no trouble during the operation. After recovering from anesthesia, the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L after the operation. At the postoperative day 1, serum creatine kinase level was markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml, respectively). We diagnosed it rhabdomyolysis, and he received large amount of fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed.

To clarify the discrepancy in the incidence and severity of surgical site infections (SSI) for radical cystectomy between reports based on the CDC guideline and those using the Clavien-Dindo classification we evaluated 449 consecutive patients who underwent radical cystectomy for bladder cancer between 1990 and 2012. Of the 115 (25.6%) patients with SSI defined by the CDC guideline, 89 could be analyzed. We compared the SSI rates and severity defined by the CDC guideline and Clavien-Dindo classifications. There were 58 patients with superficial SSI, 16 with deep SSI, and 15 with organ/space SSI according to the CDC guideline. All patients with organ/space SSI were judged as "not having SSI" by the Clavien-Dindo classification. They were classified as having "intestinal prolapse", "intestinal fistula", "abdominal abscess" and "pelvic abscess." There was a significant association between the treatment duration and depth of SSI based on the CDC guideline by Spearman's rank-correlation coefficient (p < 0.001, r = 0.614) and with the grade of complications (p < 0.001, r = 0.632) in the Clavien-Dindo classification. Multivariate analysis showed that patients with grade III SSI in the Clavien-Dindo classification needed a significantly longer treatment duration. It is necessary to be aware that a discrepancy can occur automatically due to the different natures of the definitions. Using the CDC guideline, we can effectively estimate the future treatment period when SSI occurs. With the Clavien-Dindo classification, grade III SSI requires a longer treatment duration.