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The usefulness of wastewater-based epidemiology (WBE) was proven during the COVID-19 pandemic, and the role of environmental monitoring of emerging infectious diseases has been recognized. In this study, the prevalence of carbapenem-resistant Enterobacterales (CRE) in Japanese environmental samples was measured in the context of applying WBE to CRE. A total of 247 carbapenem-resistant isolates were obtained from wastewater, treated wastewater, and river water. Treated wastewater was shown to be an efficient target for monitoring CRE. The results of the isolate analysis showed that WBE may be applicable to Escherichia coli-carrying New Delhi metallo-β-lactamase (NDM)-type carbapenemase, the Enterobacter cloacae complex and Klebsiella pneumoniae complex-carrying IMP-type carbapenemase. In addition, a certain number of CRE isolated in this study carried Guiana extended spectrum (GES)-type carbapenemase although their clinical importance was unclear. Only a few isolates of Klebsiella aerogenes were obtained from environmental samples in spite of their frequent detection in clinical isolates. Neither the KPC-type, the oxacillinase (OXA)-type nor the VIM-type of carbapenemase was detected in the CRE, which reflected a low regional prevalence. These results indicated the expectation and the limitation of applying WBE to CRE.

The effect of stress concentration on the compressive failure behavior of a carbon fiber composite laminate with an open hole is experimentally and numerically studied. The aspect ratio of the elli...

Crohn's disease (CD) development is thought to involve genetic factors related to immune response as well as environmental factors, such as intestinal bacteria and diet, though no clear cause has yet been identified. In our previous study, we found that the concentrations of linoleic acid, stearic acid, and metabolites in erythrocytes differed between CD patients and healthy subjects. These factors related to lipid metabolism are controlled by Δ6 desaturase (fatty acid desaturase 2, FADS2) and elongase 6 (ELOVL6), respectively. In the present study, we analyzed the gene sequences of FADS2 and ELOVL6 in 52 Japanese CD patients, and then compared mutation frequencies with findings in healthy individuals. Nineteen FADS2 mutations and 33 ELOVL6 mutations were found. Furthermore, a new variant in the promoter region was shown in both genes, though no mutation in the coding region was found in either. For the FADS2 intron, the allele frequency of rs227784 (0.3365; 95% CI = 0.0337-0.01460) was higher than that in healthy subjects (0.0190). Furthermore, allele rs227784 had a greater association with CD (odds ratio = 4.4; 95% CI = 2.1-9.3). As compared with healthy Japanese healthy individuals, no mutations were found with a largely deviated allele frequency in the present CD group. However, the number of patients examined was small, thus the reliability of our results is limited. The present findings regarding genetic effects on CD onset and lipid metabolism may be weak.

In the present study, strain-rate and temperature dependence of the transverse tensile failure mode of unidirectional heat-resistant carbon fiber-reinforced plastics is numerically simulated by finite element analyses. In the analyses, interface failure and matrix failure are represented by cohesive zone modeling and continuum damage mechanics, respectively. For the continuum damage mechanics, Christensen's failure criteria of multi-axial stress states for each strain rate are applied to the matrix properties. Interfacial properties which are obtained by microbond test are introduced into cohesive zone modeling. A time-temperature superposition principle approach is applied in order to translate the difference in temperature as the difference in strain rate. The damage initiation depends on strain rate and temperature, while the cohesive zone modeling is assumed to be temperature- and time-independent. The initial damage starting points and the failure mode are predicted in numerical analysis. The transverse tensile strengths in analysis results are compared with the three-point bending testing results.

Azole resistance of Aspergillus fumigatus is a global problem. The major resistant mechanism is a cyp51A alteration such as mutation(s) in the gene and the acquisition of a tandem repeat in the promoter. Although other azole tolerances and resistant mechanisms such as hmg1 mutation are known, few reports describe studies elucidating non-cyp51A resistance mechanisms. This study explored genes contributing to azole tolerance in A. fumigatus by in vitro mutant selection with tebuconazole, an azole fungicide. After three-round selection, we obtained four isolates with low susceptibility to tebuconazole. These isolates also showed low susceptibility to itraconazole and voriconazole. Comparison of the genome sequences of the obtained isolates and the parental strain revealed a non-synonymous mutation in MfsD (Afu1g11820, R337L mutation) in all isolates. Furthermore, non-synonymous mutations in AgcA (Afu7g05220, E535Stop mutation), UbcD (Afu3g06030, T98K mutation), AbcJ (Afu3g12220, G297E mutation), and RttA (Afu7g04740, A83T mutation), a protein responsible for tebuconazole tolerance, were found in at least one isolate. Clarification by constructing the MfsD R337L mutant suggests that the mutation contributes to azole tolerance. Disruption of the agcA gene and reconstruction of the A83T point mutation in RttA led to decreased susceptibility to azoles. The reversion of T98K mutation to wild type in UbcD led to the level of azole susceptibility comparable to the parental strain. These results suggest that these mutations contribute to lowered susceptibility to medical azoles and to agricultural azole fungicides.

Crohn's disease (CD) development is thought to involve genetic factors related to immune response as well as environmental factors, such as intestinal bacteria and diet, though no clear cause has yet been identified. In our previous study, we found that the concentrations of linoleic acid, stearic acid, and metabolites in erythrocytes differed between CD patients and healthy subjects. These factors related to lipid metabolism are controlled by Δ6 desaturase (fatty acid desaturase 2, FADS2) and elongase 6 (ELOVL6), respectively. In the present study, we analyzed the gene sequences of FADS2 and ELOVL6 in 52 Japanese CD patients, and then compared mutation frequencies with findings in healthy individuals. Nineteen FADS2 mutations and 33 ELOVL6 mutations were found. Furthermore, a new variant in the promoter region was shown in both genes, though no mutation in the coding region was found in either. For the FADS2 intron, the allele frequency of rs227784 (0.3365; 95% CI = 0.0337-0.01460) was higher than that in healthy subjects (0.0190). Furthermore, allele rs227784 had a greater association with CD (odds ratio = 4.4; 95% CI = 2.1-9.3). As compared with healthy Japanese healthy individuals, no mutations were found with a largely deviated allele frequency in the present CD group. However, the number of patients examined was small, thus the reliability of our results is limited. The present findings regarding genetic effects on CD onset and lipid metabolism may be weak.

We propose a viscoelastic/plastic constitutive equation for viscoelastic media based on irreversible thermodynamics and the viscoelastic theory. Uniaxial tensile tests on a TriA-X polyimide resin are performed at different temperatures and strain rates to determine the material parameters for the constitutive equation. In the numerical analysis, the FORTRAN programming language is used to apply the proposed equation to the matrix resin. Transverse tensile failure analysis is performed on the unidirectional carbon fiber reinforced plastic (CFRP) in constant strain rate condition after holding constant strain. In this condition, the failure strength is lower than the static tensile strength. The same tendency is observed in the three-point bending fracture test of the unidirectional CFRP. The proposed model expresses the accumulation of resin damage while holding a constant strain and predicts the residual strength and lifetime of the unidirectional CFRP.

In this chapter, how unidirectional fiber-reinforced composites fail under transverse tensile loading is described, mainly in terms of numerical simulation. The failure morphology and tensile strength change with strain rate and temperature are introduced. Two-dimensional micromechanical periodic unit cell simulation is performed considering the continuum damage mechanics for matrix failure and cohesive zone modeling for interface failure. Information on how to model the micromechanical periodic unit cell of the composite representative cross-section is provided. The key technology of this modeling is being able to simulate the failure mode transition from the interface failure dominant pattern to the matrix failure dominant pattern with temperature elevation or strain rate decrease.

In the present study, strain-rate dependence and temperature dependence of failure mode are numerically simulated by finite element analyses. In the analyses, interface failure and matrix failure are expressed by cohesive zone modeling and continuum damage mechanics, respectively. It is assumed that the damage initiates dependently of strain rate and temperature, and cohesive zone modeling is assumed to be temperature- and time-independent. In the continuum damage mechanics, Christensen’s failure criterion of multi-axial stress states for each strain rate are applied into the resin properties. Interfacial strength which is obtained by microbond test is introduced into cohesive zone modeling. When temperature is high and/or strain rate is low, matrix crack occurs very often and the failure mode is matrix-failuredominant mode. On the other hand, when temperature is low and/or strain rate is high, interface crack significant, i.e. failure mode becomes interface-crack-dominant mode.

Abuse of volatile organic solvents among youth remains a major social problem in Japan. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a so-called "gate-way drug" for users. Psychological dependence assessment systems have been established for drug inhalation using the conditioned place preference (CPP) procedure. We found toluene produced the rewarding effect in this new CPP system. The mesolimbic dopamine pathway, which includes dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain and their targets in the limbic forebrain, especially the nucleus accumbens (NAC), is one of the most important substrates for the development of psychological dependence on drugs such as stimulants, cocaine, and heroin. Recently, it has indicated that the VTA-NAC pathway (monoamine system) may play an important role of the expression of psychological dependence on the volatile organic solvent toluene. Clarification of organic solvent's mechanism for the development of psychological dependence focusing on the monoamine system can be exploited for the new medicine and useful treatments for dependence on toluene.

The effect of barium, a putative blocker of G-protein-activated inwardly rectifying potassium (GIRK) channels, on naltrexone-precipitated withdrawal signs in morphine-dependent mice was investigated. Mice were chronically treated with morphine (8-45 mg/kg) for 6 days. The morphine-dependent mice were then given naltrexone (1 and 3 mg/kg), after which they showed several somatic signs of withdrawal, as well as conditioned aversion, increased cortical noradrenaline turnover, and decreased dopamine turnover in the limbic forebrain. Pretreatment with barium (1.25 and 2.5 nmol) significantly potentiated the naltrexone-precipitated conditioned aversion and augmented the decrease in dopamine turnover in the limbic forebrain. However, barium pretreatment did not affect the naltrexone-precipitated somatic signs of withdrawal and increased cortical noradrenaline turnover. These findings suggest that modification of GIRK channels may be involved in the expression of aversion to morphine withdrawal mediated through the dopaminergic system but it is not involved in the somatic signs of morphine withdrawal mediated through the noradrenergic system.

Abuse of volatile organic solvents among youth remains a major social problem. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a so-called "gateway drug" for users. Most research regarding organic solvents has until now focused on their neurotoxicity, specifically examining the mechanism of neuron death in terms of the involvement of substances such as nerve growth factor. However, systems to assess psychological dependence on volatile organic solvents that take into account the mechanism involved in the development of this dependence have not been established due to the difficulty of creating animal models. The conditioned place preference procedure, which can easily assess whether psychological dependence has been formed, has been phased in in recent years, and dependence assessment systems have been established for drug inhalation. There have also been new research developments regarding dependence on volatile organic solvents. The importance of mesolimbic dopamine neurons has been indicated in the expression of CNS stimulant action and the development of psychological dependence on drugs such as stimulants, cocaine, and heroin, which are typical abused drugs. It has recently become apparent that the increase in dopamine release in the nucleus accumbens accompanying activation of mesolimbic dopamine neurons, as has conventionally been proposed, is important to the expression of CNS stimulant action and the formation of psychological dependence in response to inhalation of toluene, a volatile organic solvent. Furthermore, research with regard to organic solvents' site of action is also proceeding based on studies using molecular biological techniques. Research regarding toluene is progressing, and the importance of receptors that gate ion channels such as N-methyl-D-aspartate (NMDA) and y-aminobutyric acid (GABA)A receptors as candidates for toluene's site of action has been indicated. Clarification of organic solvents' mechanism for the development of psychological dependence is expected to progress, thanks to analysis focusing on such new sites of action.

Toluene and many toluene-containing products are abused via inhalation. Previous investigations have used the place preference paradigm to evaluate the rewarding effects of commonly abused drugs such as morphine, cocaine, and amphetamine. A conditioning paradigm of toluene inhalation was developed in order to estimate the rewarding effect in mice. Conditioning sessions (five for toluene, five for air) were conducted twice daily for 5 days using a newly developed airtight inhalation shuttlebox (15×30×15 cm: w×l×h), which was divided into two compartments of equal size. One compartment was white with a textured floor, and the other was black with a smooth floor. All conditioning sessions were 20 min in duration, with a minimum of 7 h between sessions. Test sessions were carried out 1 day after the final training session with mice in a drug-free state. The time spent in each compartment during a 20-min session was measured using a digital video camera. Exposure to toluene vapors (700–3200 ppm) produced a significant conditioned place preference in mice. These results suggest that the conditioned place preference procedure using the newly developed airtight inhalation shuttlebox constitutes an important tool for studying the rewarding effect of abused solvents.

Heterotrimeric guaninenucleotide-binding protein (G protein) plays an obligatory role on a biochemical basis in psycho stimulant-induced psychosis. However, little is known about the contribution of G-protein beta/gamma-subunit-mediated signal transduction. We investigated the expression and function of beta/gamma subunits, especially the beta-1 subunit, using in situ hybridization, immunohistochemistry, and the antisense knockdown technique, to clarify the molecular basis of methamphe,tamine (MAP)-induced behavioral sensitization. Expression in beta-1 subunit mRNA and protein transiently increased in the ventral tegmental area (VTA) of animals acutely treated with MAP. However, after a challenge injection, this increased response was not observed in VTA of animals repeatedly administered MAP. Antisense knockdown of the beta-1 subunit in VTA revealed an increase in the intensity of stereotypy, and an acceleration in the development of behavioral sensitization. These results suggest that G-protein beta-1 in VTA plays an inhibitory role in the establishment of MAP-induced behavioral sensitization. Furthermore, a lack of response in the expression of beta-1 may lead to a decreased inhibition of the development of behavioral sensitization.