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The composition dependence of gravitational constant G is measured at the millimeter scale to test the weak equivalence principle, which may be violated at short range through new Yukawa interactions such as the dilaton exchange force. A torsion balance on a turning table with two identical tungsten targets surrounded by two different attractor materials (copper and aluminum) is used to measure gravitational torque by means of digital measurements of a position sensor. Values of the ratios and were and , respectively; these were obtained at a center to center separation of 1.7 cm and surface to surface separation of 4.5 mm between target and attractor, which is consistent with the universality of G. A weak equivalence principle (WEP) violation parameter of at the shortest range of around 1 cm was also obtained. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to apply the principles of the "Milan criteria" to patients undergoing hepatic resection for CRLM and to evaluate the efficacy of prognostic factors., Methods: The medical records of consecutive patients who underwent curative resection for CRLM from April 2007 to April 2019 were retrospectively reviewed. Time to aggressive treatment failure (TATF) was defined as the time interval from the initial surgery until the first unresectable recurrence or recurrence that could only be treated with doublet or lower dose chemotherapy, or death. The risk factors associated with recurrence-free survival (RFS), TSF, TATF, and overall survival (OS) were evaluated., Results: On univariate analysis, the Milan criteria significantly predicted long-term OS, TATF, TSF, and RFS. Moreover, the Milan criteria were able to stratify patients with CRLM into distinct prognostic groups with regard to long-term OS, TATF, TSF, and RFS., Conclusions: Milan criteria, a simple index, are a factor contributing to all the survival time and are a very important factor in discussing the prognosis of CRLM.

Background: Coronary artery aneurysms (CAAs) are increasingly diagnosed on coronary angiography; however, controversies persist regarding their optimal management. In the present study, we analysed the long-term outcomes of patients with CAAs following three different management strategies., Methods: We performed a retrospective review of patient records with documented CAA diagnosis between 2000 and 2005. Patients were divided into three groups: medical management versus percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). We analysed the rate of major cardiovascular and cerebrovascular events (MACCEs) over a period of 10 years., Results: We identified 458 patients with CAAs (mean age 78±10.5 years, 74.5% men) who received medical therapy (N=230) or underwent PCI (N=52) or CABG (N=176). The incidence of CAAs was 0.7% of the total catheterisation reports. The left anterior descending was the most common coronary artery involved (38%). The median follow-up time was 62 months. The total number of MACCE during follow-up was 155 (33.8%); 91 (39.6%) in the medical management group vs 46 (26.1%) in the CABG group vs 18 (34.6%) in the PCI group (p=0.02). Kaplan-Meier survival analysis showed that CABG was associated with better MACCE-free survival (p log-rank=0.03) than medical management. These results were confirmed on univariate Cox regression, but not multivariate regression (OR 0.773 (0.526 to 1.136); p=0.19). Both Kaplan-Meier survival and regression analyses showed that dual antiplatelet therapy (DAPT) and anticoagulation were not associated with significant improvement in MACCE rates., Conclusion: Our analysis showed similar long-term MACCE risks in patients with CAA undergoing medical, percutaneous and surgical management. Further, DAPT and anticoagulation were not associated with significant benefits in terms of MACCE rates. These results should be interpreted with caution considering the small size and potential for selection bias and should be confirmed in large, randomised trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

For pancreatic cancer, the probability of distant metastasis can help choose the best course of treatment. The aim of this study is to establish the efficacy of hydroxyproline as a biomarker for distant metastasis for pancreatic cancer and to clarify the mechanism of EGLN/HIF1A axis that controls the invasion and metastasis. Metabolites (hydroxyproline) and genes (EGLN2 and EGLN3) were identified by metabolome analysis of the serum with pancreatic cancers with and without distant metastasis. The mechanism of EGLN/HIF1A axis including angiogenesis was examined in pancreatic cancer cells. Hydroxyproline associated with these mechanisms was evaluated to suggest the association with overall survival in pancreatic cancer. Decreased expression of EGLN2 and EGLN3 in pancreatic cancer, via the HIF1A and TGF ß1 pathway, was associated with the induction of angiogenic factors, increased vascular invasion, and poor overall patient survival. Hydroxyproline concentrations were regulated via the HIF1A pathway by EGLN2 and EGLN3, and that increased concentrations of hydroxyproline promote the invasion and metastasis of pancreatic cancer cells. These results suggested that the expression of hydroxyproline through the HIF1A pathway induced by EGLN2 and EGLN3 could be a surrogate marker for treatment and might predict distant metastasis in pancreatic cancer., Competing Interests: None., (AJCR Copyright © 2020.)

Background: Granulosa cell tumor (GCT) is a type of ovarian sex cord-stromal tumor with low-grade malignancy, which can recur long after primary resection. All reports on GCTs in the liver describe cases of metastases, while there are no previous reports of primary GCTs originating from the liver. We report a case of GCT, with recurrence of liver metastasis long after ovariectomy, which was subsequently resected by a right trisectionectomy., Case Presentation: A 76-year-old woman presented with a history of surgical resection of an ovarian tumor performed 30 years previously; no details of the tumor were available. When she was 68 years old, an abdominal ultrasound revealed a small liver mass, which was diagnosed as a hepatic hemangioma with slow growth. Outpatient follow-up was discontinued for 5 years, and the patient was not examined again until the age of 76 years. At this point, the tumor had substantially increased in size, and surgical resection was required owing to suspicion of malignancy. The patient was then referred to our hospital. Contrast-enhanced computed tomography (CT) showed a large tumor, approximately 18 cm in size, occupying the right lobe and medial section of the liver. After percutaneous transhepatic portal vein embolization, a right trisectionectomy was performed. The histopathological findings of the resected specimen showed that the tumor cells had "coffee bean-like" nuclear grooves, which are characteristic of a GCT. Acidophilic non-structural Call-Exner bodies were also observed. Inhibin-α, CD99, and CD56 markers of sex cord-stromal tumors were detected on immunohistological examination; all pathology suggested a GCT. We considered the tumor to be a liver metastasis of a previous ovarian GCT that was resected 30 years prior by ovariectomy. There was no recurrence for > 15 months after the hepatectomy., Conclusions: We report a case of a GCT in the liver, which was identified to be a liver metastasis. Right trisectionectomy was subsequently performed for tumor resection. Clinicians should be aware that ovarian GCTs may recur in the liver, and that GCT recurrence may occur long after ovariectomy of the primary ovarian GCT.

Background: Laparoscopic hepatectomy has rapidly evolved and has become a viable alternative to open hepatectomy. However, the dissection of liver parenchyma via the laparoscopic caudal approach (parenchymal transection from the caudal to cranial direction under a laparoscopic caudal view) has several limitations. To avoid these limitations in anatomical hepatectomy along the hepatic vein with the caudal approach, it is important to recognize the "tenting sign of the hepatic vein," which helps to identify the running of the main trunk of the hepatic vein., Technical Presentation: In the bifurcation of the hepatic vein, there is a possibility of splitting of the hepatic vein branch or disorientation between the main trunk and branch. Therefore, it is vital that when the branch is pulled, the main trunk of the hepatic vein appears to be toward the direction of the branch. As a result, the main trunk appears in the direction from the original route to the pseudo route. In the caudal approach, this phenomenon is called "tenting sign of the hepatic vein." Therefore, liver dissection should be performed in the contralateral and cranial sides of the main trunk, with the "tenting sign of the hepatic vein" in mind. This report describes specific cases of the "tenting sign of the hepatic vein.", Conclusion: The "tenting sign of the hepatic vein" from the caudal approach is essential knowledge for safe and reliable anatomical laparoscopic hepatectomy and can lead to expansion of indications in the future.

Titanium- n -butoxide was hydrolyzed in the presence of benzoylacetone, and the resulting solution was concentrated and dried at 120 or 140 °C to obtain transparent amorphous materials. High-energy X-ray diffraction measurement was conducted at the SPring-8 facility, and the reduced pair distribution function, G ( r ) was calculated by Fourier transform of the total structure factor, S ( Q ). The G ( r ) value suggested that the materials are composed of TiO 6 octahedra linked by corner- and edge-sharing. Low temperature thermomechanical analysis (TMA) and differential scanning calorimetry (DSC) were conduced on the materials, where a deflection was detected both in the TMA and DSC curves, revealing the glass transition of the materials. Combined with the previous work based on infrared absorption spectroscopy and gel permeation chromatography, the materials are demonstrated to be a new class of glassy materials composed of linked metal-oxygen polyhedra chelated with organic molecules. The materials are innovative due to the high refractive indices that originate in the metal-oxo oligomers and to the shapability given by their thermoplastic properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To evaluate the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems, we investigated anti-allergic action in mice using IgE-mediated immediate hypersensitivity. Hot water extracts obtained from the roots of Glycyrrhiza uralensis cultivated using two systems were orally administered at a dose of 100 mg/kg as glycyrrhizin (GL) and compared with the commercial crude drug, Glycyrrhizae Radix. Both the artificial hydroponic and artificial hydroponic-field hybrid cultivated root extracts showed anti-allergic effects on IgE-mediated immediate hypersensitivity in mice, as did the commercial crude drugs. These results highlight the potential for artificially cultivated roots of Glycyrrhiza uralensis to be used as an alternative medicinal source.

Background: Morbidity following pancreaticoduodenectomy (PD) has been reported to remain high. This study sought to measure the peak Hounsfield units (HUs) of visceral attenuation in patients undergoing PD and to assess the quality of adipocytes by comparing these measurements with perioperative factors., Methods: Patients undergoing PD were retrospectively identified (n = 108). Abdominal perimeter, subcutaneous fat area (SFA), visceral fat area (VFA), and peak HU of the VFA were measured. Logistic regression analysis was used to identify independent predictors of postoperative pancreatic fistula (POPF) or complications. Histopathological examination was performed for qualitative diagnosis of the stromal tissue., Results: The overall rate of POPF was 16%, and severe complications occurred in 23% of the cases. A criterion for peak HU of the VFA only independently predicted POPF (p = 0.007) in the multivariate analysis. A criterion for peak HU of the VFA (p = 0.015) was associated with an increased rate of postoperative severe complications in the univariate analysis. The peak HU of the VFA was significantly correlated with abdominal perimeter (p < 0.001) and VFA (p < 0.001). The peak HU of the VFA was significantly correlated with adipocyte diameter (p < 0.001) and the ratio of stromal connective tissue area around the adipocytes (p < 0.001)., Conclusion: The peak HU of the VFA was an independent factor contributing to severe complications, including POPF after PD. It reflects the amount of stromal connective tissue around the adipocytes., (© 2020 S. Karger AG, Basel.)

The patient was a 56-year-oldwoman. She presentedto a nearby doctor with a chief complaint of dysphagia andwas diagnosed with esophageal cancer by upper gastrointestinal endoscopy, resulting in a referral to our hospital. Upper gastrointestinal endoscopy revealeda semicircular type 1 lesion 29 to 32 cm from the incisors, andshe was diagnosedwith squamous cell carcinoma by biopsy. Computedtomography (CT)andpositron emission tomography(PET)scans revealedthe enlargement and accumulation of lymph nodes along the lesser curvature of the stomach; thus, she was diagnosed with metastasis. In addition, multiple accumulations were found in the 7th cervical vertebrae as well as in the 1st, 3rd, 4th, and 8th thoracic vertebrae, leading to the diagnosis of bone metastasis. She was finally diagnosed with middle intrathoracic esophageal cancer T2N1M1, Stage Ⅳ; thus, we performedchemorad iotherapy(CRT)with 5-FU andCDDP (FP). The main lesion was markedly reduced in upper gastrointestinal endoscopy after CRT, and no apparent malignancy was found in endoscopic biopsy, so the diagnosis was endoscopic complete response. The CT scan also showed marked reductions in both the main lesion and the lymph nodes. As for the bone metastasis, some areas of bone consolidation remained, but they were diagnosed as partial responses since they were shrunk. Since then, FP has been continuously administeredon a regular basis andit has been about 2 years without any appearance of new lesions or re-exacerbation.

Human norovirus (HuNoV) GII.P17-GII.17 (Kawasaki2014 variant) reportedly emerged in 2014 and caused gastroenteritis outbreaks worldwide. To clarify the evolution of both VP1 and RNA-dependent RNA polymerase ( RdRp ) regions of GII.P17-GII.17, we analyzed both global and novel Japanese strains detected during 2013-2017. Time-scaled phylogenetic trees revealed that the ancestral GII.17 VP1 region diverged around 1949, while the ancestral GII.P17 RdRp region diverged around 2010. The evolutionary rates of the VP1 and RdRp regions were estimated at ~2.7 × 10 -3 and ~2.3 × 10 -3 substitutions/site/year, respectively. The phylogenetic distances of the VP1 region exhibited no overlaps between intra-cluster and inter-cluster peaks in the GII.17 strains, whereas those of the RdRp region exhibited a unimodal distribution in the GII.P17 strains. Conformational epitope positions in the VP1 protein of the GII.P17-GII.17 strains were similar, although some substitutions, insertions and deletions had occurred. Strains belonging to the same cluster also harbored substitutions around the binding sites for the histo-blood group antigens of the VP1 protein. Moreover, some amino acid substitutions were estimated to be near the interface between monomers and the active site of the RdRp protein. These results suggest that the GII.P17-GII.17 virus has produced variants with the potential to alter viral antigenicity, host-binding capability, and replication property over the past 10 years., (Copyright © 2019 Matsushima, Mizukoshi, Sakon, Doan, Ueki, Ogawa, Motoya, Tsukagoshi, Nakamura, Shigemoto, Yoshitomi, Okamoto-Nakagawa, Suzuki, Tsutsui, Terasoma, Takahashi, Sadamasu, Shimizu, Okabe, Nagasawa, Aso, Ishii, Kuroda, Ryo, Katayama and Kimura.)

As a part of the investigation of the safety and efficacy of the cultivated Coptis japonica rhizome extracts using an artificial hydroponic cultivation system, the mutagenetic and anti-allergic activities were evaluated. Some extracts of commercial crude drugs of Coptis sp. were also evaluated for the comparison. None of the extracts showed a significant mutagenicity in Salmonella typhimurium TA102 by the Ames tests, but all the extracts showed in S. typhimurium TA98. The extracts of the hydroponically cultivated rhizomes showed anti-allergic activities against contact hypersensitivity as well as those of commercial crude drugs of Coptis sp. These results suggested the potential of the hydroponically cultivated rhizomes as one of the alternative sources for the medicinal usage.

Background: The aim of the present study was to investigate risk factors for the development of grade C compared to grade B cases of postoperative pancreatic fistula (POPF)., Materials and Methods: Clinicopathological data from 43 patients who developed grade B or C POPF were retrospectively analyzed. The following types of factors were analyzed: Patient-related, surgery-related, and pancreas-related, including the value of the drain amylase and the detection of gram-negative rod bacteria within the first 7 postoperative days (PODs)., Results: Univariate analysis showed that male sex (p=0.0492) and detection of gram-negative rods within the first 7 PODs (p=0.0010) were risk factors for development of grade C POPF. Only detection of gram-negative rods within the first 7 PODs was a significant factor after multivariate analysis (p=0.0027)., Conclusion: Sensitive and specific predictive criteria for early detection of grade C POPF should be developed to allow for a management approach appropriately tailored to this condition., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pancreatic vascular malformation causes epigastric pain, pancreatitis, portal vein hypertension, bleeding, and rupture. It is a rare disease, with most pancreatic vascular malformations being arteriovenous malformations (AVMs) and the other types of malformations being rare. We report a case of capillary lymphatic malformation (CLM) in the pancreatic uncinate process., Case Presentation: A 74-year-old woman, who presented with complaints of repeated upper abdominal pain, was admitted to our institution. Contrast-enhanced dynamic computed tomography (CT) scan revealed that the tumor in the pancreatic uncinate process had a poor contrast effect in the arterial phase and a small contrast effect in the equilibrium phase, which are suggestive of a benign disease-like vascular malformation. However, we suspected that it could possibly be a malignant tumor because the tumor size tended to increase over time; thus, we decided to perform a surgery. We resected the tumor through a partial resection of the pancreas. Macroscopically, the cut surface of the tumor had a spongioid appearance. Histopathological examination findings showed a mixed shape of small capillaries and lymphatic ducts. The patient was diagnosed with CLM according to the International Society for the Study of Vascular Anomalies (ISSVA) classification, based on the histological appearance and immunostaining findings. The postoperative course of the patient was uneventful., Conclusions: We reported a case of pancreatic vascular malformation, specifically a CLM, which was completely resected through a partial pancreatectomy.

Background: The combination of major hepatectomy and pancreatoduodenectomy (PD), that is, a hepatopancreatoduodenectomy (HPD), is the only curative treatment for bile duct cancer with extensive horizontal tumor spread invading both the hepatic hilum and the intrapancreatic bile duct. However, this aggressive procedure remains controversial with regard to the balance between the survival benefit and high risk of mortality and morbidity, especially the risk for postoperative hepatic failure and postoperative pancreatic fistula. Here, we describe the efficacy of a novel modified technique of HPD with delayed division of the pancreatic parenchyma for hilar cholangiocarcinoma, and focus on the surgical technique and the short-term outcomes, with a representative case., Technical Presentation: This new surgical technique involves dissection of the pancreatic parenchyma and relevant mesoduodenum at the final step after dissecting the required parts on the inferior side and superior side of the tumor, enabling excision of the resected specimen. This technique described herein can prevent saponification of the resected surface of the pancreas by dissecting the pancreatic parenchyma toward the latter half of the surgical procedure as much as possible. The results suggest that there may also be a relationship between this technique and the prevention of postoperative pancreatic fistula., Conclusion: This new surgical technique of HPD may be able to prevent postoperative pancreatic fistula by performing intraoperative dissection of the pancreatic parenchyma as late as possible, which in turn, may improve the safety of HPD.

Background: Various approaches to hepatectomy have been proposed for cT2 gallbladder cancers (GBC), but the optimal management strategy remains unclear. The aim of this study is to assess the effectiveness of using an indocyanine green (ICG)-based intraoperative navigation system during hepatic resection for cT2 GBC., Methods: From September 2007 to December 2017, 24 consecutive patients diagnosed with cT2 GBC underwent hepatic resection using ICG navigation. After cannulation of the cholecystic artery, ICG diluted with dissolution liquid was injected and ICG fluorescence illumination was visualized with the HyperEye Medical System. And additional histopathological examination was performed on the most recent 15 of the 24 patients for detection of microscopic liver metastasis., Results: For all patients, the disease-free survival rate was 59.1% at 5 years and overall survival rate was 86.2% at 5 years. Microscopic liver metastasis was detected in the resected liver in 3 (20%) of 15 patients, whose site of liver was S6, S5, and S5, respectively. The weight of the liver resected using ICG navigation was significantly smaller than that of S4a/S5 segmentectomy (P < 0.0001)., Conclusion: Resected hepatic lesion using ICG imaging was possible to perform hepatectomy including liver micro-metastasis without excess or deficiency. This procedure might be novel intraoperative imaging method to provide valuable information on the optimal surgical approach to cT2 GBC.

Purpose: Postoperative superficial surgical site infection is a major complication in hepatobiliary-pancreatic surgery. We aimed to compare the efficacy of subcuticular sutures versus staples for skin closure in preventing superficial surgical site infection in hepatobiliary-pancreatic surgery., Methods: Consecutive patients who underwent hepatobiliary-pancreatic surgery at our hospital from October 2006 to March 2011 and from April 2012 to March 2015 were reviewed retrospectively. Superficial surgical site infection incidence was evaluated in patients who received subcuticular sutures and those who received staples for skin closure. Propensity score matching analysis was used to adjust bias from confounding factors., Results: A total of 691 patients were included. Patients with skin staple closures (n = 346) were compared with patients with subcuticular suture closures (n = 345). After a propensity score matching analysis, a significant difference in superficial surgical site infection incidence was found between the skin stapler group (11.3%) and subcuticular sutures group (2.6%). The same comparison was performed by a subgroup analysis and supported this finding in patients after hepatectomy without biliary reconstruction, pancreatoduodenectomy, or open laparotomy surgeries and in patients with body mass index < 25., Conclusions: Subcuticular suturing after hepatobiliary-pancreatic surgery was more efficacious in reducing postoperative superficial surgical site infection incidence than staples for skin closure.

Background: The aim was to analyze hepatic hypertrophy after portal vein embolization (PVE) and Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) to determine whether clinical circumstances associated with major hepatic resections correlated with remnant growth., Methods: Data was abstracted from a retrospectively maintained database on 27 patients undergoing hepatic resection followed by PVE and the ALPPS procedure between October 1, 2007 and December 31, 2016. The increasing rate of liver volume and remnant liver LU15 was defined as the percentage-point difference between the liver volume and remnant liver LU15 before and after the intervention or surgery. And correlation between kinetic growth rate (KGR) of liver and future remnant liver volume or remnant liver LU15 was analyzed., Results: The degree of hypertrophy (DH) of volume and LU15 was significantly greater after ALPPS (volume: 40.3% and LU15: 65.0%) than after PVE (volume: 22.7% and LU15: 48.8%) ( P  < 0.05). KGR of volume and LU15 was significantly greater after ALPPS (volume: 19.0 cm 3 /day and 2.00%/day) (LU15: 0.61 /day and 1.82%/day) than after PVE (volume: 3.89 cm 3 /day and 0.42%/day) (LU15: 0.19 /day and 0.63%/day) ( P  < 0.001). An inverse correlation between KGR and initial remnant liver volume was observed. And a positive correlation between KGR and LU15 was observed., Conclusion: Future remnant liver volume and KGR was greater after the ALPPS procedure than after PVE. Liver hypertrophy is related to the expected remnant liver volume and total liver function. This study suggested that total liver function and initial remnant liver volume might be a new indication of hepatectomy after PVE and ALPPS in the case of insufficient remnant liver volume., Competing Interests: This research data was approved by Tokyo Medical Universoty Hachioji Medical Center Ethics committee.This research data had consent of publications from all patents.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose: To genetically explore the fusion protein gene (F) in human parainfluenza virus type 1 (HPIV1) and type 3 (HPIV3) strains, we analysed them in patients with acute respiratory infections in Eastern Japan from 2011 to 2015., Methodology: We constructed phylogenetic trees based on the HPIV and HPIV3 F gene using the maximum likelihood method and conducted P-distance and selective pressure analyses. We also predicted the linear epitopes of the protein in the prototype strains. Furthermore, we mapped the amino acid substitutions of the proteins., Results: Nineteen strains of HPIV1 and 53 strains of HPIV3 were detected among the clinical acute respiratory infection cases. The phylogenetic trees indicated that the HPIV1 and HPIV3 strains were classified into clusters II and III and cluster C, respectively. The P-distance values of the HPIV1 and HPIV3 F genes were <0.03. Two positive selection sites were inferred in the HPIV1 (aa 8 and aa 10), and one positive selection site was inferred in the HPIV3 (aa 108), but over 10 negative selection sites were inferred. Four epitopes were predicted for the HPIV1 prototype strains, while five epitopes were predicted for the HPIV3 prototype strain. A positive selection site (aa 108) or the HPIV3 F protein was involved in the predicted epitope. Additionally, we found that an amino acid substitution (R73K) in the LC76627 HPIV3 strain presumably may affect the resistance to neutralization by antibodies., Conclusion: The F gene of HPIV1 and HPIV3 was relatively well conserved in the eastern part of Japan during the investigation period.

The reported patient was a 90-year-old woman with anorexia. She was diagnosed with advanced gallbladder cancer that occurred concurrently with stomach cancer. Subsequent to intestinal bypass surgery, S-1(80mg/day)was administered for 14 days, followed by 7 days of rest for one course. Tumor marker levels returned to normal after 4 months. Computed tomography results indicated that, in regard to the gallbladder cancer, the patient had stable disease after 8 months. In addition, gastroscopy revealed a complete response of the gastric cancer after a year. The patient was able to continue treatment as an outpatient until she experienced aspiration pneumonia. The administration of S-1 was terminated after 4 years and 4 months. Treatment with S-1 monotherapy is considered safe for elderly patients, and has the additional benefit that it is deliverable as an outpatient treatment.

The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.

Purpose: This paper describes the technical details of the new indwelling catheter system, which we refer to as System-i, and provides an overview of our experience with this system at our institution., Materials and Methods: The system is implanted via the left brachial artery. The feeding artery of the tumor is catheterized at each treatment, and the system can be used for multiple treatments via more than one feeding artery. Between January 2004 and January 2013, System-i was used to administer 398 treatments in 30 patients with hepatocellular carcinoma (HCC). The technical aspects and outcomes of treatment procedures were evaluated., Results: Implantation was successful in all cases. System-i was used for a median number of 11 treatments per patient over a median period of 5.7 months, and 71.6 % of all treatments were administered on an outpatient basis., Conclusion: System-i provides an effective and safe method for selective catheterization of feeding arteries for administration of transcatheter arterial chemoembolization or infusion in patients with HCC. Treatment regimens can be individualized without limiting the number of treatments or treatment locations, and patients can be treated on an outpatient basis.

This study performed a detailed genetic analysis of the glycoprotein (G) gene of respiratory syncytial virus (RSV) detected in 50 Japanese children with acute respiratory infection (ARI) in the 2009/2010 season. A phylogenetic tree constructed by the neighbour-joining method showed that 34 and 16 of the RSV strains could be classified into subgroups A and B, respectively. Strains belonging to subgroups A and B were further subdivided into GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%). The deduced amino acid sequences implied that a relatively high frequency of amino acid substitutions occurred in the C-terminal 3rd hypervariable region of the G protein in these strains. In addition, some positively selected sites were estimated. The results suggest that RSV with genotypes GA2 and BA was associated with ARI in Japanese children in 2009/2010.

Background: Operative mortality after left ventricular assist device (LVAD) implantation is heavily influenced by patient selection and the technical difficulty of surgery. However, how we treat our patients and LVAD setting may affect the patient outcome beyond this period. We postulated that the presence of echocardiographic variables 1 month after surgery suggesting appropriate degree of LV unloading and an adequate forward flow would be important in determining clinical outcomes after the initial successful LVAD implantation., Methods and Results: We retrospectively analyzed various variables in echocardiographic examinations performed 30 days after LVAD implant in 76 consecutive patients receiving continuous flow device for their association with a compound end point (90-day mortality, readmission for heart failure, or New York Heart Association class III or higher at the end of the 90-day period). The echocardiographic associations examined included estimated LVAD flow, with and without native LV contribution, interventricular septal position, the status of aortic valve opening, an estimated left atrial pressure (ELAP), the mitral flow E-wave deceleration time, and the ratio of deceleration time to E-wave velocity (mitral deceleration index [MDI]). Four patients died during the 30- to 90-day period, 6 patients were readmitted for heart failure, and 25 patients were considered to have New York Heart Association class III or higher at the end of the 90-day period. Variables associated with adverse outcome included increased ELAP (odds ratio, 1.30 [1.16-1.48]; P<0.0001), MDI <2 ms/[cm/s] (odds ratio, 4.4 implantation [1.22-18]; P=0.02) and decreased tricuspid lateral annulus velocity (odds ratio, 0.70 implantation [0.48-0.95]; P=0.02). A leftward deviation of interventricular septum was associated with a worse outcome (odds ratio, 3.03 implantation [1.21-13.3]; P=0.01)., Conclusions: Mortality and heart failure after LVAD surgery appear to be predominantly determined by echocardiographic evidence of inefficient unloading of the left ventricle and persistence of right ventricular dysfunction. Increased estimated LA pressure and short MDI are associated with worse mid term outcome. Leftward deviation of the septum is associated with worse outcome as well.

The present study was undertaken to investigate the effect of ethanol on the sleep-wake cycle in normal rats and sleep-disturbed rats. In normal rats, no significant difference was observed by ethanol in sleep latency, total awake time and total non-rapid eye movement (NREM) sleep time, except for total REM sleep time. On the other hand, in sleep-disturbed rats, ethanol at doses of 1 and 2 g/kg caused significant decreases in sleep latency and total wake time, and an increase in total NREM sleep time. In addition, ethanol showed a significant increase in delta activity in the sleep-disturbed model rat, different from triazolam. These results suggested that ethanol had not only a hypnotic but also a sleep-maintaining effect in sleep-disturbed rats at reasonable blood ethanol concentrations.

The present study was performed to investigate the effects of kavain on the sleep-wake cycle in comparison with that of rilmazafone and diphenhydramine using sleep-disturbed rats. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were implanted into Wistar rats. Total awake time, non-rapid eye movement (non-REM) sleep and rapid eye movement (REM) sleep were measured for 6 h. Kavain and rilmazafone showed a significant shortening in sleep latency, decreased awake time, and increased non-REM sleep time. On the other hand, significant shortening of the sleep latency was observed following the administration of diphenhydramine, while no effects were observed on the awake and non-REM sleep time. Moreover, kavain showed a significant increase in delta activity during non-REM sleep in sleep-disturbed rats, whereas a significant decrease in delta power during non-REM sleep was observed with rilmazafone. These results clearly indicate that kavain is a compound with not only hypnotic effects, but also sleep quality-enhancement effects.

The present study was performed to investigate the effects of histamine H(1)-antagonists on the sleep-awake state in rats placed on a grid suspended over water in comparison with rats placed on sawdust. When rats were placed on the grid suspended over water, significant increases in the awake time and decreases in non-rapid eye movement (non-REM) sleep time were observed compared with in rats on sawdust, even when measured hourly for 6 h. Diphenhydramine, chlorpheniramine and promethazine caused a significant decrease in the awake time and increase in non-REM sleep time in rats placed on the grid suspended over water for 1-2 h and/or 2-3 h after administration. On the other hand, in rats placed on sawdust, no significant differences were observed in the awake time and non-REM sleep time with diphenhydramine and chlorpheniramine compared with the control. Different from these two drugs, promethazine caused a significant decrease in the awake time and increase in non-REM sleep time 1-2 h and 2-3 h after administration even when rats were placed on sawdust at a relatively high dose. These results clearly indicate that histamine H(1)-antagonists had potent effects on decreasing the awake time and increasing non-REM sleep time under the conditions of an activated histaminergic system.

In the present study, the characteristics of the sleep features of amitriptyline, mexiletine, and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyradine-1(2H)-carbox-amide (BCTC) were studied. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscles of rats for electroencephalogram (EEG) and electromyogram (EMG) measurements, respectively. EEG and EMG were recorded with an electroencephalograph, and SleepSign ver. 2.0. was used for sleep-wake state analysis. Recordings were performed from 11:00 to 17:00. Amitriptyline caused significant decreases in sleep latency and total wake time and an increase in total non-rapid eye movement (non-REM) sleep time. Mexiletine caused a significant decrease in sleep latency, but no significant effect was observed in total wake time and total non-REM sleep time. On the other hand, BCTC, which is an antagonist of transient receptor potential vaniloid 1 (TRPV1), showed no significant effect on sleep latency, total wake time, total non-REM sleep time, and total REM sleep time. From these results, it can be concluded that a TRPV1 antagonist may become a useful drug for neuropathic pain without sedative side effects in the daytime, different from amitriptyline and mexiletine.

Introduction: Descending necrotising mediastinitis is a form of mediastinitis caused by odontogenic infection or deep cervical infections, which spreads to the mediastinum via the cervical fascial planes. Despite the increased use of CT scan as a diagnostic aid and the improvement in antibiotics, mortality in patients with descending necrotising mediastinitis remains high, reported between 25 and 40% in the literature. Surgical management and optimal form of mediastinal drainage remain controversial., Patients and Methods: We have treated three patients with descending necrotising mediastinitis at our institution. Two patients were male and one was female with mean age 54.3+/-12.5 years. One of the patients was a known diabetic. The primary oropharyngeal infection was Ludwig's angina, odontogenic abscess and parapharyngeal abscess. All patients underwent mediastinal drainage, one through midsternotomy and two through right thoracotomy in addition to cervical drainage. All the three patients had mixed aerobic and anaerobic infection., Results: There was no perioperative mortality. Mean ICU stay was 32 days (12-53 days). All three patients had septicaemic shock requiring prolonged inotropic support. Two patients required tracheostomy because of prolonged ventilation. All the patients had recurrent abscesses and collections either in neck or in chest requiring drainage either surgically or percutaneously under CT scan or ultrasound guidance, thus decreasing the need of repeated surgical procedures., Conclusion: Descending necrotising mediastinitis is a potentially fatal condition. Early diagnosis, prompt surgical drainage, monitoring of disease process, appropriate medical management in an intensive care unit and a multi-disciplinary approach can significantly reduces the mortality in this otherwise fatal condition. Percutaneous drainage of recurrent abscesses and collections can decrease the need of repeated surgical procedures in these critically ill patients.

Between May14 and 18, 2001, there was an outbreak of acute gastroenteritis involving 45 school children out of a total of 107 (aged 11-12 years) attending a 3-day school trip. The epidemic curve characterized by a rapid onset and decline with a single peak incidence over a 5-day period resembled the pattern typical of a food-borne gastroenteritis outbreak. Epidemiological and virological investigations concluded, however, that this outbreak was caused by a single strain of serotype G2 group A rotavirus spreading to schoolmates from the primary case-pupil who had already been ill at the start of the trip. Efficient person-to-person transmission was likely to have occurred due to prolonged and close contacts under the conditions typical of such school trips. This study emphasizes the importance of including group A rotavirus infection as a possible cause of gastroenteritis outbreaks even in older children and adults., (Copyright 2004 Wiley-Liss, Inc.)

The effect of Zn2+ on the O2- generation and change in intracellular Ca2+ concentration ([Ca2+]i) of rat peritoneal neutrophils was studied. Zymosan (serum-treated zymosan (STZ))-induced O2- generation was inhibited by Zn2+ at concentrations as low as 10 microM. A large amount of the inhibition was observed in the absence of extracellular Ca2+ but the inhibition could not be restored by increasing the extracellular Ca2+ concentration, indicating that Zn2+ does not necessarily inhibit the O2- generation competitively with extracellular Ca2+. In the absence of extracellular Ca2+, Zn2+ inhibited STZ-induced transient increase in [Ca2+]i in the concentration range that evoked a marked inhibition in the O2- generation. On the other hand, Zn2+ did not inhibit significantly STZ-induced uptake of 45Ca2+ from extracellular medium by the cells. From these results, it is suggested that Zn2+ inhibits STZ-induced release of Ca2+ from intracellular storage sites, resulting in the suppression of the activation mechanism of neutrophils.

The effect of Pb2+ on serum-treated zymosan (STZ)-induced O2 consumption of rat peritoneal neutrophils was studied. Pb2+ was found to mimic effectively the enhancing action of Ca2+ on the O2 consumption depending on the concentration up to about 80 microM. However, at concentrations over 80 microM, Pb2+ inhibited the O2 consumption. The enhancing effect of Pb2+ on the O2 consumption was further examined using the intracellularly Ca2(+)-depleted neutrophils. Pb2+ also enhanced the O2 consumption of the Ca2(+)-depleted cells as effectively as Ca2+. The Pb2(+)-enhanced O2 consumption of the Ca2(+)-depleted cells was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) based on its calmodulin antagonistic action. The effect of Pb2+ on the activity of activator-deficient 3',5'-cyclic nucleotide phosphodiesterase (PDE), a calmodulin-dependent enzyme, was examined. Pb2+ activated PDE as effectively as Ca2+ only in the presence of calmodulin. The Pb2(+)-activated PDE activity was also inhibited by W-7 only in the presence of calmodulin. These results indicated that Pb2+ could replace Ca2+ in the activation process(es) of the respiratory burst, suggesting a possible involvement of calmodulin in the enhancing mechanism of the O2 consumption by Pb2+.