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Background: Parenteral nutrition (PN) without enteral nutrition (EN) leads to marked atrophy of gut-associated lymphoid tissue (GALT), causing mucosal defense failure in both the gut and the extraintestinal mucosal system. We evaluated the effects of beta-hydroxy-beta-methylbutyrate (HMB) on GALT and gut morphology in PN-fed mice., Methods: Experiment 1: male Institute of Cancer Research mice were assigned to the Chow (n = 12), Control (standard PN: n = 10), or H600 and H2000 (PN containing 600 mg/kg or H2000 mg/kg body weight of Ca-HMB: n = 12 and 10, respectively) groups. After 5 days of dietary manipulation, all mice were killed and the whole small intestine was harvested. GALT lymphocyte cell numbers and phenotypes of Peyer patch (PP), intraepithelial space, and lamina propria lymphocytes were evaluated. Experiment 2: 47 mice (Chow: n = 12; Control: n = 14; H600: n = 11; and H2000: n = 10) were fed for 5 days as in experiment 1. Proliferation and apoptosis of gut immune cells and mucosa, and protein expressions (mammalian target of rapamycin [mTOR], caspase-3, and Bcl2) were evaluated in the small intestine., Results: Compared with the Controls, the Chow and HMB groups showed significantly higher PP cell numbers, prevented gut mucosal atrophy, inhibited apoptosis of gut cells, and increased their proliferation in association with increased mTOR activity and Bcl2 expression., Conclusion: HMB-supplemented PN is a potentially novel method of preserving GALT mass and gut morphology in the absence of EN., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background and Aims: To overcome the technical difficulties associated with gastric endoscopic submucosal dissection (ESD), a novel traction device that can alter the direction of traction was developed. This study compared the efficacy and safety of conventional ESD versus those of traction-assisted gastric ESD., Methods: Patients with a single gastric epithelial neoplasm were randomized to receive conventional (n = 75) or traction-assisted (n = 73) gastric ESD. The primary outcome was ESD procedure time., Results: There were no differences between the conventional and traction-assisted groups with respect to treatment results or adverse events. The mean procedure time was similar for both groups (78.9 vs 88.3 minutes, respectively; P = .3); however, times for the traction device tended to be shorter for lesions in the lesser curvature of the upper or middle stomach (84.6 vs 123.2 minutes; P = .057)., Conclusions: Traction-assisted ESD for lesions in the lesser curvature of the upper or middle stomach were shorter, thereby reducing the procedure time of conventional ESD. (Clinical trial registration: University Hospital Medial Information Network Clinical Trials Registry, identifier 000044450.)., Competing Interests: Disclosure The following author disclosed financial relationships: M. Kitano: honoraria from Olympus Corporation (for delivering lectures at conferences). All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD)., Methods: The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO., Results: Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events., Conclusion: Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Plasma membrane (PM) H + -ATPase is crucial for light-induced stomatal opening and phosphorylation of a penultimate residue, Thr948 (pen-Thr, numbering according to Arabidopsis AHA1) is required for enzyme activation. In this study, a comprehensive phosphoproteomic analysis using guard cell protoplasts from Vicia faba shows that both red and blue light increase the phosphorylation of Thr881, of PM H + -ATPase. Light-induced stomatal opening and the blue light-induced increase in stomatal conductance are reduced in transgenic Arabidopsis plants expressing mutant AHA1-T881A in aha1-9, whereas the blue light-induced phosphorylation of pen-Thr is unaffected. Auxin and photosynthetically active radiation induce the phosphorylation of both Thr881 and pen-Thr in etiolated seedlings and leaves, respectively. The dephosphorylation of phosphorylated Thr881 and pen-Thr are mediated by type 2 C protein phosphatase clade D isoforms. Taken together, Thr881 phosphorylation, in addition of the pen-Thr phosphorylation, are important for PM H + -ATPase function during physiological responses, such as light-induced stomatal opening in Arabidopsis thaliana., (© 2024. The Author(s).)

Ticks are blood-sucking ectoparasites and can transmit various pathogens of medical and veterinary relevance. The life cycle of ticks can be completed under laboratory conditions on experimental animals, but the artificial feeding of ticks has attracted increased interest as an alternative method. This study represents the first report on the successful in vitro feeding of all life stages of two-host tick species, Hyalomma scupense and Hyalomma excavatum, and the three-host tick Hyalomma dromedarii. The attachment and engorgement rates of adults were 84% (21/25) and 76% (19/25) for H. scupense females. For adult H. excavatum and H. dromedarii, 70% (21/30) and 34.4% (11/32) of the females attached and all attached females successfully fed to repletion. The oviposition rates of the artificially fed females were 36.4%, 57.1% and 63.1% for H. dromedarii, H. excavatum and H. scupense, respectively, with a reproductive efficiency index varying between 44.3 and 60.7%. For the larvae, the attachment and engorgement rates were 44.2% (313/708) and 42.8% (303/708) for H. dromedarii, 70.5% (129/183) and 56.8% (104/183) for H. excavatum and 92.6% (113/122) and 55.7% (68/122) for H. scupense. The attachment and engorgement rates for the nymphs were 90.2% (129/143) and 47.6% (68/143) for H. dromedarii, 66.7% (34/51) and 41.2% (21/51) for H. excavatum, and 44.1% (30/68) and 36.8% (25/68) for H. scupense. Molting rates of the immature stages varied between 71.3% (216/303) and 100% (68/68) for the larvae and between 61.9% (13/21) and 96% (24/25) for the nymphs. The successful in vitro feeding of all stages of the three Hyalomma species makes this method a valuable tool for tick research, with potential applications in studies on the pathogens transmitted by these tick species such as Theileria annulata., (© 2024. The Author(s).)

Solid phase extraction (SPE) is a technique widely used in food analysis for the isolation of analytes. Herein, we proposed a novel application of SPE to extract vaporised propionic acid, a common preservative, from a heated sample solution. A sample was heated under acidified conditions and the resulting steam was directly passed through an SPE column to extract the propionic acid, followed by elution and HPLC analysis. Here, the extraction on the SPE column ensures direct capture of propionic acid. The results demonstrated excellent linearity (R 2  greater than 0.999) and recoveries of 89.9%-97.6% with intra- and inter-day precisions lower than 3.9%. To the best of our knowledge, no study has investigated the applicability of SPE to an analyte vaporised in the headspace of food products. The proposed method is promising in its application to various volatile compounds and in the routine analysis of propionic acid in food., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Retrospective cohort study. Spinal deformities in patients with Marfan syndrome (MFS) are distinct from those in patients with idiopathic scoliosis (IS). It is more prone to progression and more likely to present with sagittal malalignment than IS. However, the etiology of this characteristic spinal deformity in MFS remains unclear. This study aimed to determine the spinal musculature characteristics in patients with MFS on the hypothesis that the paraspinal muscles of patients with MFS would be qualitatively or quantitatively different from those of patients with IS. Seventeen consecutive patients with MFS aged 25 years or younger undergoing surgery for scoliosis in our hospital were compared with age- and sex-matched patients with IS undergoing surgery for scoliosis. The body size-adjusted relative cross-sectional area (rCSA), fatty infiltration ratio (FI%), and relative functional cross-sectional area (rFCSA) of the psoas muscles (PM) and paravertebral muscles (PVM) at L3/4 and L4/5 were measured using preoperative T2-weighted magnetic resonance imaging. Functional CSA was defined as total CSA minus the fatty infiltration area of each muscle and rFCSA was calculated as the body size-adjusted functional CSA. The rCSA of the PM at L3/4 and L4/5 was significantly smaller in the MFS group than in the IS group (L3/4, P = .021; L4/5, P = .002). The FI% of the PM at L4/5 was significantly higher in the MFS group (P = .044). Consequently, the rFCSA of the PM at L3/4 and L4/5 and the rFCSA of the PVM at L3/4 in the MFS group were significantly smaller than those in the IS group (PM at L3/4, P = .021; PM at L4/5, P = .001; PVM at L3/4, P = .025). Compared with patients with IS, patients with MFS exhibited significantly decreased body-size-adjusted CSA of the PM and reduced body-size-adjusted functional CSA of the PVM and PM. These findings may partially explain the characteristics of distinctive spinal deformities in patients with MFS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Glucose transporters (GLUTs) are highly expressed in various cancers. However, the implications of these variable expression patterns are unclear. This study aimed to clarify the correlation between class I GLUT expression patterns and clinical outcomes in non-small cell lung cancer (NSCLC), including their potential role in inflammatory signaling., Methods: Biopsy tissues from 132 patients with NSCLC (92 adenocarcinomas [ADC] and 40 squamous cell carcinomas [SQCC]) were analyzed. mRNA expression levels of class I GLUTs (solute carrier 2A [SLC2A]1, SLC2A2, SLC2A3, and SLC2A4) and inflammation-related molecules (toll-like receptors TLR4, RelA/p65, and interleukins IL8 and IL6) were measured. Cellular localization of GLUT3 and GLUT4 was investigated using immunofluorescence., Results: Single, combined, and negative GLUT (SLC2A) expression were observed in 27/92 (29.3%), 27/92 (29.3%), and 38/92 (41.3%, p < 0.001) of ADC and 8/40 (20.0%), 29/40 (72.5%, p < 0.001), and 3/40 (7.5%) of SQCC, respectively. In ADC, the single SLC2A3-expressed group had a significantly poorer prognosis, whereas the single SLC2A4-expressed group had a significantly better prognosis. The combined expression groups showed no significant difference. SLC2A expression was not correlated with SQCC prognosis. SLC2A4 expression correlated with lower IL8 expression. GLUT3 and GLUT4 expressions were localized in the tumor cytoplasm., Conclusions: In lung ADC, single SLC2A3 expression correlated with poor prognosis, whereas single SLC2A4 expression correlated with better prognosis and lower IL8 expression. GLUT3 expression, which is increased by IL8 overexpression, may be suppressed by increasing the expression of GLUT4 through decreased IL8 expression., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

An Arabidopsis mutant displaying impaired stomatal responses to CO 2 , cdi4, was isolated by a leaf thermal imaging screening. The mutated gene PECT1 encodes CTP:phosphorylethanolamine cytidylyltransferase. The cdi4 exhibited a decrease in phosphatidylethanolamine levels and a defect in light-induced stomatal opening as well as low-CO 2 -induced stomatal opening. We created RNAi lines in which PECT1 was specifically repressed in guard cells. These lines are impaired in their stomatal responses to low-CO 2 concentrations or light. Fungal toxin fusicoccin (FC) promotes stomatal opening by activating plasma membrane H + -ATPases in guard cells via phosphorylation. Arabidopsis H + -ATPase1 (AHA1) has been reported to be highly expressed in guard cells, and its activation by FC induces stomatal opening. The cdi4 and PECT1 RNAi lines displayed a reduced stomatal opening response to FC. However, similar to in the wild-type, cdi4 maintained normal levels of phosphorylation and activation of the stomatal H + -ATPases after FC treatment. Furthermore, the cdi4 displayed normal localization of GFP-AHA1 fusion protein and normal levels of AHA1 transcripts. Based on these results, we discuss how PECT1 could regulate CO 2 - and light-induced stomatal movements in guard cells in a manner that is independent and downstream of the activation of H + -ATPases. [Correction added on 15 May 2023, after first online publication: The third sentence is revised in this version.]., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Introduction: Endoscopic submucosal dissection (ESD) allows the en bloc resection of colorectal epithelial tumors regardless of size. Although ESD is minimally invasive and yields favorable outcomes, it is technically difficult and requires a long procedure time. In addition, colorectal ESD is associated with a particularly high risk of complications, due to the thin bowel wall, bowel flexion, and peristalsis.Direct visualization of the submucosal layer by traction of the lesion after mucosal dissection would make ESD performance easier. S-O clips traction lesions toward the lumen, facilitating direct visualization of the submucosal layer, resulting in efficient dissection due to the traction effect and adequate dissection depth. Use of this traction device can contribute to shortening the procedure time and reducing the risk of complications. This multicenter randomized controlled trial will evaluate the usefulness of the S-O clip in colorectal ESD and assess the procedure time and frequency of complications associated with the procedure., Methods/design: This multicenter, randomized control trial will enroll 200 patients at 4 hospitals in Japan undergoing ESD for colorectal epithelial tumors. Patients who meet the inclusion and exclusion criteria will be randomized to undergo ESD using S-O clips or conventional ESD. Patients will be randomized by a computer-generated random sequence with stratification by operator experience (trainee or expert), tumor location (colon/rectum), and institution. The primary endpoint will be ESD procedure time, defined as the time from the start of the local injection into the submucosal layer to the end of dissection. Other outcomes will include the rates of procedural complications, en bloc resection and cure., Discussion: ESD using the S-O clip is expected to shorten procedure time, reduce the incidence of adverse events, and standardize the procedure. This study may resolve clinical questions about whether ESD using the S-O clip traction device is more effective and safer than conventional ESD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: We previously demonstrated that prehabilitation by running on a treadmill leads to improved survival after gut ischemia reperfusion (I/R) in mice. The purpose of this research was to examine whether prehabilitation attenuates inflammatory responses after gut I/R in mice., Materials and Methods: Male C57BL/6J mice (n = 92) were assigned to the sedentary (n = 46) or the exercise (n = 46) group. The exercise group ran on a treadmill for 4 wk, while the sedentary mice did not exercise. After the 4-week pretreatment, all mice underwent gut I/R and the blood, urine, small intestine, lung, liver, and gastrocnemius were harvested prior to ischemia or at 0, 3, 6, or 24 h after reperfusion. Histologically demonstrated organ damage, cytokine levels in the blood, gut and gastrocnemius, myeloperoxidase activity in the gut, 8-hydroxy-2'-deoxyguanosine levels in urine and the gut, and adenosine triphosphate (ATP) and ATP + ADP + adenosine monophosphate levels in the gut and gastrocnemius were evaluated., Results: The treadmill exercise reduced gut and lung injuries at 3 h and liver injury at 6 h after reperfusion. Running on the treadmill also decreased proinflammatory cytokine levels in the blood at 6 h, gut at 3 h and gastrocnemius at 6 h after reperfusion, myeloperoxidase activity in the gut prior to ischemia, and 6 h after reperfusion and the urinary 8-hydroxy-2'-deoxyguanosine level at 24 h after reperfusion, while ATP levels in exercised mice prior to ischemia and 3 h after reperfusion were increased in the intestine as compared to the levels in sedentary mice., Conclusions: Prehabilitation with treadmill exercise reduces inflammatory responses after gut I/R and may exert protective actions against gut I/R., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ets1 deletion in some mouse strains causes septal defects and has been implicated in human congenital heart defects in Jacobsen syndrome, in which one copy of the Ets1 gene is missing. Here, we demonstrate that loss of Ets1 in mice results in a decrease in neural crest (NC) cells migrating into the proximal outflow tract cushions during early heart development, with subsequent malalignment of the cushions relative to the muscular ventricular septum, resembling double outlet right ventricle (DORV) defects in humans. Consistent with this, we find that cultured cardiac NC cells from Ets1 mutant mice or derived from iPS cells from Jacobsen patients exhibit decreased migration speed and impaired cell-to-cell interactions. Together, our studies demonstrate a critical role for ETS1 for cell migration in cardiac NC cells that are required for proper formation of the proximal outflow tracts. These data provide further insights into the molecular and cellular basis for development of the outflow tracts, and how perturbation of NC cells can lead to DORV., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Light induces stomatal opening, which is driven by plasma membrane (PM) H + -ATPase in guard cells. The activation of guard-cell PM H + -ATPase is mediated by phosphorylation of the penultimate C-terminal residue, threonine. The phosphorylation is induced by photosynthesis as well as blue light photoreceptor phototropin. Here, we investigated the effects of cessation of photosynthesis on the phosphorylation level of guard-cell PM H + -ATPase in Arabidopsis thaliana. Immunodetection of guard-cell PM H + -ATPase, time-resolved leaf gas-exchange analyses and stomatal aperture measurements were carried out. We found that light-dark transition of leaves induced dephosphorylation of the penultimate residue at 1 min post-transition. Gas-exchange analyses confirmed that the dephosphorylation is accompanied by an increase in the intercellular CO 2 concentration, caused by the cessation of photosynthetic CO 2 fixation. We discovered that CO 2 induces guard-cell PM H + -ATPase dephosphorylation as well as stomatal closure. Interestingly, reverse-genetic analyses using guard-cell CO 2 signal transduction mutants suggested that the dephosphorylation is mediated by a mechanism distinct from the established CO 2 signalling pathway. Moreover, type 2C protein phosphatases D6 and D9 were required for the dephosphorylation and promoted stomatal closure upon the light-dark transition. Our results indicate that CO 2 -mediated dephosphorylation of guard-cell PM H + -ATPase underlies stomatal closure., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Introduction: Although parenteral nutrition (PN) is the only option for providing adequate nutrition to patients who cannot tolerate oral ingestion, it severely impairs intestinal barrier function in terms of morphology and immunity. While addition of either soybean oil (SO) or fish oil (FO) to PN partially reverses these defects, the effects of the oil composition (FO/SO ratio) on morphology and gut-associated lymphoid tissues (GALT) have yet to be elucidated. We focused on the effects of the FO/SO ratio in PN on the number of lymphocytes in Peyer's patches, immunoglobulin A levels, and intestinal structures., Methods: Male ICR mice (n = 61) were randomized into five groups; oral nutrition (Chow, n = 14) and four groups receiving PN without oral nutrition. PN solutions contained fat emulsions with the following FO:SO ratios: 0:1 (SO, n = 12), 1:11.5 (11.5FSO, n = 17),1:2 (1:2FSO, n = 13) and 1:0 (FO, n = 5). All mice underwent jugular vein catheter insertion. The PN groups were given isocaloric and isonitrogenous nutritional support with 20% of total calories from fat emulsions with equivalent fat delivery in 11.9 g/kg/d. After 5 d of each feeding, Peyer's patches lymphocytes were isolated from the small intestine, counted and analyzed with flowcytometry for determination of their phenotypes (αβTCR+, γδTCR+, CD4+, CD8+ and B cells). Villus height and crypt depth of the jejunum and ileum were evaluated with hematoxylin-eosin staining. Immunoglobulin A levels in the intestinal washings were also determined., Results: Numbers of total lymphocytes and B lymphocytes in PP were increased in the 1:2 FSO-PN but neither in the 1:11.5 FSO nor the FO group, as compared to the SO group. There were no marked differences among the groups in numbers neither of total T cells nor in any of T cell phenotypes determined. The 1:2 FSO group showed significantly greater villus height and crypt depth than the SO group. IgA levels did not differ significantly among the four PN groups., Conclusions: The PN with 1:2 FSO (FO:SO = 1:2) maintained lymphocyte numbers in PP and intestinal villus morphology at levels nearly the same as those obtained with chow feeding. An appropriate ratio of FO to SO in PN is expected to prevent immunological impairment and morphological atrophy of the gut associated with lack of oral nutrition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: We developed the world's first all-in-one type peripheral parenteral nutrition product containing dextrose, amino acids, fat emulsion, electrolytes and vitamins, according to the FDA 2000 recommendation. This phase I trial examined the safety and changes in nutritional parameters in healthy participants., Methods: A single-center, randomized, open-label, active-controlled trial was performed in single ascending dose (SAD: Step 1-3) and multiple dose (Step 4) studies. Participants were administered a single dose of OPF-105 (test solution: 150 g of dextrose, 60 g of amino acids, 40 g of fat, 1240 kcal of total energy per 2200 mL, and 106 NPC/N ratio, with multivitamins, n = 17) or BFI (control solution: 150 g of dextrose, 60 g of amino acids, 840 kcal of total energy per 2000 mL, and 64 NPC/N ratio, with vitamin B1, n = 18) with three ascending doses (Step 1: 550 mL, Step 2: 1100 mL, and Step 3: 2200 mL) in the SAD study, or received multiple doses with Step 3 amount of OPF-105 (n = 5) or BFI (n = 6) for 3 days (Step 4) via peripherally inserted venous catheters. The safety and nutritional parameters were assessed., Results: There were no serious adverse events or events requiring discontinuation of the solution administration in either group. Blood urea nitrogen (BUN) levels remained within the normal range in both groups (Step 1-4). However, they gradually increased during the time course of the study in the BFI group but not in the OPF group (Step 4), suggesting the prevention of body protein breakdown. Blood triglyceride (TG) levels increased after administration in the OPF group but promptly returned to the pre-administration level (Step 1-4). Blood total ketone body levels increased the day after administration in both groups, which may imply a lower degree of starvation (Step 1-3), but the increase in the OPF group was milder than that in the BFI group (Step 4). Blood vitamin B6 and folic acid levels were maintained within the normal ranges in the OPF group but were near the lower limit in the BFI group (Step 1-4). Blood vitamin C levels showed almost lower limit in the two groups (Step 1-3), but increased only in the OPF group (Step 4). Blood vitamin K levels in the BFI group remained near the lower limit of the normal range, but those in the OPF group were higher than the upper limit at the end of administration and quickly returned to the pre-administration level (Step 1-4)., Conclusions: This trial suggests that the newly developed formula (OPF-105) improves fat metabolism, maintains vitamin profiles, and may prevent body protein and fat breakdown and can be safely administered to healthy participants. Registration number of Clinical Trial: UMIN000046915; https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000053479., Competing Interests: Declaration of competing interest Kazuhiko Fukatsu and Ryuzaburo Shineha received payments from Otsuka Pharmaceutical Factory, Inc., for conducting this trial and writing the manuscript. Mitsuo Nakayama, Yoshiyuki Kawauchi, and Satoshi Katayose are employees of the Otsuka Pharmaceutical Factory, Inc., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study proposes and assesses a new diffusion MRI (dMRI) technique to solve problems related to the quantification of parameter maps (apparent diffusion coefficient [ADC] or mean diffusivity [MD], fractional anisotropy [FA]) and misdrawing of fiber tractography (FT) due to cerebrospinal fluid (CSF)-partial volume effects (PVEs) for brain tissues by combining with the T2-based water suppression (T2wsup) technique., Methods: T2wsup-diffusion-weighted imaging (DWI) images were obtained by subtracting those images from the acquired multi-b value (b) DWI images after correcting the signal intensities of multiecho time (TE) images using long TE water signal-dominant images. Quantitative parameter maps and FT were obtained from minimum data points and were compared with those using the standard (without wsup) DWI method, and partly compared with those obtained using other alternative DWI methods of applying fluid attenuation inversion recovery (FLAIR), non-b-zero (NBZ) by theoretical or noise-added simulation and MR images., Results: In the T2wsup-dMRI method, the hyperintense artifacts due to CSF-PVEs in MRI data were dramatically suppressed even at lower b (≲ 500 s/mm 2 ) while keeping the tissue SNR. The quantitative parameter map values became precisely close to the pure tissue values precisely even in water (CSF) PVE voxels in healthy brain tissues (T2 ≲ 100 ms). Furthermore, the fiber tracts were correctly connected, particularly at the fornix in closest contact to the CSF., Conclusion: Solving the problem of CSF-PVE in the current dMRI technique using our proposed T2wsup-dMRI technique is easy, with higher SNR than those obtained with FLAIR or NBZ methods when applying to healthy brain tissues. The proposed T2wsup-dMRI could be useful in clinical settings, although further optimization of the pulse sequence and processing techniques and clinical assessments are required, particularly for long T2 lesions.

Increased levels of dialkylphosphates (DAP) in maternal urine are associated with a variety of adverse developmental outcomes in children. Although urinary DAP levels are usually considered to be a marker of exposure to organophosphate (OP) pesticides, excretion of DAP may also increase by ingesting preformed DAP. To date, no study has quantitatively assessed the possible contribution of the dietary intake of preformed DAP and OP pesticides to urinary levels of DAP. Therefore, we aimed to estimate the levels of 6 DAPs and 84 OP pesticides in duplicate diet samples and urine samples collected from 73 women living in urban areas of Japan in 2018. DAP and OP pesticides were detected in 94% and 45% of diet samples, while DAP was detected in 100% of urinary samples, respectively. The average daily intake of preformed DAP was significantly higher than that of parent OP pesticides in our participants. Dimethylphosphate and diethylphosphate were predominant in the preformed DAP, and the estimated average daily intake of total amount of DAP was 78.3 nmol. Fruits and vegetables were the major dietary sources of DAP. Dietary intake of DAP was positively associated with urinary DAP levels, suggesting that a considerable amount of urinary DAP was derived from ingesting preformed DAP. Our results show that attributing urinary DAP levels exclusively to OP pesticide exposure would result in a substantial overestimation of the exposure level. Therefore, the urinary levels of DAP may not be suitable for evaluating OP pesticide exposure in the general urban population., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Endoscopic submucosal dissection (ESD) is an advanced therapeutic technique for en bloc resection of superficial gastrointestinal neoplasms. Although gastric ESD is minimally invasive and provides favorable outcomes, it is technically difficult and requires a long procedure time for dissection. The traction-assisted approach overcomes some of the difficulties of gastric ESD, but its ability to reduce the procedure time remains unclear. The traction-assisted approach using dental floss and a clip did not reduce procedure time in the total population, but it reduced procedure time for lesions limited to the greater curvature of the upper or middle of the stomach. Although the traction direction of the clip-with-line method may be limited to the oral side via the cardia, EndoTrac ESD may provide flexible traction at any time during the procedure. This prospective randomized control study has been designed to compare the efficacy and safety of EndoTrac and conventional gastric ESD., Methods/design: This multicenter, randomized control trial will enroll 150 patients at 2 hospitals in Japan undergoing EndoTrac or conventional ESD for gastric epithelial neoplasia. Patients with a single gastric epithelial neoplasm who meet the inclusion and exclusion criteria will be randomized to EndoTrac or conventional ESD. Patients will be randomized by a computer-generated random sequence with stratification by operator experience, tumor size, tumor location, and institution. The primary endpoint will be ESD procedure time, defined as the time from the start of the submucosal injection to the completion of resection. Other outcomes will include the rates of adverse events and pathological curability., Discussion: The ability of EndoTrac ESD to reduce the long procedure time and/or adverse events observed with conventional ESD can not only reduce physical stress on the patient, but can also reduce length of hospital stay and medical costs. Reduced technical difficulty will contribute to the widespread adoption of this ESD technique worldwide., Trial Registration: University Hospital Medial Information Network Clinical Trials Registry (UMIN-CTR), ID: 000044450; Registered on June 6, 2021.https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000050485., Protocol Version Number: 1.1, March 1, 2022. Patient enrolment began on June 6, 2021 and is expected to be completed by July 19, 2025., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Internal quality control (IQC) is essential to ensure the reliability of the results of chemical analysis. In this study, we propose a novel method of IQC for multiresidue analysis of pesticides. A total of seven stable isotope labeled compounds (SILC) were added to analytical samples and were used to monitor and evaluate the quality of analytical results. In contrast to conventional IQC method in which only a limited number of control materials were analyzed to ensure the reliability of the results for an entire batch, the developed method can monitor the analytical quality of all the samples in the batch. It was shown that the developed method could achieve better performance than that of conventional method. Therefore, the developed method is considered to be promising for practical applications.(Received January 27, 2022; Accepted July 4, 2022).

Introduction: We assessed the efficacy and safety of OPF-105, a novel all-in-one peripheral parenteral nutrition (PPN) solution containing multivitamins by the U.S. Food and Drug Administration in 2000 (FDA2000 recommendation)., Methods: We conducted a phase III trial administering OPF-105 or BFL (combination of a commercially available PPN solution and fat emulsion) to patients after gastrointestinal (GI) tract surgery from postoperative day (POD) 1 up to POD14. Until POD7, nutrients were provided only with OPF-105 or BFL. After blood sampling on POD8, oral food intake was permitted. PPN was administered according to the amount of food intake., Results: Efficacy endpoints were assessed in 99 subjects (OPF group: 52; BFL group: 47). The levels of blood proteins and fatty acids in the two groups were similar on POD8. The transition of these mean levels was similar in both groups from POD1 or 2 to POD9 to 15. The mean preoperative blood vitamin levels were within reference intervals (RIs). On POD1 (before administration), the mean levels of most blood vitamins decreased compared to those of the preoperative levels. In the BFL group, the mean blood levels of vitamin B2, B6, pantothenic acid (PA), folic acid (FA), biotin, and C decreased below or near the lower limit of RIs on POD8, and the mean blood levels of vitamin B6 and C remained low from POD9 to 15. In the OPF group, the mean blood levels of vitamins, excluding vitamin K, were within RIs on POD8 and POD9 to 15. The mean levels of blood vitamin K increased over the upper limit of RIs on POD8 but within RIs from POD9 to 15. There was no obvious difference in the incidence of adverse events between the two groups, which is common after GI tract surgeries., Conclusion: Blood vitamin levels decreased when patients were administered PPN without vitamin supplementation during the first week after surgery. The novel PPN formula containing multivitamins recommended by FDA2000 can be safely administered to postoperative patients to maintain blood vitamin levels., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

An unknown 61 kDa protein is phosphorylated by abscisic acid (ABA)-activated protein kinase in response to ABA and binds to 14-3-3 protein in a phosphorylation-dependent manner in guard-cell protoplasts (GCPs) from Vicia faba . Subsequently, ABA-dependent phosphorylated proteins were identified as basic helix-loop-helix transcription factors, named ABA-responsive kinase substrates (AKSs) in GCPs from Arabidopsis thaliana . However, whether the 61 kDa protein in Vicia GCPs is an AKS is unclear. We performed immunoprecipitation of ABA-treated Vicia GCPs using anti-14-3-3 protein antibodies and identified several AKS isoforms in V. faba (VfAKSs) by mass spectrometry. The 61 kDa protein was identified as VfAKS1. Phosphoproteomic analysis revealed that VfAKSs are phosphorylated at Ser residues, which are important for 14-3-3 protein binding and monomerisation, in response to ABA in GCPs. Orthologs of AtABCG40, an ABA importer in guard cells, and CHC1, a clathrin heavy chain and a regulator of stomatal movement, also co-immunoprecipitated with 14-3-3 protein from guard cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hayashi, Takahashi, Fukatsu, Tada, Takahashi, Kuwata, Suzuki and Kinoshita.)

Purpose: Our purpose was to assess our proposed new synthetic MRI (synMRI) technique, combined with T 2 -based water suppression (T 2 wsup), to reduce cerebral spinal fluid (CSF)-partial volume effects (PVEs). These PVEs are problematic in the T 2 -weighted fluid-attenuation inversion recovery (FLAIR) images obtained by conventional synMRI techniques., Methods: Our T 2 wsup was achieved by subtracting additionally acquired long TE spin echo (SE) images of water signals dominant from the originally acquired images after T 2 decay correction and a masking on the long TE image using the water volume (V w ) map to preserve tissue SNR, followed by quantitative mapping and then calculation of the synthetic images. A simulation study based on a two-compartment model including tissue and water in a voxel and a volunteer MR study were performed to assess our proposed method. Parameters of long TE and a threshold value in the masking were assessed and optimized experimentally. Quantitative parameter maps of standard and with T 2 wsup were generated, then wsup-synthetic FLAIR and SE images were calculated using those suitable combinations and compared., Results: Our simulation clarified that the CSF-PVE artifacts in the standard synthetic FLAIR increase T 2 as the water volume increases in a voxel, and the volunteer MR brain study demonstrated that the hyperintense artifacts on synthetic images were reduced to <10% of V w in those with the standard synMRI while keeping the tissue SNR by selecting optimal masking parameters on additional long TE images of TE = 300 ms. In addition, the wsup-synthetic SE provided better gray-white matter contrasts compared with the wsup-synthetic FLAIR while keeping CSF suppression., Conclusion: Our proposed T 2 wsup-synMRI technique makes it easy to reduce the CSF-PVE artifacts problematic in the synthetic FLAIR images using the current synMRI technique by adding long TE images and simple processing. Although further optimizations in data acquisition and processing techniques are required before actual clinical use, we expect our technique to become clinically useful.

Stomatal guard cells (GCs) are highly specialized cells that respond to various stimuli, such as blue light (BL) and abscisic acid, for the regulation of stomatal aperture. Many signaling components that are involved in the stomatal movement are preferentially expressed in GCs. In this study, we identified four new such genes in addition to an aluminum-activated malate transporter, ALMT6 , and GDSL lipase, Occlusion of Stomatal Pore 1 ( OSP1 ), based on the expression analysis using public resources, reverse transcription PCR, and promoter-driven β-glucuronidase assays. Some null mutants of GC-specific genes evidenced altered stomatal movement. We further investigated the role played by ALMT6, a vacuolar malate channel, in stomatal opening. Epidermal strips from an ALMT6- null mutant exhibited defective stomatal opening induced by BL and fusicoccin, a strong plasma membrane H + -ATPase activator. The deficiency was enhanced when the assay buffer [Cl - ] was low, suggesting that malate and/or Cl - facilitate efficient opening. The results indicate that the GC-specific genes are frequently involved in stomatal movement. Further detailed analyses of the hitherto uncharacterized GC-specific genes will provide new insights into stomatal regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ye, Koya, Hayashi, Jiang, Oishi, Kato, Fukatsu and Kinoshita.)

Background: Low-carbohydrate high-fat diets (LCHFDs) are thought to be beneficial for metabolic support in patients with advanced cancer. However, whether LCHFDs affect the progression of carcinomatous peritonitis (CP) remains unclear. Our study examined the influence of a lard-based LCHFD on host immunity and survival in a murine CP model., Methods: Mice were fed either a normal diet (ND) or an LCHFD ad libitum. On day 7, Panc02 cancer cells were inoculated intraperitoneally. Mice were killed on days 7, 21, and 35, and cytokine levels in the peritoneal fluid, as well as the number and phenotypes of peritoneal, splenic, and tumor-infiltrating lymphocytes were measured. Survival studies were performed with both ad libitum and isocaloric feeding in other sets of mice., Results: The levels of all cytokines significantly increased in the LCHFD group compared with those in the ND group on day 21. The tumor necrosis factor α and interleukin-10 levels were higher in the LCHFD group than in the ND group on day 35. In the LCHFD group, the regulatory T-cell (Treg) number was significantly higher in the peritoneal cavity and tumor. The survival times were worse in the LCHFD group than in the ND group., Conclusion: The ad libitum, lard-based LCHFD feeding of CP mice increases the peritoneal cytokine levels, which may reduce splenic, anticancer lymphocytes and increase the number of Tregs in the peritoneal cavity and tumor. The detrimental effects of LCHFD are linked to dietary composition rather than overfeeding., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Benzpyrimoxan (5-(1,3-dioxan-2-yl)-4-{[4-(trifluoromethyl)phenyl]methoxy}pyrimidine, NNI-1501) was discovered as a novel insecticide structurally characterized by a pyrimidine derivative substituted with 1,3-dioxanyl and 4-trifluoromethylbenzyloxy groups. The compound showed remarkable activity against nymphs of rice planthoppers, including strains resistant to existing insecticides. Furthermore, benzpyrimoxan had low adverse effects on pollinators and beneficial arthropods. Because of these features, benzpyrimoxan is expected to be a suitable part of an integrated pest management strategy. In this report, the history of the discovery to reach benzpyrimoxan and details of the structure-activity relationships are described., (© Pesticide Science Society of Japan 2021. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: Refeeding hypophosphatemia (RH) is a potentially fatal complication in patients with anorexia nervosa (AN), and its dietary preventive strategy is not well established. We aimed to examine the association between carbohydrate content in the diet and the occurrence of RH in inpatients with AN via retrospective medical chart review., Method: We performed a chart review to collect data of patients with AN hospitalized at the Department of Psychosomatic Medicine of the University of Tokyo Hospital between April 1, 2012, and February 29, 2020. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point of the percentage of carbohydrate content in the diet for the occurrence of RH. Multivariate logistic regression analysis was performed with occurrence of RH as the dependent variable and the carbohydrate content of more than the identified cutoff point as the independent variable adjusting for the risk factors for RH., Results: The percentage of carbohydrate content that is higher than the cutoff point obtained from the ROC analysis (58.4%) was significantly associated with the occurrence of RH, even after adjusting for variables associated with RH in univariate logistic regression analysis (age and body mass index) as well as the average daily calorie intake (odds ratio, 5.37; 95% confidence interval, 1.60-18.1; p = .0066)., Discussion: We identified that diets with higher carbohydrate contents were associated with RH in inpatients with AN, even after adjusting for known risk factors. Our findings may promote the development of dietary preventive strategies against RH in inpatients with AN., (© 2020 Wiley Periodicals LLC.)

The accuracy of urine analyzers used for dogs and cats has remained uncertain. This study examines the agreement between results of urine analysis obtained using two devices marketed for animals and for humans and the results of quantitative biochemical analysis. The degrees of concordance for bilirubin and ketones in the same category were ~80%, but for pH these were only ~60% in dogs and cats. Degrees of concordance for protein and the UP/C ratio clearly differed between the devices for animals and humans. We found that values for bilirubin and ketones obtained using urine analyzers may be reliable, but pH is unlikely to be accurate enough to be clinically useful for dogs and cats.

Background: This prospective study measured body composition based on bioelectrical impedance analysis (BIA) in relation to preoperative and postoperative nutritional support and status in patients undergoing liver surgery., Methods: Thirty-seven patients with impaired liver function (indocyanine green retention rate at 15 min >15%) undergoing hepatectomy for hepatocellular carcinoma or colorectal liver metastasis were enrolled. The control group ( n = 10) received no nutritional supplementation. The late-evening snack (LES, n = 26) group received a 210-kcal snack comprising a carbohydrate with branched-chain amino acids for 2 weeks before surgery through to 12 weeks after surgery. BIA of body composition, including body cell mass and skeletal muscle volume, was performed., Results: Although there was no sarcopenia based on the consensus report of the Asian Working Group 2 weeks before surgery, the skeletal muscle volumes in the control and LES groups were at the lower limit of the normal range. Body cell mass and skeletal muscle volume were significantly lower in the control group than in the LES group at 4 ( p = 0.03) and 12 ( p = 0.02) weeks after surgery., Conclusion: Late-evening carbohydrate and branched-chain amino acid snack supplementation may improve nutritional status in patients with impaired liver function undergoing hepatectomy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 by S. Karger AG, Basel.)

Background: Preoperative carbohydrate (CHO) supplementation has been recommended in enhanced recovery after surgery protocols. However, the effects of CHO supplementation on gut and systemic immunity are not well understood., Methods: Mice (n = 60) were randomized to 1 of the following 5 groups: control (ad lib feeding), 12-hour fasting without CHO administration (fasting), and 12 hours of fasting with CHO administration at 2, 4, and 8 hours before sacrifice. Then, lymphocytes were isolated from gut-associated lymphoid tissue, that is, Peyer's patches, the intraepithelial space, and the lamina propria of the small intestine. These lymphocyte numbers and phenotypes were evaluated. IgA levels in respiratory and small-intestinal washings were determined by ELISA. Morphology, proliferation, and apoptosis of the intestinal epithelium were also evaluated histologically., Results: Although there were no significant differences in IgA levels among the 5 groups, fasting decreased intraepithelial and lamina propria, but not Peyer's patches lymphocyte numbers. CHO at 2 hours prevented lymphocyte loss in intraepithelial, whereas CHO at 4 hours reversed lamina propria lymphocytes numbers. Percentages of lymphocyte phenotypes were similar in each site among the 5 groups. Fasting caused villous atrophy; however, CHO at 2 hours restored villous structure along with maintenance of epithelial cell proliferation rate., Conclusions: Only 12 hours of fasting causes marked gut-associated lymphoid tissue cell loss along with gut atrophy. However, CHO at 2 hours preserves gut immunity and morphology not completely but moderately., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Nutrition plays important roles in recovery after gastroenterological surgery. Severe surgical stress increases muscle breakdown and lipolysis, thereby accelerating wound healing and enhancing host defense against microbes. Malnourished patients have insufficient amounts of muscle and body fat. Therefore, they may not appropriately respond to surgical stress. Perioperative nutritional therapy maintaining nutritional status reduces postoperative complications and accelerates recovery after surgery, particularly for malnourished patients. In addition, perioperative oral or enteral nutrition is now recommended for preserving host defense mechanisms against microbes. Lack of enteral nutrition impairs gut and hepatic immunity, systemic mucosal defense and peritoneal host defense, even when nutrient amounts supplied by parenteral nutrition are adequate. Thus, surgeons should avoid no oral or enteral nutrition periods. Supplemental administration of specific nutrients such as glutamine, arginine and ω-3 fatty acids is termed "immunonutrition", and is expected to reduce the morbidity of infectious complications and length of hospital stay. Nutritional therapy is important even after discharge to maintain body weight and compensate for abnormalities in the digestion and absorption of nutrients. Understanding the significance of nutrition in gastroenterological patients leads to better outcomes.

Introduction: Though micronutrient formulations for parenteral nutrition (PN) have been revised, the impacts of these changes on nutritional parameters, blood micronutrient levels, and safety have yet to be clarified. We examined the efficacy and safety of a new PN formulation with a micronutrient composition based on the Food and Drug Administration 2000 recommendation in surgical patients., Methods: This phase III clinical trial (JapicCTI-No. 142610) was a prospective, randomized, controlled, parallel-group, open-label, multicenter study. Two types of PN, OPF-108 (revised formula, n = 51) and ELN (previous formula mainly based on American Medical Association 1975 guidelines, n = 59), were given to patients from POD1 or 2 to POD7 after surgery. OPF-108 contains more vitamin B1, B6, C, and folic acid, a much lower dose of vitamin K, and less iron than ELN. Nutritional parameters and micronutrient profiles in blood and safety were evaluated., Results: Nutritional parameters on POD5 and 8 were similar between the 2 groups. Blood vitamin B1, B6, and folic acid levels on POD 5 and 8 were higher in the OPF-108 group than in the ELN group. Only OPF-108 restored vitamin C levels to within the normal range on POD5 and 8. Vitamin K levels far exceeded the upper limit of the standard range on POD5 and 8 in the ELN group, whereas OPF-108 essentially maintained these levels within the standard ranges. Serum iron levels on POD8 were nearly normal in both the OPF-108 and ELN groups., Conclusion: Beneficial effects of the new micronutrient formulation were demonstrated in surgical patients., (© 2019 S. Karger AG, Basel.)

Regulation of stomatal aperture is essential for plant growth and survival in response to environmental stimuli. Opening of stomata induces uptake of CO2 for photosynthesis and transpiration, which enhances uptake of nutrients from roots. Light is the most important stimulus for stomatal opening. Under drought stress, the plant hormone ABA induces stomatal closure to prevent water loss. However, the molecular mechanisms of stomatal movements are not fully understood. In this study, we screened chemical libraries to identify compounds that affect stomatal movements in Commelina benghalensis and characterize the underlying molecular mechanisms. We identified nine stomatal closing compounds (SCL1-SCL9) that suppress light-induced stomatal opening by >50%, and two compounds (temsirolimus and CP-100356) that induce stomatal opening in the dark. Further investigations revealed that SCL1 and SCL2 had no effect on autophosphorylation of phototropin or the activity of the inward-rectifying plasma membrane (PM) K+ channel, KAT1, but suppressed blue light-induced phosphorylation of the penultimate residue, threonine, in PM H+-ATPase, which is a key enzyme for stomatal opening. SCL1 and SCL2 had no effect on ABA-dependent responses, including seed germination and expression of ABA-induced genes. These results suggest that SCL1 and SCL2 suppress light-induced stomatal opening at least in part by inhibiting blue light-induced activation of PM H+-ATPase, but not by the ABA signaling pathway. Interestingly, spraying leaves onto dicot and monocot plants with SCL1 suppressed wilting of leaves, indicating that inhibition of stomatal opening by these compounds confers tolerance to drought stress in plants.

Background: Enteral nutrition (EN) is the gold standard of nutritional therapy for critically ill or severely injured patients, because EN promotes gut and hepatic immunity, thereby preventing infectious complications as compared with parenteral nutrition. However, there are many EN formulas with different protein and fat contents. Their effects on gut-associated lymphoid tissue remain unclear. Recently, semielemental diets (SEDs) containing whey peptides as a nitrogen source have been found to be beneficial in patients with malabsorption or pancreatitis. Herein, we examined the influences of various dietary formulations on gut immunity to clarify the advantages of SEDs over elemental diets., Methods: Forty-four male Institute of Cancer Research mice were randomized to four groups: chow (CH: n = 5), intragastric total parenteral nutrition (IG-TPN: n = 13), elemental diet (ED: n = 13), and SED (n = 13). The CH group received CH diet ad libitum, whereas the IG-TPN, ED (Elental, Ajinomoto, Japan), and SED (Peptino, Terumo, Japan) groups were given their respective diets for 5 day via gastrostomy. After 5 days, the mice were killed to obtain whole small intestines. Peyer's patch (PP) lymphocytes were harvested and counted. Their subpopulations were evaluated by flow cytometry. Immunoglobulin A (IgA) levels in intestinal and respiratory tract washings were measured with enzyme-linked immunosorbent assay. Villous height (VH) and crypt depth in the distal intestine were measured by light microscopy., Results: SED increased the PP cell number and intestinal or respiratory IgA levels to those of CH mice, while ED partially restored these parameters. The IG-TPN group showed the lowest PP cell number and IgA levels among the four groups. VH was significantly greater in the CH than in the other groups. VH in the ED and SED groups also exceeded in the IG-TPN group, while being similar in these two groups. No significant crypt depth differences were observed among the four groups., Conclusions: SED administration can be recommended for patients unable tolerate complex enteral diets or a normal diet in terms of not only absorption and tolerability but also maintenance of gut immunity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Aim: Oral administration of cystine and theanine (CT) may modulate antioxidant glutathione (GSH) metabolism, thereby improving outcomes after gut ischemia reperfusion., Methods: Experiment 1: Institute of Cancer Research mice (n = 35) were assigned to a Vehicle (n = 11), a CT140 (n = 14), or a CT280 (n = 10) group. The CT140 and 280 groups were given CT at respective dosages of 140 and 280 mg/kg (cystine: theanine = 5: 2) once daily via gavage for 5 days. All mice underwent 75-min occlusion of the superior mesenteric artery (SMA). Survival after reperfusion was observed. Experiment 2: Mice (n = 67) were pretreated for 5 days (Vehicle: n = 24, CT280: n = 20, vehicle/sham: n = 23). The Vehicle and CT280 groups underwent 60-min SMA occlusion. Levels of GSH, the oxidized form of GSH, Glutathione-S-S-Glutathione (GSSG), and GSH-related amino acids (cysteine and glutamic acid) in the small intestine, and plasma cytokine (IL-6, IL-1β, TNFα) levels, were evaluated before (0 h), 3, 6, or 9 h after reperfusion., Results: Experiment 1: The CT280 group showed significantly better survival than the Vehicle group. Experiment 2: Gut GSSG, cysteine, and glutamic acid levels were higher in the CT280 than in the Vehicle group after reperfusion. Plasma IL-6 and TNFα levels rose more rapidly in the CT280 than in the Vehicle group., Conclusion: Oral administration of CT improves survival after gut I/R, possibly through the modulation of the GSH-redox cycle and cytokine responses., (© 2018 S. Karger AG, Basel.)

It has been demonstrated that an immune-modulating enteral formula enriched with whey peptides and fermented milk (IMF) had anti-inflammatory effects in some experimental models when it was administered before the induction of inflammation. Here, we investigated the anti-inflammatory effects of the IMF administration after the onset of systemic inflammation and investigated whether the IMF could improve the remote organ injuries in an acute pancreatitis (AP) model. Mice were fasted for 12 hours and then fed a choline-deficient and ethionine-supplemented diet (CDE diet) for 24 hours to induce pancreatitis. In experiment 1, the diet was replaced with a control enteral formula, and mice were sacrificed at 24-hour intervals for 96 hours. In experiment 2, mice were randomized into control and IMF groups and received the control formula or the IMF respectively for 72 hr or 96 hr. In experiment 1, pancreatitis was induced by the CDE diet, and inflammatory mediators were elevated for several days. Remote organ injuries such as splenomegaly, hepatomegaly, and elevation of the hepatic enzymes developed. A significant strong positive correlation was observed between plasma MCP-1 and hepatic enzymes. In experiment 2, the IMF significantly improved splenomegaly, hepatomegaly, and the elevation of hepatic enzymes. Plasma MCP-1 levels were significantly lower in the IMF group than in the control group. Nutrition management with the IMF may be useful for alleviating remote organ injuries after AP.

Purpose: A study was conducted to clarify the actual status of nutrition management after gastric cancer surgery in Japan and obtain basic data for optimizing perioperative nutrition management., Methods: A questionnaire was sent to 354 hospitals with at least 50 cases of gastric cancer surgery per year. Questions included the perioperative nutrition management and length of hospital stay for patients who underwent gastric cancer surgery within three months of the survey., Results: Responses were obtained from 242 hospitals (68%; 20,858 patients). Nutrition management was consistent between laparotomy and laparoscopic surgery for 84% of respondents. The number of postoperative days was the most commonly chosen index for starting oral feeding. The most commonly chosen index for hospital dischargeability was diet composition/amount consumed in 182 hospitals (44%), followed by laboratory data stabilization in 106 hospitals (26%), and the number of postoperative days in 87 hospitals (21%). A positive correlation was found between the mean length of postoperative hospital stay and starting oral feeding (r = 0.23 for distal gastrectomy; r = 0.34 for total gastrectomy). The length of hospital stay tended to be shorter with an earlier start of oral feeding (p < 0.01)., Conclusion: Early postoperative oral feeding may be a factor in reducing the length of hospital stay after gastric cancer surgery.

The present study aimed to elucidate the association between post-vascular-phase (Kupffer-phase) images from contrast-enhanced ultrasonography (CEUS) with perfluorobutane microbubbles and metastatic recurrences after the resection of hepatocellular carcinoma (HCC). The study examined 73 patients with solitary HCC ≤5 cm in diameter who underwent CEUS before resection. HCC was defined as irregular type (including an irregular defect on Kupffer-phase images) or non-irregular type. Intrahepatic metastatic recurrence was defined as >3 intrahepatic recurrences. Metastatic recurrence included both extrahepatic and intrahepatic recurrences. Frequencies of microscopic portal invasion and intrahepatic metastasis were significantly higher in the irregular group than in the non-irregular group. Cumulative 5-y metastatic recurrence rates in the irregular and non-irregular groups were 43% and 7% (p = 0.028), respectively. Multivariate analyses identified Kupffer-phase findings as a factor significantly related to metastatic recurrence. In conclusion, HCCs with an irregular defect during Kupffer-phase CEUS are characterized by more frequent microscopic vascular invasion and intrahepatic metastasis and are significantly associated with metastatic recurrence after resection., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear., Materials and Methods: Experiment 1: male Institute of Cancer Research mice (n = 22) were assigned to the I/R or the vago-I/R group. The I/R mice underwent 45-min superior mesenteric artery (SMA) occlusion. The vago-I/R mice received vagotomy before SMA occlusion. Survival was observed for 48 h.Experiment 2: mice (n = 55) were divided into four groups (Sham, vago, I/R, vago-I/R). Sham and vago groups did not undergo gut I/R. Mice were killed at 3 or 6 h after reperfusion, and cytokine levels in the plasma, jejunum, and ileum were evaluated. In addition, gut histology at 6 h was examined.Experiment 3: mice (n = 24) were divided into four groups as in Experiment 2. The small intestine was harvested at 3 h after reperfusion and the tissue was cultured ex vivo for 3 h. Cytokine levels of the culture supernatant were then measured., Results: Experiment 1: survival was significantly worse with vago-I/R than I/R.Experiment 2: along with severe gut injury, vago-I/R increased IL-6 and monocyte chemoattractant protein-1 (MCP-1) in plasma, IFN-γ in the jejunum and MCP-1 in the ileum, as compared with I/R. Significant positive correlations were noted between plasma and intestinal levels of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α).Experiment 3: MCP-1 in the jejunal culture medium was higher in the vago-I/R than in the I/R group., Conclusions: Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.

Background: Postoperative weight loss and malnutrition are major issues in gastric cancer patients. The concept of oral nutritional supplements (ONS) is gaining widespread acceptance. We investigated the effects of ONS administration on postoperative body weight loss in patients with gastric cancer who had undergone total gastrectomy or distal gastrectomy., Methods: Patients were randomized to either the treatment or the control group. In both groups, standard surgery for gastric cancer was performed. In the treatment group, intervention with ONS was performed until 12 weeks after discharge. In the control group, patients were fed the usual postoperative diet. Weight, body composition, quality of life, hematological parameters, and blood chemistry were evaluated., Results: We analyzed 113 cases (73 distal gastrectomy, 40 total gastrectomy). Weight loss in the ONS group after total gastrectomy was significantly less than that in the control group. Weight loss and skeletal muscle mass loss after distal gastrectomy did not differ significantly between the ONS and control groups., Conclusion: This study showed ONS after total gastrectomy to significantly diminish postoperative weight loss.

BACKGROUND Recently, robotic surgery has been introduced in many hospitals. The structure of robotic instruments is so complex that updating their cleaning methods is a challenge for healthcare professionals. However, there is limited information on the effectiveness of cleaning for instruments for robotic surgery. OBJECTIVE To determine the level of residual contamination of instruments for robotic surgery and to develop a method to evaluate the cleaning efficacy for complex surgical devices. METHODS Surgical instruments were collected immediately after operations and/or after in-house cleaning, and the level of residual protein was measured. Three serial measurements were performed on instruments after cleaning to determine the changes in the level of contamination and the total amount of residual protein. The study took place from September 1, 2013, through June 30, 2015, in Japan. RESULTS The amount of protein released from robotic instruments declined exponentially. The amount after in-house cleaning was 650, 550, and 530 µg/instrument in the 3 serial measurements. The overall level of residual protein in each measurement was much higher for robotic instruments than for ordinary instruments (P<.0001). CONCLUSIONS Our data demonstrated that complete removal of residual protein from surgical instruments is virtually impossible. The pattern of decline differed depending on the instrument type, which reflected the complex structure of the instruments. It might be necessary to establish a new standard for cleaning using a novel classification according to the structural complexity of instruments, especially for those for robotic surgery. Infect Control Hosp Epidemiol 2017;38:143-146.

Entecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN- α -2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN- α -2a therapy (90  μ g per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels <100 IU/mL. Hepatitis B e antigen (HBe Ag) seroconversion rate was 25% (2/8), and VR rate was 52% (12/23). CR was observed in four patients (17%). However, CR rate in baseline HBs Ag level <2000 IU/mL and HBe Ag negative patients was 50% (4/8). Univariate analysis showed that the percentage of HBs Ag level reduction at week 12 was significantly associated with VR. The area under the curve value was 0.848. Adding PEG-IFN- α -2a to entecavir has limited efficacy. The percentage reduction of HBs Ag level at week 12 may be a useful predictor for VR.

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development (p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status., (© 2016 UICC.)

We report a case of negative-pressure pulmonary edema occurring by tracheal obstruction caused by the brachiocephalic artery. The patient had deformed thorax with cerebral palsy, which deformed thorax placing the brachiocephalic artery high over the trachea, resulting in close and tight contact between the artery and trachea. Additional deformity of the thorax associated with myotonic attacks after general anesthesia might shorten the distance between the sternal notch and the vertebral body, resulting in the tracheal obstruction by the artery.

Background: Surgical patients with gastrointestinal malignancies are at increased risk for malnutrition. However, the mechanism by which dietary restriction (DR), one form of malnutrition, impairs hepatic immunity remains to be clarified. The present study was designed to examine the influence of DR on hepatic mononuclear cell (MNC) numbers, subpopulations, and cytokine productions (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ], and interleukin 10 [IL-10]) in response to lipopolysaccharide (LPS) in mice. Immunoglobulin (Ig) A levels in the gallbladder and histopathologic changes in the liver were also assessed., Material and Methods: Male Institute of Cancer Research mice were randomly assigned to three dietary groups: ad libitum (AD), mild restriction (MR), and severe restriction (SR). The AD, MR, and SR groups received daily mouse chow in amounts of 190, 133, and 76 g/kg, respectively, for 7 d. After the mice had been fed for 7 d, hepatic MNCs were isolated. Total hepatic MNCs were counted and subpopulations were determined by flow cytometry. Cytokine productions (TNF-α, IFN-γ, and IL-10) by hepatic MNCs in response to LPS were measured. Blood samples were analyzed for hepatobiliary biochemical parameters. IgA levels in gallbladder bile were measured with enzyme-linked immunosorbent assay. In addition, liver histologies were examined., Results: Hepatic MNC numbers were significantly lower in the MR and SR groups than in the AD group, with no significant difference between the MR and SR groups. The percentage of B cells was significantly lower in the SR group than in the MR and AD groups, whereas the T-cell percentage was higher in the SR group than in the MR and AD groups. The percentage of Kupffer cells was significantly lower in the SR group than in the AD group, whereas that in the MR group was midway between those in the SR and AD groups. TNF-α and IL-10 levels in hepatic MNC culture supernatants were increased LPS-dose dependently in the AD group. However, the increase was slight in the MR group and absent in the SR group. The IgA levels in gallbladder bile were significantly lower in the SR and MR groups than in the AD group. On the basis of hematoxylin and eosin staining of hepatic sections, livers from the SR group showed atrophic hepatocytes and sinusoidal dilatation, whereas these changes were absent in the AD group., Conclusions: DR decreases hepatic MNC number with subpopulation changes, reduces IgA levels in gallbladder bile, blunts cytokine production by hepatic MNCs, and induces pathologic damage in the liver, which may be an important mechanism underlying the impaired host defense associated with malnutrition., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Moloney murine leukemia virus reverse transcriptase (MMLV RT) contains fingers, palm, thumb, and connection subdomains as well as an RNase H domain. The DNA polymerase active site resides in the palm subdomain, and the RNase H active site is located in the RNase H domain. The RNase H domain contains a positively charged α-helix called the C helix (H(594)GEIYRRR(601)), that is thought to be involved in substrate recognition. In this study, we expressed three versions of the RNase H domain in Escherichia coli, the wild-type domain (WT) (residues Ile498-Leu671) and two variants that lack the regions containing the C helix (Ile593-Leu603 and Gly595-Thr605, which we called ΔC1 and ΔC2, respectively) with a strep-tag at the N-terminus and a deca-histidine tag at the C-terminus. These peptides were purified from the cells by anion-exchange, Ni(2+) affinity, and Strep-Tactin affinity column chromatography, and then the tags were removed by proteolysis. In an RNase H assay using a 25-bp RNA-DNA heteroduplex, WT, ΔC1, and ΔC2 produced RNA fragments ranging from 7 to 16 nucleotides (nt) whereas the full-length MMLV RT (Thr24-Leu671) produced 14-20-nt RNA fragments, suggesting that elimination of the fingers, palm, thumb, and connection subdomains affects the binding of the RNase H domain to the RNA-DNA heteroduplex. The activity levels of WT, ΔC1, and ΔC2 were estimated to be 1%, 0.01%, and 0.01% of full-length MMLV RT activity, indicating that the C helix is important, but not critical, for the activity of the isolated RNase H domain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: There is no established method to assess the contamination of environmental surfaces because the results change with time. We evaluated current methods for assessment of contamination of environmental surfaces in the operating room (OR)., Methods: Contamination of environmental surfaces in the OR was assessed using an adenosine triphosphate (ATP) test and bacterial culture. We collected 480 ATP test samples from 17 surfaces in 6 ORs to determine the influence of surface features, including frequency of touching and surface orientation on contamination, after completion of daily scheduled operations. Another 54 pairs of ATP and microbial samples were taken from 3 surfaces in each of the same OR except 1 to determine the time course of the results of ATP and microbial tests when ORs were not used., Results: Multivariate analysis demonstrated that the ATP results were strongly influenced by frequency of touching and orientation of environmental surfaces. The microbial counts declined over time, whereas the ATP results remained at a high level., Conclusion: The ATP test result could be used as a relatively stable trace of contamination of environmental surfaces; however, it is not a surrogate indicator of the number of viable microbes which declines over time., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)