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The advantages and disadvantages of using monoethylglycinexylidide (MEGX), the major metabolite of lidocaine, as a probe of hepatic function in liver transplantation are reviewed. A ‘real time’ test of liver function should give a measure of current hepatocellular capacity rather than reflect past damage. The hepatic metabolism of lidocaine to MEGX is the basis of a flow-dependent dynamic test of liver function. In pre-transplantation patients, data from this MEGX test support its role in assessing the risk of morbidity and mortality. In assessing the liver transplant donor, there are differences concerning its apparent usefulness and these must be resolved. In the liver transplant recipient, this MEGX test is also useful for measuring real-time hepatic metabolizing activity, and low MEGX values reflect the clinical condition of the patient. At present, however, this test has several limitations. Therefore, a comprehensive evaluation, not only by the MEGX test but also by a combination of other conventional liver function tests (biochemical parameters, etc.), or with histological evaluation, is thought to be desirable for deciding whether a liver transplantation should be carried out or not. [ABSTRACT FROM AUTHOR]

Summary Background: The aim of this study was to evaluate near-infrared spectroscopy (NIRS), combined with a treadmill-walking test, as a method of assessment of intermittent claudication (IC) in diabetic patients. Methods: Some 208 symptomatic legs in 153 consecutive patients who complained of calf IC due to atherosclerotic disease were studied with NIRS and resting ankle : brachial pressure index (ABPI). Results: There was good reproducibility of NIRS measurements. Three distinct types of IC were detected by NIRS. ABPI was significantly different between these three types in non-diabetic patients, but could not grade the severity of IC in diabetic patients. Recovery time (RT) of muscle oxygenation differentiated more accurately between severe and moderate claudication than ABPI in diabetics, although RT and ABPI had similar accuracy in non-diabetics. There was a significant correlation between RT and ABPI in non-diabetic patients and patients who had been diabetic for less than 10 years, while there was no correlation in patients who had had diabetes for over 10 years. Conclusion: Measurement of muscle oxygenation during exercise by NIRS graded the severity of IC in diabetic patients more accurately than resting ABPI. An abstract based on this paper was presented to the symposium of the 18th World Congress of the International Union of Angiology in Tokyo, Japan, September 1998. [ABSTRACT FROM AUTHOR]

The clinical relevance of Acinetobacter species, other than A. baumannii, as human pathogens has not been sufficiently assessed owing to the insufficiency of simple phenotypic clinical diagnostic laboratory tests. Infections caused by these organisms have different impacts on clinical outcome and require different treatment and management approaches. It is therefore important to correctly identify Acinetobacter species. Matrix-assisted laser desorption ionization-time of flight mass spectrometry ( MALDI- TOF MS) has been introduced to identify a wide range of microorganisms in clinical laboratories, but only a few studies have examined its utility for identifying Acinetobacter species, particularly those of the non- Acinetobacter baumannii complex. We therefore evaluated MALDI- TOF MS for identification of Acinetobacter species by comparing it with sequence analysis of rpoB using 123 isolates of Acinetobacter species from blood. Of the isolates examined, we identified 106/123 (86.2%) to species, and 16/123 (13.0%) could only be identified as acinetobacters. The identity of one isolate could not be established. Of the 106 species identified, 89/106 (84.0%) were confirmed by rpo B sequence analysis, and 17/106 (16.0%) were discordant. These data indicate correct identification of 89/123 (72.4%) isolates. Surprisingly, all blood culture isolates were identified as 13 species of Acinetobacter, and the incidence of Acinetobacter pittii was unexpectedly high (42/123; 34.1%) and exceeded that of A. baumannii (22/123; 17.9%). Although the present identification rate using MALDI- TOF MS is not acceptable for species-level identification of Acinetobacter, further expansion of the database should remedy this situation. [ABSTRACT FROM AUTHOR]

The effects of blue light emitter diode (LED) light exposure on retinal pigment epithelial cells (RPE cells) were examined to detect cellular damage or change and to clarify its mechanisms. The RPE cells were cultured and exposed by blue (470 nm) LED at 4.8 mW/cm2. The cellular viability was determined by XTT assay and cellular injury was determined by the lactate dehydrogenase activity in medium. Intracellular reactive oxygen species (ROS) generation was determined by confocal laser microscope image analysis using dihydrorhodamine 123 and lipid peroxidation was determined by 4-hydroxy-2-nonenal protein-adducts immunofluorescent staining (HNE). At 24 h after 50 J/cm2 exposures, cellular viability was significantly decreased to 74% and cellular injury was significantly increased to 365% of control. Immediately after the light exposure, ROS generation was significantly increased to 154%, 177%, and 395% of control and HNE intensity was increased to 211%, 359%, and 746% of control by 1, 10, and 50 J/cm2, respectively. These results suggest, at least in part, that oxidative stress is an early step leading to cellular damage by blue LED exposure and cellular oxidative damage would be caused by the blue light exposure at even lower dose (1, 10 J/cm2). [ABSTRACT FROM AUTHOR]

This study evaluated the effects of the commonly used hydrophilic organic solvents, acetonitrile, methanol, ethanol, 1-propanol, dimethyl sulfoxide (DMSO), N,N-dimethylformamide, polyethylene glycol and propylene glycol, on CYP3A in pooled human liver microsomes, using testosterone and midazolam as substrates. Further-more, we examined the modulation effect of organic solvents on CYP3A inhibition by ketoconazole. Testoster-one 6β-hydroxylation activity was potently inhibited in the presence of DMSO and 1-propanol in a concentration-dependent manner. Midazolam 1′-hydroxylation activity, however, was weakly inhibited only by 1% of DMSO, the highest concentration used in this study. Moreover, the potency of ketoconazole to inhibit CYP3A activities was variable, depending on the organic solvent used as a dissolving solvent for ketoconazole. Our data indicate that each organic solvent had an effect on CYP3A4 activity, evaluated by both substrates with different magnitudes. Furthermore, it was shown that the effects of organic solvents on CYP3A activity are substrate-dependent. The present study also shows that methanol had little effect on either substrate. [ABSTRACT FROM AUTHOR]

Abstract: A fully coupled hydrological–mechanical–chemical (HMC) model is developed and applied to explain enigmatic spontaneous changes in permeability that develop within a fracture in limestone under simulated in situ conditions (Water Resour Res 2004;40:W03502). The water flow-through test was concurrently monitored for water and dissolved mineral mass efflux and periodically imaged by X-ray CT to provide redundant constraints on fracture evolution by dissolution and precipitation. The resulting data, exhibiting a spontaneous switch between permeability-decreasing, and permeability-increasing, are evaluated using the HMC model. This model represents these two distinct behaviors: apertures first reduce, under presumed net dissolution, and then preferentially open as net dissolution is even more positively apparent. In the model, dissolution mechanisms within the fracture can be switched from mixed-mode (a combination of pressure dissolution and free-face dissolution) to single mode (pressure dissolution or free-face dissolution). This allows both permeability reduction as mineral mass is net removed from contacting asperities, and permeability enhancement as free-face dissolution localizes along a solution channel, to be accommodated and quantified. The model successfully replicates experimental measurements in limestone. [Copyright &y& Elsevier]

Summary Background Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. Objective To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR). Methods After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 µg/day), were randomly assigned to one of two treatments – placebo (n = 98) or montelukast 10 mg once daily ( n = 93) – for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and β-agonist use. Results After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 ± 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 ± 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 ± 28.5 L/min ( P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group. Conclusion These data suggest that montelukast reduces the need for inhaled corticosteroids... [ABSTRACT FROM AUTHOR]

Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 μm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. ⟦3H〉-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 ± 3.4 μg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation. [Copyright &y& Elsevier]

The article presents an abstract of the research paper "Inhibition of Monoamine Oxidase Activity in Rat Brain by Phenoxypropylamines." For psychiatric disorders such as depression, parkinson syndromes, the monoamine oxidase (MAO) inhibitor is a useful drug. The study included the examination of the potency of inhibition of MAO activity in rat brain.

Femorofemoral bypass is an established procedure for limb salvage and disabling claudication. However, surgical exposure of the femoral artery may result in damage leading to development of an inguinal hernia. Herein we report the first case of laparoscopic repair of bilateral inguinal hernias that developed after femorofemoral bypass. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in infants treated in a neonatal intensive care unit., Methods: We examined 318 infants with a gestational age of at least 28 weeks who were treated in a neonatal intensive care unit. We investigated the relationships between slight lateral ventricular enlargement and prenatal factors. Also, we investigated the relationships between the laterality of lateral ventricular enlargement and arm growth to verify our proposed mechanism of lateral ventricular enlargement., Results: Slight lateral ventricular enlargement was observed in 97 (30.5%) infants. Slight lateral ventricular enlargement was related to gestational age ( p  < .001), maternal anemia ( p  = .025), diabetes mellitus ( p  = .048), threatened premature labor ( p  = .027), and premature rupture of the membrane ( p  = .049). In 97 infants with ventricular enlargement, the numbers of infants with left-side dominant, equivalent, and right-side dominant laterality were 60 (61.9%), 27 (27.8%), and 10 (10.3%), respectively. Maternal anemia and diabetes mellitus were related to left-side dominant ventricular enlargement. Threatened premature labor and premature rupture of the membrane were related to right-side dominance. The laterality of lateral ventricular enlargement was not relate to that of the arm growth., Conclusions: We propose that the main cause of slight lateral ventricular enlargement may not be malnutrition but instead may be hypoxic stress in utero .

Objective: The efficacy of routine brain MRI for term infants admitted to a neonatal intensive care unit (NICU) has not been well studied. This study aimed to investigate the types and frequencies of abnormal findings on routine brain MRI and the predictors of abnormality for term infants in an NICU setting., Methods: We examined the results of routine brain MRI of 239 term infants who were hospitalized in the NICU. Data on the perinatal factors were also collected, and the association with MRI abnormalities was assessed., Results: Of the 239 MRI scans, we found abnormal findings in 52 (21.8%) patients. Intracranial hemorrhage accounted for 74% of the abnormal findings, including subdural, intraparenchymal, cerebellar, and subependymal hemorrhages. Twenty-six percent of these were ischemic lesions, including cerebral infarction, white matter abnormal intensities, and cystic periventricular leukomalacia (PVL). Five (2.1%) MRI scans required detailed examination or were known to be associated with a poor neurological prognosis. No patient needed treatment for the findings. An Apgar score ≤7 points at 5 min was identified as a perinatal factor significantly associated with abnormal MRI findings (adjusted OR = 3.034, 95% CI: 1.107-8.315, p  = .031)., Conclusion: The efficacy of routine brain MRI for term infants admitted to the NICU was limited. Routine brain MRI is not recommended for this population.

Guanidine-bridged nucleic acid (GuNA) is a novel 2',4'-bridged nucleic acid/locked nucleic acid (2',4'-BNA/LNA) analog containing cations that exhibit strong affinity for target RNA and superior nuclease resistance. In this study, Malat1 antisense oligonucleotide (ASO) bearing GuNA was evaluated for target knockdown (KD) activity and tolerability. The GuNA ASO did not interfere with RNase H recruitment on the target RNA/ASO heteroduplex and did show potent target KD activity in a skeletal muscle-derived cell line equivalent to that of the LNA ASO under gymnotic conditions, whereas almost no KD activity was observed in a hepatocyte-derived cell line. The GuNA ASO exhibited potent KD activity in various tissues; the KD activity in the skeletal muscle was equivalent with that of the LNA ASO, but the KD activities in the liver and kidney were clearly lower compared with the LNA ASO. In addition, despite the higher accumulation of the GuNA ASO in the liver, levels of aspartate aminotransferase and alanine aminotransferase with the GuNA ASO administration were not elevated compared with those induced by the LNA ASO. Our data indicate that the GuNA ASO is tolerable and exhibits unique altered pharmacological activities in comparison with the LNA ASO in terms of the relative effect between liver and skeletal muscle.

Aim: Antisense oligonucleotide (ASO) has the potential to induce off-target effects by inadvertent binding of ASOs to unintended RNAs that have a sequence similar to the target RNA. In the present study, we focused on the association between oligonucleotide length and off-target effects. Oligonucleotide extension is assumed to have bilateral effects on hybridization-dependent changes in gene expression, i.e., one is the decrease of off-target effects based on the reduced number of off-target candidate genes with perfect matches, and the other is the increase of off-target effects based on the increased binding affinity between the ASO and the complementary RNAs that leads to better tolerability for mismatches., Methods: To determine the effects of oligonucleotide extension of gapmer ASOs on off-target effects, an extensive microarray analysis was performed using human cells treated with a 14-mer gapmer ASO and the extended 18-mer derivatives with the same core 14-mer region., Results and Discussion: Our data indicated that change in gene expression in the cells treated with 18-mer ASOs was significantly smaller than those with a 14-mer ASO, showing the decrease of off-target effects by oligonucleotide extension., (© 2022. The Author(s).)

Development of low-clearance (CL) compounds that are slowly metabolized is a major goal in the pharmaceutical industry. However, the pursuit of low intrinsic CL (CL int ) often leads to significant challenges in evaluating the pharmacokinetics of such compounds. Although in vitro-in vivo extrapolation is widely used to predict human CL, its application has been limited for low-CL int compounds because of the low turnover of parent compounds in metabolic stability assays. To address this issue, we focused on chimeric mice with humanized livers (PXB-mice), which have been increasingly reported to accurately predict human CL in recent years. The predictive accuracy for nine low-CL int compounds with no significant turnover in a human hepatocyte assay was investigated using PXB-mouse methods, such as single-species allometric scaling (PXB-SSS) approach and a novel physiologically based scaling (PXB-PBS) approach that assumes that the CL int per hepatocyte is equal between humans and PXB-mice. The percentages of compounds with predicted CL within 2- and 3-fold ranges of the observed CL for low-CL int compounds were 89% and 100%, respectively, for both PXB-SSS and PXB-PBS approaches. Moreover, the predicted CL was mostly consistent among the methods. Conversely, the percentages of compounds with predicted CL within 2- and 3-fold ranges of the observed CL for low-CL int compounds were 50% and 63%, respectively, for multispecies allometric (MA) scaling. Overall, these PXB-mouse methods were much more accurate than conventional MA scaling approaches, suggesting that PXB-mice are useful tools for predicting the human CL of low-CL int compounds that are slowly metabolized., (© 2021 Mitsubi Tanabe Pharma Corporation. Clinical and Translational Science published by Wiley Periodicals LLCon behalf of American Society for Clinical Pharmacology and Therapeutics.)

A 78-year-old man presented with hypercalcemia and renal disease with high serum IgG4 and positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), exhibiting sarcoidosis-like chest findings. A renal biopsy revealed tubulointerstitial nephritis, membranous nephropathy (MN), and sub-capsular lymphoid aggregates without fulfilling the diagnostic criteria of IgG4-related disease or sarcoidosis. Steroid therapy ameliorated the serological and renal abnormalities. After 5 years, following gradual increases in the neutrophil count and upper respiratory infection (URI), necrotizing crescentic glomerulonephritis (NCGN) developed with an increased serum MPO-ANCA level. These results suggest that in the presence of MPO-ANCA in immune senescence, the persistent neutrophil increase with URI may lead to the development of NCGN.

Background: Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin., Methods: This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission., Results: Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5-9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54-17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023)., Conclusions: PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC., Trial Registration: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020., (© 2021. The Author(s).)

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.)

Objective: The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in healthy infants., Methods: We examined 1089 healthy infants who weighed at least 2000 g and were born at a gestational age of at least 36 weeks. We assessed the presence of ventricular enlargement when an apparent space was observed in the frontal horn or body of the lateral ventricle of the brain by a transfontanel ultrasound scan. We investigated the relationships between slight lateral ventricular enlargement and various prenatal factors., Results: Slight lateral ventricular enlargement was observed in 497 (45.6%) infants. Slight lateral ventricular enlargement was related to maternal anemia ( p  = .004; odds ratio = 1.630; 95% CI: 1.168-2.276), threatened premature labor ( p  = .010; odds ratio = 1.441; 95% CI: 1.093-1.900), and diabetes mellitus ( p  = .022; odds ratio = 2.020; 95% CI: 1.109-3.682) using multiple logistic regression analysis. The birth weight of the infants with slight lateral ventricular enlargement was heavier than that of those without ventricular enlargement at 36-40 weeks of gestation. Forty infants with ventricular enlargement had head circumferences greater than the 90th percentile, while only one infant without ventricular enlargement did ( p  < .001). In addition, 22 infants with ventricular enlargement had head circumferences less than the 10th percentile, while only 4 infants without ventricular enlargement did ( p  < .001). In 497 infants with ventricular enlargement, the numbers of infants with left side dominant, equivalent, and right side dominant ventricular enlargement were 289 (58.1%), 110 (22.1), and 98 (19.7%), respectively., Conclusions: Slight lateral ventricular enlargement could be caused by several pathological conditions in utero , including brain atrophy, ventricular enlargement, the influence of blood flow in the brain, and various pathological changes in different brain regions.

Extracellular vesicles (EVs) are lipid bilayer particles that are released by various cells and provide a real-time snapshot of the state of these cells in tissue in a noninvasive manner. EVs contain components, including mRNA, miRNAs, proteins, and metabolites. Therefore, EVs hold promise for the discovery of liquid biopsy-based biomarkers for disease diagnosis. In the present study, metabolome analysis of urine EVs in rats with kidney injury caused by cisplatin and puromycin aminonucleoside was performed using liquid chromatography/mass spectrometry to identify candidate biomarkers that reflect the type and extent of injury in drug-induced nephrotoxicity. A total of 396 metabolites were detected in urine EVs, of which 65 were identified as potential biomarkers in urine EVs of drug-induced nephrotoxicity. Pathway analysis revealed that these metabolites may reflect changes occurring within damaged cells during kidney injury, suggesting that metabolomics of urine EVs could be a useful informative tool., 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 © 2021 Elsevier Inc. All rights reserved.)

We analyzed the clinical features of 157 patients admitted to 11 institutions in the Kagawa Prefecture for volvulus of the sigmoid colon. The following were the background information of the patients:median age, 79.0 years;male-to-female ratio, 102:55;median body mass index, 20.0kg/m 2 ;and the proportion of patients with performance status ≥3, 43.9%. Abdominal bloating and pain were the chief complaints. During hospitalization, endoscopy and endoscopic detorsion were performed 157 and 100 times, respectively. An accidental complication was observed in 3 cases, all of which were intestinal perforations. Surgery, which was indicated for ischemia, was performed in 62 of the 157 cases. Endoscopy is useful in the diagnosis of ischemia, which can be treated following an early diagnosis. Of the 157 patients, 19 died, whereas the rest were discharged. The risk factors for death were age ≥80 years and creatinine kinase level ≥200IU/L.

Objective: The goal of this study was to investigate the prognosis of infants with neonatal respiratory inhibition syndrome (NRIS). Methods: Infants with a gestational age of at least 36 weeks and a birth weight of at least 2000 g who were born at Nara Prefecture General Medical Center, in Nara, Japan, between March 2013 and June 2016 were screened for NRIS using our established method. NRIS was defined as severe hypoxemia caused by respiratory inhibition immediately after crying (RIAC) or gastroesophageal reflux (RIGER) or as a respiratory pause during feeding (feeding hypoxemia), accompanied clinically by central cyanosis and a decrease in SpO 2 to less than 70%. All infants were monitored using pulse oximetry immediately after birth. Diagnosis of RIAC, feeding hypoxemia, and RIGER are based on observation by both parents and medical staff as well as on on-screen computer analysis using specific software. All infants were examined at a one-month check-up. Parents of the infants who experienced one or more episodes of NRIS accompanied by a decrease in SpO 2 to less than 70% for more than approximately 60 s received a questionnaire by mail about their child's development. We conducted a logistic regression analysis with developmental problems as the dependent variable. Results: NRIS was observed in 362 (28.5%) infants; 216 (17.0%) infants showed RIAC, 254 (20.0%) infants showed feeding hypoxemia, and 54 (4.2%) infants showed RIGER. Although all infants were monitored in the maternity ward nursery, 184 (85.2%) infants with RIAC and 111 (43.7%) infants with feeding hypoxemia were overlooked. All infants with NRIS were found to have successfully recovered at one month after birth. Sixty-two cases were examined in the follow-up study by the mailed questionnaire. The median age of the subjects at time of study was 22 months. Fourteen cases (22.6%) exhibited developmental problems including delayed speech development, stereotyped interests and behaviors, sensory disturbance, hyperactivity, delayed motor development, and short stature. Developmental problems tended to relate to shorter gestational age (odds ratio, 0.622; p  = .068; 95% CI, 0.373-1.036), smaller birth weight (odds ratio, 0.998; p  = .069; 95% CI, 0.997-1.000), and maximum duration of SpO 2 to less than 70% by RIAC (odds ratio, 1.009; p  = .086; 95% CI, 0.999-1.020). All cases had experienced severe hypoxemia accompanied by a decrease in SpO 2 to less than 60%. Seven cases had experienced prolonged hypoxemia accompanied by a decrease in SpO 2 to less than 70% for at least 2 min. Among the subjects, 19 infants were examined closely, and their natural course of NRIS was observed in the neonatal intensive care unit. No cases demonstrated abnormal findings with blood examinations, chest-abdominal X-ray, echocardiogram, laryngoendoscopy, hearing loss screening, or mass screening. Only one case had a small intracranial hemorrhage as evidenced in a magnetic resonance imaging of the head. Conclusions: The infants with severe NRIS tended to have developmental problems. Spreading knowledge about NRIS worldwide is thought to be very important.

Superior mesenteric artery syndrome, a rare cause of duodenal obstruction, occasionally requires surgery. Bowel emphysema might also require surgery and might be an ominous sign of a serious condition. We report the case of a 69-year-old Japanese man with left pneumothorax who was also diagnosed as having bowel emphysema and superior mesenteric artery syndrome simultaneously without serious infection after surgery for the pneumothorax. Following gastric decompression via a nasogastric tube, his general condition resolved quickly with no need for surgical intervention. Prompt and precise diagnosis by computed tomography and both adequate judgment and treatment can avoid surgery in such cases.

Antisense oligonucleotide (ASO) has the potential to induce off-target effects due to complementary binding between the ASO and unintended RNA with a sequence similar to the target RNA. Conventional animal studies cannot be used to assess toxicity induced by off-target effects because of differences in the genome sequence between humans and other animals. Consequently, the assessment of off-target effects with in silico analysis using a human RNA database and/or in vitro expression analysis using human cells has been proposed. Our previous study showed that the number of complementary regions of ASOs with mismatches in the human RNA sequences increases dramatically as the number of tolerated mismatches increases. However, to what extent the expression of genes with mismatches is affected by off-target effects at the cellular level is not clear. In this study, we evaluated off-target effects of gapmer ASOs, which cleave the target RNA in an RNase H-dependent manner, by introducing the ASO into human cells and performing microarray analysis. Our data indicate that gapmer ASOs induce off-target effects depending on the degree of complementarity between the ASO and off-target candidate genes. Based on our results, we also propose a scheme for the assessment of off-target effects of gapmer ASOs., (© 2019 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: Although tertiary hospitals have successfully introduced ASPs by antimicrobial stewardship teams, lots of community hospitals without pediatric infectious disease specialists have difficulty implementing ASP. We present a successful implementation of simple and feasible NICU antimicrobial stewardship program in a Japanese community hospital., Method: We developed a protocol of antimicrobial treatment in our NICU department and have implemented the protocol from September 2017. The protocol consists of start and stop of criteria antimicrobial treatment, weekend report of blood culture result from microbiology department and stopping ordering antimicrobials beforehand for the next day. We compared days of therapy (DOT) during the post-implementation period (September 2017 to August 2018) with that of pre-implementation period (March 2013 to August 2017)., Result: In pre- and post-ASP implementation periods, 913 and 194 patients were analyzed. DOT was 175.1 and 41.6/1000 patient-days, respectively (p < 0.001) with 76.2% reduction. The percentage of neonates who had any antimicrobials and the percentage of prolonged antimicrobial treatments among neonates who had any antimicrobials decreased significantly (55.3% vs 20.6%, p < 0.001 and 65.0% vs 32.5%, p < 0.001). The protocol compliance rates were also significantly different (55.4% vs 95.4%; p < 0.001). The methicillin-resistant rate of S.aureus rates were significantly reduced in post-ASP period (31.1% vs 12.9%; p = 0.002)., Conclusion: This ASP program was easily implemented in a NICU department of a community hospital and significantly reduced antimicrobial prescription. This kind of simple protocol may be successfully scaled-up in resource limited community hospitals without no pediatric infectious disease specialists or antimicrobial stewardship team., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Alcohol consumption and subsequent sleeping in unusual positions often causes compression neuropathies. In this case, we experienced a unique case of bilateral leg palsy after sleeping in a forward bending position that was photographed by his colleague. We expected that prolonged blockage of the circulation of the femoral arteries resulted in bilateral thigh compartment syndromes (TCSs), leading to sciatic nerve damage. The muscle MRI and needle EMG support this hypothesis. A couple of similar cases have been reported, but the causes of TCS was undetermined due to lack of medical history. This case illustrates that atraumatic compartment syndrome with sciatic nerve palsy can be occurred by prolonged unusual positions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: C-reactive protein (CRP) has limited placental transportability. Relying on CRP level in umbilical cord blood alone is an inaccurate way to predict early onset neonatal sepsis, and we retrospectively reviewed the clinical courses of neonates with elevated CRP in umbilical cord blood., Methods: This study was a retrospective case review of neonates with elevated CRP in umbilical cord blood (>0.5 mg/dL) in the Nara Prefecture General Medical Center, Nara, Japan between February 2013 and August 2017. We investigated the association of maternal and neonatal factors with neonatal clinical course. Then, we compared the cases of neonates with and without elevated CRP in umbilical cord blood., Results: The subjects consisted of a total of 22 neonates with elevated CRP in umbilical cord blood and 344 neonates without elevated CRP in umbilical cord blood. Of the 22 neonates with elevated CRP, 18 had some symptoms of sepsis at birth, but the symptoms of 85% of the symptomatic patients resolved ≤24 h after birth. Two neonates with elevated CRP in umbilical cord blood had bacteremia, and they had poor prognoses. Elevated CRP in umbilical cord blood was associated with length of antimicrobials (P = 0.021), immature/total neutrophil ratio (P = 0.017), and pathological chorioamnionitis (CAM; P = 0.028) on multivariable logistic regression analysis., Conclusion: Elevated CRP in umbilical cord blood was associated with pathological CAM. Most symptoms of sepsis resolved <24 h after birth., (© 2019 Japan Pediatric Society.)

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.)

A 74-year-old male with lung squamous cell carcinoma who was treated with the anti PD-1 antibody nivolumab developed frequent diarrhea four months after initiating treatment. However, his condition did not improve despite prednisolone at 20mg. Endoscopic examination revealed loss of vascular pattern, erosions, and mucosal friability, resembling ulcerative colitis. Colonoscopy revealed punch-out ulcers in the affected mucosa. Therefore, he was definitively diagnosed with severe colitis caused by immune checkpoint inhibitor treatment and cytomegalovirus colitis. Nivolumab was discontinued, and he was treated with 60mg prednisolone and ganciclovir. Although his colitis improved, he developed pneumonia and died thereafter. This case highlights adverse events that are associated with immune checkpoint inhibitors which should be treated properly.

Emphysematous cystitis is an uncommon acute infection of the underlying bladder musculature and mucosa, caused by gas-producing organisms. Here we describe an 87-year-old woman with diabetes mellitus and emphysematous cystitis who was successfully treated with hyperbaric oxygen (HBO2) therapy. Her predisposition of diabetes and infection with gas-producing bacteria was considered to precede the development of emphysematous cystitis. Computed tomography revealed gas accumulation in the bladder wall and lumen. Antibiotics and HBO2 therapy were administered. HBO2 therapy may be beneficial due to the improvement in oxygenation of the tissues affected by the disease. HBO2 is a useful adjunct therapy for the management of severe emphysematous cystitis., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Objective: In our previous studies, we documented that threatened premature labor and asymmetrical intrauterine growth restriction were risk factors for respiratory inhibition. The goal of this study was to determine the cause of respiratory inhibition by considering perinatal risk factors., Methods: We examined 1497 infants with a gestational age of 36 weeks or greater. All infants were monitored using pulse oximetry and examined via cranial sonography. Respiratory inhibition was defined as severe hypoxemia caused by respiratory inhibition immediately after crying or gastroesophageal reflux or as a respiratory pause during feeding. We examined the relationships between respiratory inhibition and perinatal factors and speculated on the cause of respiratory inhibition., Results: The median gestational age, birth weight, Apgar score at 1 min, and Apgar score at 5 min of the subjects were 38.9 weeks, 2930 g, 8.0 points, and 9.0 points, respectively. Respiratory inhibition was observed in 422 infants. Lateral ventricle enlargement and increased echogenicity in the ganglionic eminence were observed in 417 and 516 infants, respectively. Respiratory inhibition was significantly correlated with shorter gestational periods, twin pregnancies, lateral ventricle enlargement, and increased echogenicity in the ganglionic eminence., Conclusions: We speculate that umbilical cord compression is a major cause of respiratory inhibition.

Background/aims: The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients., Methods: IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians' global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation., Results: A total of 429 IBD (378 ulcerative colitis, 51 Crohn's disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78-3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81-3.11; P=0.172]). Based on the physicians' global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months' observation period. The overall eradication rate was 84.0%-comparable to previous reports in non-IBD patients., Conclusions: H. pylori eradication therapy does not alter the short-term disease activity of IBD.

Objective: Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC., Materials and Methods: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan-Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered., Results: Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis., Conclusions: The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.

In plant cytokinesis, actin is thought to be crucial in cell plate guidance to the cortical division zone (CDZ), but its organization and function are not fully understood. To elucidate actin organization during cytokinesis, we employed an experimental system, in which the mitotic apparatus is displaced and separated from the CDZ by centrifugation and observed using a global-local live imaging microscope that enabled us to record behavior of actin filaments in the CDZ and the whole cell division process in parallel. In this system, returning movement of the cytokinetic apparatus in cultured-tobacco BY-2 cells occurs, and there is an advantage to observe actin organization clearly during the cytokinetic phase because more space was available between the CDZ and the distantly formed phragmoplast. Actin cables were clearly observed between the CDZ and the phragmoplast in BY-2 cells expressing GFP-fimbrin after centrifugation. Both the CDZ and the edge of the expanding phragmoplast had actin bulges. Using live-cell imaging including the global-local live imaging microscopy, we found actin filaments started to accumulate at the actin-depleted zone when cell plate expansion started even in the cell whose cell plate failed to reach the CDZ. These results suggest that specific accumulation of actin filaments at the CDZ and the appearance of actin cables between the CDZ and the phragmoplast during cell plate formation play important roles in the guidance of cell plate edges to the CDZ.

Recently, the use of filters has come into light for sanitizing water plants. This study investigated the role of heat-tolerant ultrafilters (UFs) for the remediation of reverse osmosis (RO) plants using periodic thermal disinfection. Two completely identical RO plants (RO plants A and B) were installed in 2006 for surgical hand antisepsis in the operating theater. RO water was stored in the 300 L storage tank and recirculated in the 190 meter-long loop delivering water to 12 faucets in each RO plant. Periodic thermal disinfection came into practice periodically when a UF module was retrofitted to the recirculation loop of each RO plant in 2010. Endotoxin was monitored closely before and after thermal disinfection. Before UF modules were retrofitted, endotoxin increased to a maximum of 0.301 EU/mL in RO plant A and 1.446 EU/mL in RO plant B after thermal disinfection, respectively. Since a UF module was retrofitted to each RO plant in 2010, endotoxin has been continuously below 0.025 EU/mL in RO plant A and exceeded this level five times in RO plant B. On one occasion, endotoxin increased in all samples collected simultaneously after solenoid valves were replaced in the recirculation loop near the air conditioner outlet. At this time, the inside of the pipework was exposed to the ventilation airflow. After the valves were replaced again, this time with the workplace isolated using a curing sheet, endotoxin decreased. On the other occasions, endotoxin increased only in one sample and decreased after thermal disinfection. Annually replaced UF modules were examined twice for estimating the amounts of immobilized endotoxin. The estimated amounts decreased in 2013 by the order of 10 -3 in comparison with those in 2011 in both RO plants. The present study suggested that UFs acted synergistically with periodic thermal disinfection for the remediation of RO plants., (© PDA, Inc. 2018.)

Background: Admission to the neonatal intensive care unit (NICU) due to respiratory distress is determined according to subjective clinician judgement. We investigated prenatal factors predictive of NICU admission in neonates with respiratory distress., Methods: This case-control study was conducted at Nara Prefecture General Medical Center, Nara, Japan, from February 2013 to April 2017 and included neonates with birthweight ≥2,000 g, ≥36 weeks of gestational age, who required oxygen due to respiratory distress at birth. The cases consisted of neonates admitted to the NICU, and the control group consisted of neonates who did not require NICU admission. Perinatal factors between the groups were compared, and multivariate logistic regression analysis carried out to evaluate predictive factors., Results: The NICU group consisted of 94 neonates, and the control group, 417 neonates during the period reviewed. On multivariate analysis, maternal anemia (OR, 2.97; 95%CI: 1.42-6.21), infertility treatment (OR, 2.79; 95%CI: 1.36-5.71), threatened preterm labor (OR, 2.16; 95%CI: 1.10-4.23), premature rupture of membranes (OR, 5.30, 95%CI: 2.52-11.17), fibroids (OR, 6.06; 95%CI: 1.57-23.41), history of uterine surgery (OR, 3.53, 95%CI: 1.13-11.06), abruptio placentae (OR, 10.21; 95%CI: 1.83-57.17), intrauterine growth restriction (OR, 6.69; 95%CI: 1.96-22.85), and having twins (OR, 0.23; 95%CI: 0.09-0.58) were significant prenatal predictors of NICU admission., Conclusion: Factors that potentially predict NICU admission were identified. Clinicians may wish to consider these factors when treating neonates with respiratory distress., (© 2018 Japan Pediatric Society.)

Background: Routine catheter tip cultures are not recommended because some cases of colonization, such as with Staphylococcus aureus, can lead to subsequent bacteremia. To evaluate the safety of colonization without antimicrobial treatment, as well as the effectiveness of routine catheter tip cultures in the neonatal intensive care unit (NICU), we performed a retrospective data analysis in a Japanese community hospital., Methods: We reviewed all peripherally inserted central venous catheter tip culture results from the NICU ward between April 2012 and June 2017 and noted outcome (i.e. antimicrobial treatment or subsequent infection). We then performed a cost analysis for routine catheter tip culturing on patients who were symptom free during the study period., Results: Of the 93 positive cases in 80 patients from 1,051 catheter tip cultures, seven patients had suspected infection and were treated with antimicrobials. The other 73 symptom-free, positive patients had no subsequent or exacerbated symptoms indicative of an infection, and did not have antimicrobial treatment. The total cost for catheter tip culturing during the study period was ¥548 731. After excluding patients with symptoms of infection at the time of culture, the efficacy of routine catheter tip cultures on symptom-free patients was estimated to be zero., Conclusion: Symptom-free colonization did not affect clinician management in this study, and all colonized patients without suspected infection were safely managed without antimicrobials. Furthermore, routine catheter tip culturing was not cost-effective; therefore, this practice may be no longer recommended in the NICU., (© 2018 Japan Pediatric Society.)

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.)

We developed an acylative desymmetrization of meso-1,2-diols using a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1h with tert-alcohol substituents. The reaction proceeds with a wide range of acyclic meso-1,2-diols and six-membered-ring meso-1,2-diols to provide a monoacylate selectively with a high enantiomeric ratio (er). Only 0.1 mol % of the catalyst facilitated the reaction within a short reaction time (3 h) to afford enantio-enriched monoacylated products in moderate to good yield. Several control experiments revealed that the tert-alcohol units of catalyst 1h play a significant role in achieving high catalytic activity, chemoselectivity of monoacylation, and enantioselectivity.

Objective: The aim of this study was to determine the clinical significance of slightly lateral ventricular enlargement., Methods: We examined 1151 infants with a gestational age of 36 weeks or greater. We assessed for the presence of ventricular enlargement when apparent space was observed in the frontal horn or body of lateral ventricle by a transfontanel ultrasound scan., Results: Two hundred and forty-eight infants had ventricular enlargement. The atrial widths in most infants were less than 10 mm. Ventricular enlargement correlated with Cesarean delivery, gestational age, birth weight, respiratory disturbance at delivery and respiratory inhibition after crying (RIAC). Ventricular enlargement could be divided into three types by ultrasound findings. Forty-five infants showed only enlargement of the anterior horn (Type A), 97 infants showed enlargement from the body to the posterior horn (Type B), and 108 infants showed whole enlargement from the anterior to the posterior horn (Type C). The infants with Type A correlated with intrauterine growth restriction, placenta previa, male gender and birth weight. The infants with Type B correlated with cesarean delivery. The infants with Type C correlated with diabetes mellitus, respiratory disturbance at delivery, RIAC and feeding hypoxemia., Conclusions: Slightly lateral ventricular enlargement should be considered clinically significant.

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 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.