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A Belousov–Zhabotinsky (BZ) gel is a unique biomimetic system that undergoes autonomous volume oscillations induced by the redox oscillation of the BZ reaction. In a previous study, researchers reported that the oscillations of two BZ gels coupled by compression were synchronized by a mechanical interaction. They mathematically explained the synchronization behavior using a phase oscillator model. As a different approach to the previous study, a physicochemical investigation of the phenomenon will lead to a better understanding of the functional biological rhythms essential for life. In this study, we construct a simple phenomenological model to understand the synchronization of BZ gels. The model consists of two parts. One is the dynamics of the chemical reactions in the BZ gels. We use a phenomenological model based on the Oregonator for the BZ reaction. The other is the dynamics of the mechanical deformation of the BZ gel. Using approximations, we extract the parameters essential for the synchronization of a mechanical interaction. Thus, we can derive a novel equation for the deformation dynamics of mechanically coupled BZ gels. By combining these two parts, we perform numerical calculations. This allows us to find that the synchronization of the two BZ gels is less likely to occur under stronger compression. We explain this trend through one physicochemical parameter in our model: the volume fraction of the BZ gel in the reduced state. [ABSTRACT FROM AUTHOR]

Purpose: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC.Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed.AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien–Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC.Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC.Methods: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC.Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed.AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien–Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC.Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC.Results: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC.Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed.AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien–Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC.Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC.Conclusion: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC.Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed.AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien–Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC.Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC. [ABSTRACT FROM AUTHOR]

We here introduce three types of self-actuating and nonelectronic machines using chemical reactions and physicochemical transformations. Our strategy is to develop completely artificial and autonomous machines that do not rely on electronic components. We herein demonstrate Belousov-Zhabotinsky gel machines, active droplet machines, and paper machines. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in various malignancies. Lapatinib is a dual tyrosine kinase inhibitor that inhibits both EGFR and HER2. Although a phase III trial failed to show the survival benefits of lapatinib treatment after first-line chemotherapy in patients with EGFR/HER2-positive metastatic urothelial carcinoma, the efficacy of lapatinib for untreated urothelial carcinoma is not well defined. Here, we describe the therapeutic efficacy of lapatinib as a first-line treatment in a canine model of muscle-invasive urothelial carcinoma. In this non-randomized clinical trial, we compared 44 dogs with naturally occurring urothelial carcinoma who received lapatinib and piroxicam, with 42 age-, sex-, and tumor stage-matched dogs that received piroxicam alone. Compared to the dogs treated with piroxicam alone, those administered the lapatinib/piroxicam treatment had a greater reduction in the size of the primary tumor and improved survival. Exploratory analyses showed that HER2 overexpression was associated with response and survival in dogs treated with lapatinib. Our study suggests that lapatinib showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use for untreated advanced urothelial carcinoma in dogs. The use of lapatinib as a first-line treatment may be investigated further in human patients with urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Transvenous embolization (TVE) through the superior ophthalmic vein (SOV) is a useful approach for the treatment of cavernous sinus (CS) dural arteriovenous fistulae (DAVFs). This venous route is usually confirmed by angiography. Herein, we present a case of favorable embolization of the CS DAVF through the angiographically occlusive SOV. A 61-year-old man presented with progressive exophthalmos and hypertonia. The patient was diagnosed with a CS DAVF, and TVE was planned. The first approach through the inferior petrosal sinus was infeasible; therefore, we attempted to approach the fistula through the left facial vein. The microcatheter was easily advanced to the shunt point through the angiographically occlusive SOV. We performed coil embolization, and the CS DAVF was completely obstructed. [ABSTRACT FROM AUTHOR]

Purpose: Skin disorders are the most common stoma-related complications after temporary diverting loop ileostomy with proctectomy. The aim of the present study was to investigate risk factors for skin disorders associated with temporary ileostomy construction. Methods: A total of 185 consecutive patients who underwent curative proctectomy with temporary diverting loop ileostomy for rectal malignancies at a single comprehensive cancer center between 2013 and 2018 were collected and analyzed. Results: The most frequent stoma-related complications were skin disorders (n = 62, 33.5%), followed by mucocutaneous separation (n = 38, 20.5%) and high-output stoma (n = 34, 18.4%). Patients with skin disorders had a higher median body mass index (BMI; 22.4 vs. 21.3 kg/m2, P = 0.002) and lower stoma height (16 vs. 20 mm, P < 0.001) than those without skin disorders. According to a multivariable logistic regression analysis, independent predictors of skin disorders included overweight (median BMI ≥ 25 kg/m2 [odds ratio = 3.6, 95% confidence interval: 1.5–8.6], P = 0.004) and lower stomal height (median stoma height < 20 mm [odds ratio = 3.2, 95% confidence interval: 1.6–6.3], P < 0.001). Conclusion: Overweight and lower stoma height are correlated with the presence of skin disorders. Construction of a well-elevated stoma can reduce skin disorders associated with temporary ileostomy construction. [ABSTRACT FROM AUTHOR]

Recently, we reported highly active transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-β signaling, and PEG10 interfered with the TGF-β and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-β1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-β1-induced motility of SW1353 cells. Individually, TGF-β1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-β signaling and inhibiting cell motility and invasion by interfering with TGF-β and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells. [ABSTRACT FROM AUTHOR]

Transitional cell carcinoma (TCC) accounts for >90% of canine malignant tumours occurring in urinary bladder, and the prognosis is poor. Our previous study, using RNA sequencing, showed that human epidermal growth factor 2 (HER2) was the most activated upstream regulator related to carcinogenesis in canine TCC. The aim of this study was to examine the anti‐tumour effect of lapatinib, a tyrosine kinase inhibitor of HER2, on canine TCC cell lines in vitro and in vivo. Five canine TCC cell lines (TCCUB, Love, Sora, LCTCC, and MCTCC) were used. Western blotting showed that HER2 protein expression was observed in all of the canine TCC cell lines. Lapatinib inhibited phosphorylation of HER2 and cell growth in a dose‐dependent manner. Cell cycle analyses using flow cytometry showed that lapatinib significantly increased the sub‐G1 and G0/G1 phase fractions and significantly decreased the S and G2/M phase fractions in the cell lines (Sora and TCCUB). For the in vivo experiments, the canine TCC cells (Sora) were subcutaneously injected into nude mice. Six days after inoculation, lapatinib (100 mg/kg) or vehicle was administered daily via intraperitoneal administration for 14 days. Tumour volume was significantly smaller in the lapatinib group compared with the vehicle control group. Histologically, lapatinib significantly increased necrotic areas in the tumour tissues. These findings suggest that lapatinib exerts anti‐tumour effects on canine TCC cells by inhibiting HER2 signalling and inducing cell cycle arrest. [ABSTRACT FROM AUTHOR]

Background: Invasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC.Methods: Total RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks.Results: Differential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property.Conclusions: Our data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC. [ABSTRACT FROM AUTHOR]

This paper evaluates a needle-free injector using electrically induced bubbles. For a minimally invasive injector, the configuration of the bubble reservoir, which is at the tip space of the bubble injector, must be optimized because the invasiveness depends on the breakdown distance of the electrically induced bubble. [2017–0121] [ABSTRACT FROM PUBLISHER]

In humans, plasma amino acids (AAs) levels are used as dynamic nutritional markers. Moreover, some AAs are associated with chronic inflammation. In this study, we analyzed plasma AA profiles in cats with chronic gastrointestinal (GI) diseases. Eight healthy controls (HCs) and 12 client-owned cats with chronic GI diseases including chronic enteritis (n = 8) and neoplasms (n = 4) were recruited. Plasma albumin, total protein, and 22 AAs (11 essential and 11 non-essential AAs) levels were estimated. There was no significant difference in plasma albumin and total protein concentrations between the cats with chronic GI diseases and HCs. The plasma concentrations of 7 essential AAs (arginine, histidine, lysine, methionine, phenylalanine, taurine, and tryptophan) and 7 non-essential AAs (asparagine, aspartic acid, glutamic acid, glycine, hydroxyproline, proline, and serine) were significantly decreased in the cats with chronic GI diseases ( P < 0.05). Moreover, plasma histidine and tryptophan levels were inversely correlated with severity of symptoms (histidine: r s = −0.7781, P < 0.005; tryptophan: r s = −0.6040, P < 0.05). To examine the contribution of altered AAs levels in the inflammatory response, feline macrophages were stimulated by lipopolysaccharides (LPS) with or without histidine, and the expression of interleukin-8 (IL-8) mRNA was quantified. The expression of IL-8 mRNA was significantly increased in the LPS-stimulated feline macrophages ( P < 0.05). Histidine almost suppressed the LPS-induced IL-8 expression in the feline macrophages ( P < 0.05). Our findings suggest that plasma AAs levels are more sensitive nutritional markers than albumin and total protein levels in cats with chronic GI diseases. There is a possibility that the decrease of histidine levels in cats with GI diseases is associated with chronic inflammation. [ABSTRACT FROM AUTHOR]

Although tumor-infiltrating lymphocytes (TILs) play a key role in anti-tumor immunity, their involvement in canine transitional cell carcinoma (TCC) is not well-documented. The objective of this study was to investigate the association between TIL number and prognosis in dogs with urinary bladder TCC. Immunohistochemical analysis of CD3 and granzyme B was performed using canine TCC ( n = 32) and normal bladder ( n = 10) tissues. The numbers of CD3 + and granzyme B + cells located in peritumoral stroma of canine TCC were significantly higher than those in normal controls. In TCC cases, the number of CD3 + TILs was not significantly related to prognosis, whereas the abundant granzyme B + TILs were associated with favorable outcome. Since granzyme B + TILs were not associated with the tumor stage, the presence of granzyme B + TILs may be an independent prognostic factor. These results suggest that granzyme B + TILs play a role in anti-tumor immunity and inhibit tumor progression in canine TCC. [ABSTRACT FROM AUTHOR]

Canine idiopathic polyarthritis (IPA) is characterized by increased numbers of polymorphonuclear leukocytes (PMNs) in the synovial fluid (SF). In humans, CC chemokine ligand 2 (CCL2) and CXC chemokine ligand 8 (CXCL8) recruit monocytes and neutrophils, respectively, and are involved in various inflammatory disorders. The aim of this study was to assess the roles of these chemokines in driving PMNs infiltration into the joints of dogs with IPA. SF samples were collected from dogs with IPA (n = 19) and healthy controls (n = 8), and the concentrations of SF CCL2 and CXCL8 were determined by ELISA. Dogs with IPA had significantly higher concentrations of CCL2 (3316 ± 2452 pg/ml, mean ± SD) and CXCL8 (3668 ± 3879 pg/ml) compared with the healthy controls (235 ± 45 pg/ml and <15.6 pg/ml, respectively). Then, an in vitro chemotaxis assay was performed using a modified Boyden chamber (pore size: 3 μm). SF from IPA dogs had a chemoattractant activity for PMNs that purified from the peripheral blood of a healthy dog. We subsequently found that combination treatment with MK-0812 (an antagonist of CCL2 receptor) and repertaxin (an antagonist of CXCL8 receptors) significantly inhibited the migration of PMNs to SF from IPA dogs. Thus, expression of the CCL2 receptor (chemokine (CC motif) receptor 2 (CCR2)) was examined using polymerase chain reaction and immunocytochemistry. Canine peripheral blood PMNs exhibited significantly higher CCR2 mRNA expression levels than those in monocytes. In addition, we observed strong CCR2 expression on PMNs obtained from healthy controls and IPA dogs, although mononuclear cells did not express CCR2. Taken together, the data suggest that CCL2 acts as a canine PMNs chemotactic factor as well as CXCL8 and both CCL2 and CXCL8 facilitate the infiltration of PMNs into the joints of dogs with IPA. [ABSTRACT FROM AUTHOR]

Age-Related Changes in the Left Outflow Tract Introduction Outflow tract ventricular arrhythmias (OT VAs) are common and catheter ablation is an effective treatment option. We sought to investigate the relationship between age-related anatomic aortic root changes and QRS morphology during left ventricular outflow tract (LVOT) pace-mapping using cardiac magnetic resonance (CMR) imaging. Methods and Results Fifty-one patients undergoing CMR imaging were divided into 3 groups based on age (<40, 40-60, >60 years). We measured the angle of the aortic root, the aorta to ventricular septal angle, the distance between the right coronary cusp (RCC) and left coronary cusp (LCC), and the distance between the ascending and descending aorta. Additionally, we evaluated the QRS morphologies obtained during pace-mapping from the LVOT. In older patients, LCC was more superior to the RCC (P < 0.01). Age was positively correlated with the aortic root angle (r2 = 0.481, P < 0.01) as well as the distances between the ascending and descending aorta at a level below the arch (r2 = 0.569, P < 0.01). In older patients, LVOT pace-mapping (performed in 16 patients) demonstrated higher maximal R-wave amplitude, and was greater when pacing from the LCC versus the RCC in lead III (1.8 ± 0.7 vs. 1.0 ± 0.5 mV, P = 0.02). Conclusion The anatomy of the aortic root changes with age, and age-related aortic root changes may affect the QRS morphology during pace-mapping. Understanding the potential anatomic changes that accompany aging is important to maximize the efficacy of catheter ablation of OT VAs. [ABSTRACT FROM AUTHOR]

In Vitro Evaluation of Ice-Cold Saline Irrigation Introduction Irrigated radiofrequency (RF) catheters allow tissue-electrode interface cooling, decreasing thrombus risk while enabling higher RF power delivery. The impact of irrigation with ice-cold saline (ICS) instead of conventional ambient-temperature saline (ATS) on lesion formation is unknown. Methods and Results We performed 120 RF ablations in vitro on porcine left ventricles, using ICS (<5 °C) or ATS (21 °C) irrigation. For ICS irrigation, the irrigation circuit was cooled externally to maintain delivery of cooled saline at the catheter's tip. We applied 20 g of contact force, and delivered 20 W (irrigation 8 or 17 mL/min) or 30 W (irrigation 17 or 30 mL/min) RF power. Temperatures at tissue-electrode interface and 3-mm depth were assessed by fluoroptic probes. Lesion dimensions were assessed. ICS irrigation cooled the tissue-electrode interface better than ATS (53.9 ± 9.6 °C vs. 63 ± 11.4 °C, P < 0.001). Temperatures at 3-mm depth were similar at 30 W using ICS and ATS (104.2 ± 9.3 °C vs. 105.8 ± 7.3 °C, P = 0.5), but were cooler at 20 W using ICS (71.3 ± 11.6 °C vs. 100.2 ± 11.9 °C, P < 0.001). This translated into smaller lesions at 20 W with ICS versus ATS. At 30 W with 17 mL/min flow rate, lesions had the same depth with ICS and ATS (4.9 ± 0.8 mm vs. 5.4 ± 0.7 mm, P = 0.13) but were narrower with ICS (7.7 ± 0.8 mm vs. 9.3 ± 1.2 mm, P = 0.001). At 30 mL/min, lesions had the same dimensions. Steam pop rate was similar using ICS or ATS irrigation. Conclusion ICS irrigation more effectively cools tissue-electrode interface than ATS. This may improve RF safety by potentially decreasing thrombus formation, thus facilitating safe ablation at a low saline volume load. However at lower RF power, ICS reduced lesion size compared to ATS. [ABSTRACT FROM AUTHOR]

Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further investigations into the effects on diseased dogs are needed. [ABSTRACT FROM AUTHOR]

Abstract: Although decreased intestinal IgA expression has been reported in dogs with inflammatory bowel disease (IBD), the mechanism underlying this decrease is unknown. Transmembrane activator and calcium-modulating cyclophilin–ligand interactor (TACI) and B cell-activating factor of the TNF family (BAFF) receptor (BAFF-R) are key receptors for T cell-independent IgA class switching by the binding of IgA-inducing cytokine a proliferation-inducing ligand (APRIL) and BAFF. Here we show decreased TACI and BAFF-R mRNA expression and hypermethylation of their corresponding genes TNFRSF13B and TNFRSF13C, respectively in the duodenal mucosa of dogs with IBD. To examine whether DNA methylation of the TNFRSF13B and TNFRSF13C influences the mRNA expression of TACI and BAFF-R, respectively, we first analyzed methylation and mRNA expression levels in vitro using 2 canine B lymphoid cell lines, GL-1 and CLBL-1. Methylation profiles in the cells were examined by bisulfite sequencing and methylation-specific PCR (MSP) with primer pairs specific to methylated or unmethylated sequences. These methylation analyses revealed hypermethylation of the CpG islands of both TNFRSF13B and TNFRSF13C in GL-1, but not in CLBL-1 cells. The mRNA expression levels of TACI and BAFF-R were significantly lower in GL-1 than in CLBL-1 cells. Treatment with 5-aza-2′-deoxycytidine significantly increased TACI and BAFF-R mRNA expression in GL-1 cells through demethylation of TNFRSF13B and TNFRSF13C, respectively. These results suggest that the mRNA expression of TACI and BAFF-R is regulated through methylation of their genes in canine B cells. Quantitative real-time MSP showed significant hypermethylation of the CpG islands of TNFRSF13B and TNFRSF13C in the duodenal mucosa of dogs with IBD. Furthermore, duodenal mRNA expression levels of TACI and BAFF-R were significantly lower in dogs with IBD than in healthy controls. The mRNA expression levels of TACI positively correlated with intestinal IgA expression, whereas the methylation level of its gene (TNFRSF13B) negatively correlated with IgA expression. The present results suggest the role of TACI in the regulation of mucosal IgA expression through epigenetic modifications. [Copyright &y& Elsevier]

Background: Atrial anti-tachycardia pacing (A-ATP) of the right atrium (RA) has been shown to decrease the burden of atrial fibrillation (AF) in patients with dual-chamber pacemakers. The aim of this study is to identify the novel predictors of effective A-ATP for terminating AF in patients with AF undergoing catheter ablation. Methods: This study included 41 consecutive patients undergoing a first ablation procedure for paroxysmal (PAF: n = 21) or persistent (PEF: n = 20) AF. We prospectively evaluated predictors of AF termination after A-ATP. The coefficient of variation (CoV = SD/mean × 100) of the dominant frequencies (DFs) was calculated to evaluate the variability in atrial activation. Results: AF was terminated by A-ATP in 29% of PAF and 5% of PEF patients. In these patients, simultaneous high-rate pacing from the RA and the coronary sinus (CS) terminated AF in 71% of patients, in whom the mean AF cycle length (CL) before A-ATP was longer (214 ± 23 vs. 177 ± 35 ms, p = 0.02) and became slower after A-ATP (234 ± 37 vs. 176 ± 32 ms, p < 0.01), compared to unsuccessful patients. The CoV of the DFs before A-ATP were lower in both RA (6.2 ± 2.0 vs. 15.3 ± 7.9, p = 0.02) and CS (11.0 ± 7.9 vs. 24.3 ± 9.3, p < 0.01) in successful patients. Conclusions: Simultaneous biatrial A-ATP from the RA and CS could terminate AF in patients with PAF. The predictors for successful termination include longer AF CL and higher AF stability. [ABSTRACT FROM AUTHOR]

A novel gel actuator exhibits a peristaltic motion is designed. We proposed a new approach of coupling an acid-autocatalytic reaction and a pH-responsive gel in order to cause contraction waves. The poly(AAm-co-AAc) microphase-separated tubular gel was synthesized, which can be inflowed reaction solution to its hollow. We focused on its kinetics and evaluated the characteristics of the microphase-separated gels. And we also demonstrated that the propagation of the contraction region occurs in the tubular gel. Our final goal is to develop a biomimetic chemical robot, which realizes a peristaltic locomotion by forming contraction waves like a snail. [ABSTRACT FROM AUTHOR]

Abstract: Although the molecular basis of the allergenicity remains to be fully elucidated, the ability of allergens to elicit allergic responses is at least partly attributed to their proteolytic activity. Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is activated by site-specific proteolysis by serine proteases and is known to mediate inflammatory processes in various tissues. In this study, we investigated the effects of trypsin, a major serine protease, and a human PAR-2 agonist peptide (SLIGKV-NH2) on proinflammatory cytokine and chemokine gene expression in the canine keratinocyte cell line CPEK. The expression of PAR-2 mRNA and protein in CPEK cells was detected by RT-PCR and Western blotting, respectively. The localization of PAR-2 in CPEK was examined by immunofluorescence. The mRNA expression levels of proinflammatory cytokines and chemokines were quantified by real-time RT-PCR. The free intracellular Ca2+ concentration was measured using the Ca2+-sensitive fluorescent dye. CPEK cells constitutively expressed PAR-2 mRNA and protein. Stimulation of CPEK cells with trypsin induced significant upregulation of the mRNA expression levels of tumor necrosis factor alpha (TNF-α, P <0.05), granulocyte-macrophage colony-stimulating factor (GM-CSF, P <0.01), thymus and activation regulated chemokine (TARC/CCL17, P <0.01), and interleukin 8 (IL-8/CXCL8, P <0.01). Similarly, the PAR-2 agonist peptide increased the mRNA expression levels of TNF-α (P <0.05), GM-CSF (P <0.05), TARC/CCL17 (P <0.05), and IL-8/CXCL8 (P <0.05) in CPEK cells. Both trypsin and the PAR-2 agonist peptide increased the intracellular Ca2+ concentration and PAR-2 internalization. These results suggest that PAR-2 activation can augment inflammatory cytokine and chemokine expression in canine keratinocytes, and it may initiate allergic inflammation through the proteolytic activity of allergens in canine atopic dermatitis. [Copyright &y& Elsevier]

In this study, The volume oscillation of the microphase-separated, self-oscillating gel above the volume phase transition temperature is discussed. The self-oscillating gel is composed of N-isopropylacrylamide (NIPAAm) with a metal catalyst for the Belousov-Zhabotinsky (BZ) reaction, which is known as the oscillating reaction. The influence of temperature on the period and the self-oscillating behavior is clarified. The volume change of the gel is explained by a change of the Flory-Huggins interaction parameter, χ, which is induced by the hydration and dehydration of the polymer chain due to a valance change of the metal catalyst (Ru(bpy)32+ ↔ Ru(bpy)33+) below the volume phase-transition temperature. In contrast, the volume change of the gel is explained by a change of the Donnan osmotic pressure. [ABSTRACT FROM AUTHOR]

Many authors have studied variation in the maxillary artery but there have been inconsistencies between reported observations. The present research aimed to examine the courses and branching patterns of the trunk and branches of the maxillary artery in a large sample of Japanese adult cadavers. The course of the maxillary artery should be reclassified into seven groups as a clear relationship was found between the origin of the middle meningeal artery and the course of the maxillary artery. This indicates that conventional theory about the formation of the maxillary artery, which was considered to be a direct derivative of the stapedial artery, might be inaccurate. Many variations in the origin of the inferior alveolar artery were found. Notably, the inferior alveolar artery origin from the external carotid artery and a double origin of the inferior alveolar artery was also observed. Thus, the maxillary artery might be derived from a combination of both the external carotid and stapedial arteries. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-1β is a key mediator of the inflammatory response. IL-1 receptor antagonist (IL-1Ra) regulates inflammation by functioning as an endogenous inhibitor of IL-1β. A disruption of the balance between IL-1β and IL-1Ra has been identified in human inflammatory bowel disease (IBD). The objective of this study was to determine whether there is an intestinal imbalance of IL-1β and IL-1 Ra in canine IBD by comparing expression of IL-1β and IL-1Ra mRNA by real-time RT-PCR and expression of IL-1β and IL- lRa protein by ELISA in 21 dogs with IBD, 15 dogs with intestinal lymphoma ('inflammatory' controls) and 20 healthy Beagles ('healthy' controls). A significant decrease in the intestinal IL-1Ra:IL-1β ratio of mRNA and protein was observed in IBD cases when compared with healthy control dogs. In contrast, a decrease in IL-1Ra:IL-1β ratio was not observed in dogs with intestinal lymphoma. The IL-1Ra:IL-1β protein ratio was negatively correlated with clinical severity in dogs with IBD. An intestinal imbalance between IL-1β and IL-1Ra production may play a role in the pathogenesis of canine IBD. [ABSTRACT FROM AUTHOR]

Hypertrophic maturation of chondrocytes is a crucial step in endochondral ossification, whereas abnormally accelerated differentiation of hypertrophic chondrocytes in articular cartilage is linked to pathogenesis of osteoarthritis. This cellular process is promoted or inhibited by bone morphogenetic protein (BMP) or transforming growth factor-β (TGF-β) signaling, respectively, suggesting that these signaling pathways cross-talk during chondrocyte maturation. Here, we demonstrated that expression of Tgfb1 was increased, followed by phosphorylation of Smad2, during BMP-2-induced hypertrophic maturation of ATDC5 chondrocytes. Application of a TGF-β type I receptor inhibitor compound, SB431542, increased the expression of Id1, without affecting the phosphorylation status of Smad1/5/8, indicating that the activated endogenous TGF-β pathway inhibited BMP signaling downstream of the Smad activation step. We searched for TGF-β-inducible effectors that are able to inhibit BMP signaling in ATDC5 cells and identified SnoN. Overexpression of SnoN suppressed the activity of a BMPresponsive luciferase reporter in COS-7 cells as well as expression of Id1 in ATDC5 cells and, subsequently, the expression of Col10a1, a hallmark of hypertrophic chondrocyte maturation. siRNA-mediated loss of SnoN showed opposite effects in BMP-treated ATDC5 cells. In adult mice, we found the highest level of SnoN expression in articular cartilage. Importantly, SnoN was expressed, in combination with phosphorylated Smad2/3, in prehypertrophic chondrocytes in the growth plate of mouse embryo bones and in chondrocytes around the ectopically existing hypertrophic chondrocytes of human osteoarthritis cartilage. Our results indicate that SnoN mediates a negative feedback mechanism evoked by TGF-β to inhibit BMP signaling and, subsequently, hypertrophic maturation of chondrocytes. [ABSTRACT FROM AUTHOR]

Abstract: The interaction between fractalkine/CX3CL1 and its receptor CX3CR1 has been reported to play an important role in various human inflammatory diseases, including inflammatory bowel disease (IBD) mediated by lymphocyte chemoattraction. The objective of this study was to investigate the role of fractalkine and CX3CR1 in lymphocyte migration in canine IBD. IBD was diagnosed in 34 dogs, and 19 healthy beagles were used as normal controls. We quantified intestinal mRNA and protein expression of fractalkine and CX3CR1 by real-time RT-PCR and ELISA, respectively, and examined the localization of fractalkine in canine intestine by immunohistochemistry. The expression of CX3CR1 and surface antigens on peripheral blood mononuclear cells (PBMCs) and intraepithelial lymphocytes (IELs) was analyzed by flow cytometry. Intestinal fractalkine and CX3CR1 mRNA was significantly up-regulated in IBD dogs compared with the healthy control dogs. In addition, fractalkine expression on intestinal epithelial cells was significantly increased in the intestinal mucosa of IBD dogs compared with the healthy dogs. CX3CR1+ PBMCs were significantly elevated in IBD dogs and positively correlated with the histopathological severity of IELs infiltration. These CX3CR1+ PBMCs predominantly expressed markers for cytotoxic T cells. Almost all IELs expressed CD3, and the majority of cells expressed CD8 rather than CD4, which was analogous to the CX3CR1+ PBMCs. These results suggest that the fractalkine-CX3CR1 interaction may contribute to the pathogenesis of canine IBD through migration of IELs. [Copyright &y& Elsevier]

The circadian rhythm is a fundamental physiological function for a wide range of organisms. The molecular machinery for generating rhythms has been elucidated over the last few decades. Nevertheless, the mechanism for temperature compensation of the oscillation period, which is a prominent property of the circadian rhythm, is still controversial. In this study, we propose a new mechanism through a chemically synthetic approach (i.e., we realized temperature compensation by the Belousov–Zhabotinsky (BZ) gels). The BZ gels are prepared by embedding a metal catalyst of the BZ reaction into the gel polymer. We made the body of BZ gels using a temperature-sensitive polymer gel, which enabled temperature compensation of the oscillation by using temperature dependence of volume. Moreover, we constructed a simple mathematical model for the BZ oscillation in temperature-sensitive gels. The model can reproduce temperature compensation of BZ gels, even though all reactions are temperature sensitive according to the Arrhenius rule. Our finding hints that a soft body coupling may be underlying temperature-compensated biological functions, including circadian rhythms. [ABSTRACT FROM AUTHOR]

Abstract: The chemokine receptor CCR9, which interacts with the thymus-expressed chemokine TECK/CCL25, contributes to the localization of lymphocytes to the small intestine, and is implicated in the development of human inflammatory bowel disease (IBD); however, their role in canine IBD is unknown. The objective of this study was to isolate cDNA encoding CCR9 and to investigate CCR9 expression in normal canine tissues and lymphoid cell lines. The complete open reading frame contained 1104bp, encoding 367 amino acids, with 85% and 81% identity to human and mouse homologs, respectively. CCR9 mRNA was detected in all tissues investigated with the highest expression level in the small intestine. CCR9 mRNA was also expressed in GL-1, a canine B cell leukemia cell line, but not in CLBL-1, a canine B cell lymphoma cell line. Immunoblot and flow cytometry analyses of these cell lines using an anti-human CCR9 monoclonal antibody revealed that CCR9 protein expression was detected only in GL-1, indicating the cross-reactivity of the antibody. Using the antibody, flow cytometry showed that the proportions of CCR9+ cells were small (mean, 4.88%; SD, 2.15%) in the normal canine PBMCs. This study will be useful in understanding canine intestinal immunity and the immunopathogenesis of canine IBD. [Copyright &y& Elsevier]

Abstract: Fractalkine, also known as CX3CL1, is a unique chemokine that mediates inflammatory responses and is involved in the pathogenesis of several inflammatory disorders, including inflammatory bowel disease (IBD) in humans. In this study, we isolated cDNAs encoding canine fractalkine and its receptor CX3CR1, and assessed the biological activity of these molecules. The deduced amino acid sequence of the canine fractalkine cDNA showed 66% and 57% identity to human and mouse homologs, respectively. The N-terminal chemokine domain of the canine fractalkine showed 68% and 65% identity to human and mouse counterparts, respectively. The canine CX3CR1 amino acid sequence showed close homology to its human (83% identity) and mouse (81% identity) counterparts. Fractalkine and CX3CR1 mRNA were detected in all tissues in this study. Relatively higher expression levels of fractalkine mRNA were observed in the brain, medulla spinalis, small intestine, and mesenteric lymph nodes (MLNs), whereas higher expression levels of CX3CR1 mRNA were observed in the medulla spinalis, brain, liver, small intestine, and MLNs. The cross-reactivities of anti-human fractalkine antibody and anti-rat CX3CR1 antibody to canine proteins were confirmed using recombinant canine fractalkine and a cell line overexpressing canine CX3CR1, respectively. A transwell chemotaxis assay showed that the recombinant canine fractalkine induced migration in canine lymphoid cells expressing CX3CR1. The present study will be useful in understanding the canine immune system and the immunopathogenesis of canine inflammatory diseases. [Copyright &y& Elsevier]

Few studies have explored the topographic anatomy of the esophagus, posterior wall of the left atrium (LA), or fat pads using multidetector computed tomography (MDCT) to prevent the risk of esophageal injury during atrial fibrillation (AF) ablation. MDCT was performed in 110 consecutive patients with paroxysmal or persistent AF before the ablation procedure to understand the anatomic relationship of the esophagus. Two major types of esophagus routes were demonstrated. Leftward (type A) and rightward (type B) routes were found in 90 and 10% of the patients, respectively. A type A route had a larger mean size of the LA than type B. The fat pad was identifiable at the level of the inferior pulmonary vein in 91% of the patients without any predominance of either type. The thickness of the fat pad was thinner in the patients with a dilated LA (>42 mm) than in those with a normal LA size (≤42 mm) ( p = 0.01). The results demonstrated that the majority of cases had a leftward route of the esophagus. There was a close association between the LA dilatation and fat pad thinning. With a dilated LA, the esophagus may become easily susceptible to direct thermal injury during AF ablation. Visualization of the anatomic relationship may contribute to the prevention of the potential risk of an esophageal injury. [ABSTRACT FROM AUTHOR]

Abstract: Although chemokines and their receptors play an integral role in the regulation of the immune response, there is very little information about their involvement in canine inflammatory bowel disease (IBD). The objective of this study was to evaluate the mRNA expression of 9 selected chemokines and 6 chemokine receptors by real-time reverse transcription PCR in the duodenal mucosa from 21 dogs with IBD and 25 control dogs. The transcription levels of monocyte chemotactic protein-1 (MCP-1)/CCL2, macrophage inflammatory protein-3 alpha (MIP-3α)/CCL20, thymus-expressed chemokine (TECK)/CCL25, mucosae-associated epithelial chemokine (MEC)/CCL28 and IL-8/CXCL8 mRNA in IBD dogs were significantly higher than the corresponding levels in control dogs, but there was no significant difference in the mRNA levels of the chemokine receptors between the 2 groups. In addition, the CCL2 and CXCL8 mRNA levels were significantly higher in the high clinical severity score group than in the low clinical severity score group. However, there was no correlation between chemokine or chemokine receptor mRNA expressions and histopathological severity score. The present results suggest that several chemokines may play important roles in the pathogenesis of canine IBD. [Copyright &y& Elsevier]

Abstract: A noncascading terahertz (THz) wave parametric oscillator synchronously pumped by a mode-locked picosecond Ti:sapphire laser whose average power was less than 1W was demonstrated with a noncollinear phase-matching MgO:LiNbO3 crystal in an external enhancement cavity doubly resonant for both pump (780nm) and signal (781–784nm) waves. In the external cavity, in which the pump wave enhanced so as to reduce the pumping threshold of parametric processes, the signal wave could also resonate and thus be enhanced simultaneously, resulting in a THz wave output at approximately 0.9THz as the idler wave. The novel dual enhancement of pump and signal waves reduced the threshold pumping intensity to approximately 50MW/cm2, which was much lower than that of a conventional externally pumped THz wave parametric oscillator with a crystal. [Copyright &y& Elsevier]

Few studies have explored the utility of local electrogram-guided extensive encircling pulmonary vein isolation (EEPVI) by analyzing the pulmonary vein (PV) anatomy and occurrence of stenosis using multidetector computed tomography (MDCT). One hundred seventy-six paroxysmal atrial fibrillation (AF) patients underwent EEPVI with a double lasso technique. MDCT was performed in all patients before and at 3, 6 and 12 months after the ablation procedures to screen for PV stenosis. PV stenosis was defined as a >30% reduction in its diameter. A total of 700 PVs were analyzed. PV stenosis was observed in 15 of 700 PVs (2.1%). All stenoses were mild (mean 34.5 ± 3.3%). They were all asymptomatic, and none required treatment. After 12 months of follow-up, the PV narrowing regressed significantly compared with that at 3 months in the patients with PV stenosis (34.5 ± 3 to 30.4 ± 5%, P < 0.05). The remaining PVs exhibited a stable anatomy, and there was no significant progression of the PV narrowing. The results of this study demonstrated that detectable PV stenosis occurred in 2.1% of the PVs, and all stenoses were mild. Moreover, a significant regression of the PV narrowing was observed after 12-months of follow-up. This indicates that the local electrocardiogram-guided EEPVI was relatively safe regarding severe PV stenosis. [ABSTRACT FROM AUTHOR]

In this paper, we introduce autonomous gel actuators driven by chemical energy. The polymer gels prepared here have cyclic chemical reaction networks. With a cyclic reaction, the polymer gels generate periodical motion. The periodic motion of the gel is produced by the chemical energy of the oscillatory Belouzov-Zhabotinsky (BZ) reaction. We have succeeded in making synthetic polymer gel move autonomously like a living organism. This experimental fact represents the great possibility of the chemical robot. [ABSTRACT FROM AUTHOR]

Background: Telmisartan has been shown to exert an equivalent action as ramipril on the prevention of cardiovascular events, but the dose-dependent actions of telmisartan on the prevention of events remain unknown. Objective: We investigated the dose-dependent effects of telmisartan on the prevention of AF in patients associated with risk factors. Methods: One hundred hypertensive patients were randomized to take 40 mg (low-dose group: n=57) or 80 mg (high-dose group: n=43) of telmisartan for 24 months. The primary endpoints were defined as a new development and/or recurrence of atrial fibrillation (AF). Results: The mean values of the blood pressure in both groups decreased significantly and to similar degrees after 24 months, in the low-dose (p < 0.01) and high-dose (p < 0.01) groups. At the end of the follow-up, the incidence of AF was lower in the high-dose group than in the low-dose group (p < 0.05). Moreover, the proportion of AF recurrences in the patients with a past history of paroxysmal AF was lower in the high-dose group than in the low-dose group (p < 0.05). Further, using a logistic regression model, there were no risk factors associated with the incidence of AF. Conclusion: The results indicated that telmisartan in low doses was as effective in controlling the blood pressure as in high doses, but high doses of telmisartan had beneficial effects on preventing the recurrence of AF in hypertensive patients. [ABSTRACT FROM AUTHOR]

If we could realize an autonomous polymer system driven under biological conditions by a tailor-made molecular design, human beings could create unprecedented biomimetic functions and materials such as heartbeats, autonomous peristaltic pumps, etc. In order to achieve this objective, we have investigated the molecular design of such a polymer system. As a result, we were the first to demonstrate a self-oscillating polymer system driven in a solution where only malonic acid existed, which could convert the chemical energy of the Belousov-Zhabotinsky (BZ) reaction into a change in the conformation of the polymer chain. To cause the self-oscillation in solution, we have attempted to construct a built-in system where the required BZ system substrates other than the organic acid are incorporated into the polymer itself. That is, the novel polymer chain incorporated the metal catalyst of the BZ reaction, a pH-control site and an oxidant supply site at the same time. As a result of introducing the pH control and oxidant supply sites into the conventional-type self-oscillating polymer chain, the novel polymer chain caused aggregation-disaggregation self-oscillations in the solution. We clarified that the period of the self-oscillation of the novel self-oscillating polymer chain was proportional to the concentration of the malonic acid. Therefore, the concentration of the malonic acid can be determined by measuring the period of the novel self-oscillating polymer solution. In this review, we introduce the detailed molecular design of the novel self-oscillating polymer chain and its self-oscillating behavior. Moreover, we report an autonomous self-oscillating polymer gel actuator that causes a bending-stretching motion under the constant conditions. [ABSTRACT FROM AUTHOR]

Many kinds of stimuli-responsive polymer and gels have been developed and applied to biomimetic actuators or artificial muscles. Electroactive polymers that change shape when stimulated electrically seem to be particularly promising. In all cases, however, the mechanical motion is driven by external stimuli, for example, reversing the direction of electric field. On the other hand, many living organisms can generate an autonomous motion without external driving stimuli like self-beating of heart muscles. Here we show a novel biomimetic gel actuator that can walk spontaneously with a wormlike motion without switching of external stimuli. The self-oscillating motion is produced by dissipating chemical energy of oscillating reaction. Although the gel is completely composed of synthetic polymer, it shows autonomous motion as if it were alive. [ABSTRACT FROM AUTHOR]

Abstract: House dust mite (HDM) allergens are the most common allergens involved in the induction of IgE-mediated hypersensitivity. Recently, epicutaneous sensitization with HDM allergens has been emphasized in the development of atopic dermatitis (AD); however, direct stimulation of canine keratinocytes by mite allergens has not been well investigated. In the present study, we investigated the effects of Der f 1, a major allergen of Dermatophagoides farinae, on cytokine and chemokine gene expression in a canine keratinocyte cell line, CPEK. CPEK constitutively expressed mRNA for TNF-α, IL-12p35, IL-18, GM-CSF, TGF-β, IL-8/CXCL8, TARC/CCL17, CTACK/CCL27 and MEC/CCL28. Of all the cytokines and chemokines investigated in CPEK, transcription levels of GM-CSF, IL-8/CXCL8 and TNF-α mRNA were significantly enhanced by stimulation with Der f 1. The present results suggest that Der f 1 can directly augment inflammatory cytokine and chemokine production from keratinocytes, and may initiate allergic inflammation independently of Type-I hypersensitivity. [Copyright &y& Elsevier]

Abstract: Single-frequency coherent light from a Ti:sapphire laser at 778nm was frequency-doubled efficiently in a high-finesse resonant cavity containing a BiBO crystal to generate an output at 389nm, which was the resonant wavelength of 23S1 →33P2 of 3He. The 389nm cw coherent light was obtained with the conversion efficiency of 56%, even at the relatively low input power of about 700mW. The laser frequency was also locked to the doubling-cavity resonance by the Hänsch–Couillaud technique. [Copyright &y& Elsevier]

In this paper, we introduce self-oscillating gel actuators for chemical robotics. The polymer gels prepared here have cyclic reaction networks like in a metabolic process itself. With a cyclic reaction, the polymer gel swells–shrinks autonomously. The periodic self-oscillating motion of the gel is produced by the dissipating chemical energy of the oscillatory Belouzov–Zhabotinsky reaction. We have succeeded in making the synthetic polymer gel walk autonomously like a living organism. This experimental fact represents the great possibility of the chemical robot. [ABSTRACT FROM AUTHOR]

Abstract: An efficient 389nm coherent light source, made possible through the single-pass second-harmonic generation of a picosecond Ti:sapphire laser with a periodically poled lithium niobate waveguide, was developed for the metastability exchange optical pumping of hyperpolarized 3He gas, which is applicable to imaging with nuclear magnetic resonance. The second-harmonic light provided such a broad spectrum that some split sub-levels of its metastable state under an applied magnetic field could be pumped efficiently and simultaneously. Optogalvanic spectroscopy using the light source indicated that the spectral width of 3He was much less than 70GHz, which was similar to the spectral width of the light source. [Copyright &y& Elsevier]

Muscle cells are often exposed to bone morphogenetic proteins (BMPs) in pathological muscle and/or bone conditions. Because BMPs function as strong bone inducers as well as myogenesis inhibitors, certain molecules likely prevent muscle cells from converting into pathologic bone; without these molecules, de novo bone would form as observed in myositis ossificans traumatica. When C2C12 myoblasts are exposed to BMPs, they differentiate into osteoblastic cells but cannot mature into bone cells. As the Osterix gene, a transcription factor for osteoblast differentiation, is only transiently induced upon BMP stimulation in C2C12 cells, we hypothesized that unknown transcriptional repressor(s) inhibit Ostertx expression and prevent complete osteoblastic differentiation. Gene microarray analyses were performed to identify putative inhibitors for osteoblastic differentiation, and the paired-like homeodomain transcription factor Pitx2 (also termed Rieg), which plays an important regulatory role in left-right asymmetry, was identified. Pitx2 was induced 2 days after BMP stimulation in C2C12 cells in concert with Osterix down-regulation. Overexpression of Pitx2 repressed Osterix expression and subsequent osteoblastic differentiation, whereas Runx2, the most upstream regulator of osteogenesis, was unaffected. Conversely, the induction of short hairpin RNA for Pitx2 in C2C12 cells enhanced Osterix expression and osteoblastic maturation upon BMP stimulation. Moreover, mouse embryonic fibroblasts containing myoblasts from Pitx2-null embryos showed enhanced Osterix expression upon BMP stimulation. These findings suggest that Pitx2 suppresses osteogenic signals induced by BMPs in myoblasts to prevent their osteoblastic conversion. [ABSTRACT FROM AUTHOR]

Abstract: The inhibitory effects of nucleotides and related substances on rat hepatic UDP-glucuronosyltransferase (UGT) were studied. ATP and NADP+ markedly reduced 4-methylumbelliferone (4-MU) UGT activity only when detergent-treated rat liver microsomes were used as the enzyme source. The IC50 values of adenine, ATP, NAD+ and NADP+ were estimated to be below 20 μM, whereas AMP had no inhibitory effect. From the kinetic behavior observed, these adenine-related compounds were assumed to inhibit UGT activity non-competitively without competing with either 4-MU or UDP-glucuronic acid. Among guanine, cytosine and their related nucleotides, only triphosphate nucleotides (CTP and GTP) exhibited potent UGT inhibition, although the effect of GTP was weak. Estradiol 3- and 17-glucuronidation were also inhibited by the inhibitors of 4-MU UGT. The only exception was that estradiol 17-glucuronidation activity was inhibited by AMP (IC50 =31 μM). In addition, AMP antagonized the inhibitory effects of adenine, ATP, and NADP+ on 4-MU and estradiol 3- glucuronidation activities. These results suggest that (1) a number of cellular nucleotides present within the endoplasmic reticulum regulate UGT function; and (2) these substances bind to a common allosteric site on UGT to reduce catalytic function. [Copyright &y& Elsevier]

Abstract: Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) superfamily, bind to two different serine/threonine kinase receptors, and mediate their signals through Smad-dependent and Smad-independent pathways. Receptor regulated-Smad (R-Smad) proteins specific for the BMP pathways interact with various proteins, including transcription factor Runx, and transmit specific signals in target cells. The recent development of DNA microarray techniques has allowed us to identify many BMP target genes. BMP signaling is modulated by various molecules, including inhibitory Smads (I-Smads). Moreover, recent findings have revealed that BMP pathways interact with other signaling pathways, and such signaling cross-talk plays pivotal roles in growth and differentiation of target cells. [Copyright &y& Elsevier]

Runx proteins regulate various biological processes, including growth and differentiation of hematopoietic cells, lymphocytes, osteoblasts, and gastric epithelial cells. Some of the biological activities of Runx proteins are reminiscent of those of transforming growth factor (TGF)-β superfamily cytokines. Consistent with this notion, receptor-regulated Smads (R-Smads), signal mediators of the TGF-β superfamily cytokines, and Runx proteins have been shown to physically interact with each other. R-Smads activated by TGF-β and Runx proteins cooperatively induce synthesis of IgA in B lymphocytes, and those activated by bone morphogenetic proteins and Runx2 induce osteoblastic differentiation. Moreover, the R-Smad—Runx signaling pathways are regulated by an E3 ubiquitin ligase Smurf1, as well as a signal transducer of interferons, STAT1. Since Runxl and Runx3 are involved in the development of some cancers including acute leukemia and gastric cancer, it will be of interest to examine in detail whether TGF-β-specific R-Smads and Runx proteins coordinately regulate growth and differentiation of hematopoietic cells and gastric epithelial cells. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β), one of the most abundant cytokines in bone matrix, has positive and negative effects on bone formation, although the molecular mechanisms of these effects are not fully understood. Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, induce bone formation in vitro and in vivo. Here, we show that osteoblastic differentiation of mouse C2C12 cells was greatly enhanced by the TGF-β type I receptor kinase inhibitor SB431542. Endogenous TGF-β was found to be highly active, and induced expression of inhibitory Smads during the maturation phase of osteoblastic differentiation induced by BMP-4. SB431542 suppressed endogenous TGF-β signaling and repressed the expression of inhibitory Smads during this period, possibly leading to acceleration of BMP signaling. SB431542 also induced the production of alkaline phosphatase and bone sialoprotein, and matrix mineralization of human mesenchymal stem cells. Thus, signaling cross-talk between BMP and TGF-β pathways plays a crucial role in the regulation of osteoblastic differentiation, and TGF-β inhibitors may be invaluable for the treatment of various bone diseases by accelerating BMP-induced osteogenesis. [ABSTRACT FROM AUTHOR]

Low-temperature methane oxidation over oxide-supported Pd catalysts coated on a metal or ceramic honeycomb was investigated for gas turbine applications. Al2O3 and SnO2 were used as washcoat material, and a Fe–Cr–Al alloy and cordierite were adopted as metal and ceramic honeycombs, respectively. Pd catalysts on the honeycomb were prepared by varying washcoat loading and washcoat calcination temperature. It was found that the catalytic activities of Pd/SnO2 on metal and ceramic honeycombs improved with increasing washcoat loading and precalcination temperature of the washcoat material. Especially, significant enhancement of the catalytic activity appeared for Pd/SnO2/ceramic honeycomb as the washcoat loading increased from 150 to 200 g/l. The catalytic activity of the honeycomb catalysts was examined under high pressure and space velocity. The temperature at which the increase in CH4 conversion became noticeable was shifted to higher temperature compared to the experiments at lower space velocity and ambient pressure. CH4 conversion over the honeycomb catalysts fluctuated as the catalyst bed inlet temperature was raised. Pd/SnO2/ceramic honeycomb exhibited the highest stable activity for low-temperature methane oxidation. [Copyright &y& Elsevier]

The influence of water vapor on the activity for low-temperature methane oxidation over oxide-supported catalysts such as Pd/Al2O3, Pd/SnO2, and Pd/Al2O3-36NiO was studied. It was found that Pd/Al2O3 was deactivated most significantly due to water vapor, and that Pd/Al2O3-36NiO was most insensitive to water vapor. The catalytic activity of Pd/Al2O3 decreased monotonically as water vapor concentration increased, whereas Pd/SnO2 and Pd/Al2O3-36NiO showed almost constant activity under higher water vapor concentrations. The catalytic activity at high steam concentration was in the following order: Pd/SnO2>Pd/Al2O3-36NiO>Pd/Al2O3. Kinetic analysis with methane adsorption as the rate-limiting step was applied to evaluate the water inhibiting effect. Pd/Al2O3 displayed the most negative value of the enthalpy of water adsorption, while Pd/SnO2 and Pd/Al2O3-36NiO exhibited similar water adsorption enthalpy.Deactivation and regeneration of Pd/SnO2 and Pd/Al2O3 catalysts were investigated by cyclic feed of water vapor. Both the catalysts were deactivated rapidly upon switching on water feed, and then they regenerated gradually to the initial activity after the water feed was switched off. [Copyright &y& Elsevier]

We describe a case with three focal atrial tachycardias (ATs) and focal atrial fibrillation (AF) originating from the interatrial septum (IAS) near the atrioventricular node (AVN). Contrast-enhanced computed tomography demonstrated the association of fat deposition within the anterior IAS near the AVN with successful ablation sites of these ATs and AF. This is the first report that the intramural fat deposition in the IAS could be associated with the formation of AT and AF re-entry circuits originating near the AVN. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) is used for pathological diagnosis and obtaining samples for molecular testing, facilitating the initiation of targeted therapies in patients with pancreatic cancer. However, samples obtained via EUS‐TA are often insufficient, requiring more efforts to improve sampling adequacy for molecular testing. Therefore, this study investigated the use of oil blotting paper for formalin fixation of samples obtained via EUS‐TA. Methods: This prospective study enrolled 42 patients who underwent EUS‐TA for pancreatic cancer between September 2020 and February 2022 at the Osaka International Cancer Institute. After a portion of each sample obtained via EUS‐TA was separated for routine histological evaluation, the residual samples were divided into filter paper and oil blotting paper groups for analysis. Accordingly, filter paper and oil blotting paper were used for the formalin fixation process. The total tissue, nuclear, and cytoplasm areas of each sample were quantitatively evaluated using virtual slides, and the specimen volume and histological diagnosis of each sample were evaluated by an expert pathologist. Results: All cases were cytologically diagnosed as adenocarcinoma. The area ratios of the total tissue, nuclear, and cytoplasmic portions were significantly larger in the oil blotting paper group than in the filter paper group. The frequency of cases with large amount of tumor cells was significantly higher in the oil blotting paper group (33.3%) than in the filter paper group (11.9%) (p = 0.035). Conclusions: Oil blotting paper can increase the sample volume obtained via EUS‐TA on glass slides and improve sampling adequacy for molecular testing. [ABSTRACT FROM AUTHOR]