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Using a combination of photostimulated desorption and resonance-enhanced multiphoton ionization methods, the behaviors of OH radicals on the surface of interstellar ice analog was monitored at temperatures between 54 and 80 K. The OH number density on the surface of ultraviolet (UV)-irradiated compact amorphous solid water gradually decreased at temperatures above 60 K. Analyzing the temperature dependence of OH intensities with the Arrhenius equation, the decrease can be explained by recombination of two OH radicals, which is rate-limited by thermal diffusion of OH. The activation energy for surface diffusion was experimentally determined for the first time to be 0.14 +/- 0.01 eV, which is larger than or equivalent to those assumed in theoretical models. This value implies that the diffusive reaction of OH radicals starts to be activated at approximately 36 K on interstellar ice., 5 figures, Accepted to ApJL

Introduction For patients who have acute severe cholecystitis, urgent/early biliary drainage followed by delayed/elective laparoscopic cholecystectomy is recommended according to the Tokyo Guidelines 2018. Percutaneous transhepatic gallbladder drainage is an established technique. Recently, transmural gallbladder drainage under the guidance of endoscopic ultrasonography (EUS-GBD) was reported as a safe alternative. During surgery, fluorescence imaging using indocyanine green (ICG) has been increasingly used for visualizing the bile ducts. Herein, we report a sequential treatment approach which ensures safety without impairing normal activities before cholecystectomy: EUS-GBD followed by laparoscopic cholecystectomy using ICG fluorescence imaging. Materials and surgical technique A 66-year-old man with acute cholecystitis underwent urgent EUS-GBD and had the drainage tube placement through the duodenum into the gallbladder. During 2.5 months of the waiting period, he had no clinical troubles. After insertion of a laparoscope, we found a structure between the gallbladder and the duodenum. We injected 0.025 mg/mL of ICG into the nasobiliary drainage tube (placed in the gallbladder through the duodenum) and confirmed that the structure was a fistula. After removing the tube, the fistula was divided using a surgical stapler under the guidance of fluorescence imaging. The cystic and common bile ducts were also clearly visualized as fluorescence. Discussion We reported a safe sequential treatment approach for the patient who required biliary drainage: EUS-GBD followed by laparoscopic cholecystectomy under the guidance of ICG fluorescence imaging. This sequential approach may improve patients' satisfaction with respect to quality of life during the waiting period and may ensure the safety of laparoscopic cholecystectomy.

Metabolism is a critical regulator of cell fate determination. Recently, the significance of metabolic reprogramming in environmental adaptation during tumorigenesis has attracted much attention in cancer research. Recurrent mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes have been identified in several cancers, including intrahepatic cholangiocarcinoma (ICC). Mutant IDHs convert α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which affects the activity of multiple α-KG-dependent dioxygenases including histone lysine demethylases. Although mutant IDH can be detected even in the early stages of neoplasia, how IDH mutations function as oncogenic drivers remains unclear. In this study, we aimed to address the biological effects of IDH1 mutation using intrahepatic biliary organoids (IBOs). We demonstrated that mutant IDH1 increased the formation of IBOs as well as accelerated glucose metabolism. Gene expression analysis and ChIP results revealed the upregulation of platelet isoform of phosphofructokinase-1 (PFKP), which is a rate-limiting glycolytic enzyme, through the alteration of histone modification. Knockdown of the Pfkp gene alleviated the mutant IDH1-induced increase in IBO formation. Notably, the high expression of PFKP was observed more frequently in patients with IDH-mutant ICC compared to in those with wild-type IDH (p

Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative drainage technique for endoscopic retrograde cholangiopancreatography (ERCP) 1 . EUS-BD can be divided into two main categories. The first category is the transduodenal route, for example, EUS-guided choledochoduodenostomy (CDS). The second is transgastric, for example, EUS-guided hepaticogastrostomy (HGS). In addition, EUS-guided gallbladder drainage (GBD) can be performed from both routes. Among these procedures, technical tips can be divided into four steps. The first category is puncturing the biliary tract. The second is guidewire insertion, followed by tract dilation. The final step is stent deployment. Successful tract dilation is the most important among these steps. To date, various techniques have been reported for tract dilation including graded, balloon, or electrocautery dilation 2 3 4 . To prevent bile leakage during EUS-BD, a simple dilation technique may be used. The electrocautery dilation technique can certainly dilate the biliary or luminal wall; however, bleeding may occur around the dilation site due to its burning effects. To overcome this, we have developed a novel fine gauge electrocautery dilator device 5 . An experimental study was performed before clinical use of this novel electrocautery dilator. In this technical view, we describe the results of our experimental study and some technical tips for tract dilation in EUS-BD using this novel electrocautery dilator.

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.

We aimed to investigate the diagnostic accuracy of multidetector-row computed tomography (MDCT), mapping biopsy, and other imaging modalities to predict the longitudinal extension and depth of invasion of extrahepatic cholangiocarcinoma at possible surgical ductal margins. Of 102 patients with surgical resection of extrahepatic cholangiocarcinoma between January 2010 and October 2015, 32 evaluated by multidetector-row computed tomography (MDCT) performed before biliary drainage and mapping biopsy were enrolled. Mapping biopsies were performed at 74 sites to determine the resection point of the bile duct (at 74 possible surgical ductal margins). Diagnostic accuracy was evaluated by histopathology. The diagnostic accuracy of MDCT for longitudinal cancer spread was 79.7%, that of biopsy was 73.0%, and combining the two modalities showed highest accuracy (83.8%). The depth of tumor invasion could be predicted by combination of the ductal wall thickness and contrast enhancement on MDCT, that is, at 11 of 13 sites (84.6%) with submucosal invasion, ductal wall thickness was > 2.5 mm with high contrast enhancement. MDCT demonstrated highest accuracy of diagnosing longitudinal extension at possible surgical ductal margins in patients with extrahepatic cholangiocarcinoma. The depth of tumor invasion could be predicted by ductal wall thickness and contrast enhancement of MDCT.

Highlight Ogura and colleagues present a novel electrocautery dilation device for endoscopic ultrasound-guided procedures. The distal end of the outer dilator contains a 3-Fr metal tip, allowing a smaller burning effect than with conventional devices. This novel device may have clinical impact for endoscopic ultrasound-guided procedures as tract dilation device.

Pancreatic cystic lesions (PCLs) are increasingly identified with the widespread use of imaging modalities. The precise diagnosis of PCLs remains a challenge despite the use of CT, MRI, and EUS-FNA. Confocal laser endomicroscopy (CLE) is a new endoscopic imaging modality that provides real-time, very high magnification images. A smaller CLE probe, which can be passed through a 19-gauge FNA needle, is now available. Needle-based CLE during EUS has recently been examined to evaluate PLCs, and the specific criteria of nCLE for the diagnosis of PLCs have been proposed.

Background/aims To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. Methods A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. Results The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). Conclusions Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.

For highly precise positioning of land vehicles, in this paper, we present an integration method of the low cost MEMS (Micro Electro Mechanical Systems) INS (Inertial Navigation System), GNSS (Global Navigation Satellite Systems) and vehicle speed information. In this paper, we develop the MEMS INS/GNSS/Vehicle Speed (VS) integration system by extending and refining our previous work [1]. The VS is the vehicle speed obtained by counting the wheel rotation of the land vehicle. In the system, so-called the loosely coupled mechanization is applied. Thus the three dimensional position, velocity, attitude of the vehicle and the three dimensional accelerometer and gyro biases are estimated by the Kalman filter by using the measurement of GNSS and VS. And the estimated (predicted) INS errors are fed back to the INS calculations. Additionally, in the proposed method, the scale factor error of VS is estimated by the Kalman filter simultaneously. Moreover, since the direction of the tire, i.e. the direction of VS is not always parallel to the direction of the body by a small angle due to a shake of the body and misalignment of the INS, the difference between them is also simultaneously calibrated in the system. The experiments have been carried out on country roads. Throughout the experiments, the proposed method can effectively estimate the IMU errors and consequently provide accurate navigation.

Two kinds of new silicon actuators, cantilever and twisted-beam, based on pn diode actuation principle are presented. The space gap that is absolutely needed in conventional electrostatic MEMS actuators is replaced by a depletion layer in reversely-biased pn diode. The strong electric field generated in the depletion layer forces a silicon microstructure to vibrate. The microstructure causes a large deflection at resonance. This actuator eliminates a narrow gap between driving electrodes. Consequently, the silicon actuators maintain to be of high reliability for a long period.

Recent advances in hepatology have included a new and effective treatment of viral hepatitis, with an increased need for the assessment of liver function and histology. At the same time, there have been a growing number of endoscopic procedures that are pertinent to patients with liver disease. It would be ideal if the assessment and treatment of liver disease and portal hypertension could be performed and assimilated by the liver/gastrointestinal specialist. The authors like to consider this area of integration or overlap of endoscopic procedures within the practice of hepatology as endo-hepatology.

Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT(1A) receptors in vitro. However, it has still been unclear whether this in vitro effect is reflected in in vivo, and what the active ingredients are. The purpose of the present study is to find the active ingredient in YKS and to demonstrate the effect in in vivo. In the present study, we first studied the effect of YKS and UH on aggressiveness and sociality in socially isolated mice. YKS and UH ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT(1A) receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS. These results suggest that the effect of YKS is mainly attributed to UH, and the active ingredient is contained in UH. To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635. These lines of results suggest that GM in UH is potent 5-HT(1A) receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice.

Introduction: Selective cannulation fails in approximately 3 % of endoscopic retrograde cholangiography (ERC) procedures. An endoscopic ultrasound-guided rendezvous technique (EUS – RV) may salvage failed cannulation. The aims of the current study were to determine the safety and efficacy of EUS – RV. Methods: A total of 40 patients underwent salvage EUS – RV. EUS – RV was attempted immediately after failed biliary cannulation. A dilated intra- or extra-hepatic biliary duct (IHBD or EHBD) was punctured from the stomach or the small intestine under EUS guidance followed by cholangiography and antegrade manipulation of the guide wire into the small intestine. Finally, the echoendoscope was exchanged for an appropriate endoscope and biliary cannulation was achieved over or adjacent to the guide wire. Result: EUS–RV appears safe and effective and may be considered as a primary salvage technique after failed cannulation. Antegrade manipulation of the guide wire into the small intestine was achieved in 29 of 40 patients (73 %; EHBD 25 /31 and IHBD 4/9). The reasons for failure were inability to advance the guide wire through an obstruction or a native ampulla. Re-attempt at ERC immediately after failed EUS – RV was made in seven of the 11 patients, and was successful in four. The remaining seven patients underwent percutaneous drainage within 3 days. Complications occurred in five patients (13 %), including pancreatitis, abdominal pain, pneumoperitoneum, and sepsis/death, which was unlikely to be related to the procedure. Conclusion: EUS – RV is safe and effective and should be considered as a primary salvage technique after failed cannulation. Immediate re-attempt at ERC after failed EUS – RV is warranted, as EUS-guided cholangiogram can facilitate biliary cannulation in some cases. Finally, prompt alternative biliary drainage should be available.

Background: The renin–angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth. Methods: We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs). Results: Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis. Conclusions: The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

The experimental feasibility was investigated for the resonant scattering of monoenergetic neutrinos emitted in the two-body β decay. A simple general formula shows that the resonance cross section can be as large as of the order of 10 −17 cm 2 . The Mossbauer setup using a solid crystal was examined with a focus on the electronic structure of the emitter and the absorber. Based on realistic calculations, we show that interactions of valence electrons in the solid lead to a level broadening of the atomic ground state, which considerably suppresses the resonant scattering of neutrinos.

Summary Pollen immunotherapy exerts greater efficacy in the pollen season when the pollen count is not high than when it is high. Every pollen season, around half or more patients who have received pollen immunotherapy for >5 years are judged as good responders; those who have received immunotherapy for 1000 U/mL). The incidence of systemic reactions in patients with 1 risk factor such as asthma, atopic dermatitis, and high IgE was 16.9%/patient and 0.1%/injection, whereas that in those without risk factors was 1.6%/patient and

Summary The possible cure of Japanese cedar pollen-induced allergic rhinitis (AR) by immunotherapy was investigated. The mechanism of cure was also studied from the viewpoint of the T cell response to allergen; it was documented that absence of IL-5 production from allergen-stimulated T cells was the major mechanism. The prophylactic aspect of immunotherapy was also investigated. Eighty-eight asymptomatic subjects who were already sensitized to pollen were recruited. Of these subjects, 31 (prophylactic immunotherapy group) were treated with pollen immunotherapy for 3 years. The remaining 57 individuals (control group) were not treated with pollen immunotherapy. At the end of the 3-year trial, only 28 of 57 individuals (49.1%) in the control group remained asymptomatic. On the other hand, 27 of 31 individuals (87.1%) in the prophylactic immunotherapy group remained asymptomatic. Prophylactic immunotherapy decreased IL-4 synthesis from pollen allergen-stimulated T cells, suggesting that this was the mechanism of prevention of symptoms' outbreak. We next examined whether mite immunotherapy for patients monosensitized to mite allergen could prevent new sensitization to pollens. A total of 132 patients monosensitized to house dust mites were included. Of these individuals, 52 (pharmacotherapy group) were treated with antihistamine tablets for 4 years, and the remaining 80 patients (mite immunotherapy group) were treated with mite immunotherapy for the same time period. Whereas 15 of 52 patients (28.8%) in the pharmacotherapy group attained new sensitization to some kinds of pollen allergens, only five of 80 patients (6.3%) in the mite immunotherapy group attained new sensitization. Our data suggest that mite immunotherapy can prevent new sensitization to pollen allergens. It is therefore concluded that pollen immunotherapy cannot only cure pollen-induced AR but also prevent outbreaks of pollen-induced AR, and that mite immunotherapy can prevent new sensitization to pollen allergens.

Gmelin larch (Larix gmelinii) forests are representative vegetation in the continuous permafrost region of Central Siberia. Information on the carbon budget is still limited for this Siberian larch taiga in comparison to boreal forests in other regions, while the larch forests are expected to play a key role in the global carbon balance due to their wide distribution over North–East Eurasia. The authors reported results of eddy covariance CO2 flux measurements at a mature Gmelin larch stand in Central Siberia, Russia (64°16′N, 100°12′E, 250 m a.s.l.). The measurements were conducted during one growing season (June-early September in 2004). CO2 uptake was initiated in early June and increased sharply until late June, which was closely related to the phenology of the larch trees (i.e., bud-break and needle flush). Maximum half-hourly net CO2 uptake was ∼6 µmol m−2 s−1. Maximum daily net uptake of ∼2 g C m−2 day−1 occurred at the end of June and in mid-July. Cumulative net uptake was 76–78 g C m−2, indicating that the mature larch forest acted as a net sink for CO2 during the growing season (91 days). In comparison with other boreal forests, however, the magnitude of net CO2 uptake and night-time release of the forest, and cumulative net CO2 uptake were lower. We suggest that lower net ecosystem CO2 uptake of the study stand was primarily associated with low leaf area index.

We studied the selective formation of Co catalyst particles as a function of indentation pressure. We subjected a Co (8 nm thickness)/Si substrate pre-annealed at 600 °C to indentation processing. The catalytic function was confirmed in the indentations by the selective growth of carbon nanotubes (CNTs) at 800 °C. The number density of CNTs against the indentation pressure was investigated against indentation loads for two types of indenter: a Berkovich indenter with a ridge angle of 115° and a Berkovich indenter with a ridge angle of 90°. The pressures above 7 GPa applied by the former indenter enhanced Co atomization acting as a catalyst function for CNT growth (35 CNTs in one indentation). In contrast to this, the number of CNTs was markedly reduced when the latter indenter was used with pressures less than 3 GPa. The pop-out phenomenon was observed in unloading curves at pressures above 7 GPa. These results indicate that metastable Si promotes the self-aggregation of catalyst particles (Co) leading to the selective growth of CNTs within indentations at pressures above 7 GPa.

A laser-driven proton beam with a maximum energy of a few MeV is stably obtained using an ultra-short and high-intensity Ti:sapphire laser. At the same time, keV X-ray is also generated at almost the same place where protons are emitted. Here, we show the successful demonstration of simultaneous proton and X-ray projection images of a test sample placed close to the source with a resolution of ~10 µm, which is determined from the source sizes. Although the experimental configuration is very simple, the simultaneity is better than a few hundreds of ps. A CR-39 track detector and imaging plate, which are placed as close as possible to the CR-39, are used as detectors of protons and X-ray. The technique is applicable to the precise observation of microstructures.