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The applicability of bio-chemical grouting as an environmentally friendly method for liquefaction remediation was evaluated. Several combinations of organic and in-organic precipitations methods were conducted to obtain the optimum grouting solution. Organic precipitation method which employs a bio-agent of urease enzyme, promotes the precipitated calcite crystals. Meanwhile, the in-organic method was performed using chemical compounds only, without the bio-agent. Unconfined compression strength tests were conducted to assess the applicability of the grouting solutions for improving the soil strength. The experimental results showed that the organic precipitation produced a high precipitated amount and resulted in a significant improvement in the strength of the soil. The presence of the precipitated materials within the soil grains generated the strength of 272 kPa. The results of this study have elucidated that the organic precipitation method composed of reagents and enzyme of urease may be an alternative soil-improvement technique to prevent liquefaction susceptibility. [ABSTRACT FROM AUTHOR]

Several methods have been established for their various potential applications as soil improvement technique, and recently the application of grouting technique using biological process have been proposed. This study discussed the applicability of enzyme-mediated calcite precipitation (EMCP) in improving the shear strength parameters of sandy soil. In this study, soil specimens were prepared and treated with the grouting solutions composed of urea, calcium chloride, magnesium sulfate and enzyme of urease. Evolutions in the cohesion and internal friction angle of the improved soil were examined through the direct shear tests. The presence of the precipitated materials, comprising 4.1 percent of the soil mass of the treated sand, generated a cohesion of 53 kPa. However, contrary to the improvement of cohesion, the friction angle is relatively constant. It indicated that the application of the EMCP technique has no significant impact on the friction angle. [ABSTRACT FROM AUTHOR]

The relation between concentration of elements and microbial activity in the water samples of Higashi-Hiroshima Campus, Hiroshima University was investigated. Energy dispersive X-ray spectroscopy revealed that microbial mat contains iron, aluminium, silicon and phosphorus. Model experiment revealed that the potassium was adsorbed by living microorganism in the microbial mats, while it was not adsorbed by dead microbial mat. Iron was adsorbed by both living and dead microbial mats. The present results explain the increase in the total b-radioactivity of water sample in summer and the decrease in winte. [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.