Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

<p>Abstract</p> <p>Background</p> <p>Chlorine dioxide (CD) gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio) is judged as safe on the basis of a battery of toxicological examinations.</p> <p>Methods</p> <p>CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed.</p> <p>Results</p> <p>Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs.</p> <p>Conclusions</p> <p>CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human.</p

Pathologic and Radiographic Studies of Intrahepatic Metastasis Hepatocellular Carcinoma; The Role of Efferent Vessels

The efferent vessel of hepatocellular carcinoma (HCC) and the mechanism and pathogenesis of the high frequency of intrahepatic metastasis in HCC has not yet been clarified. Three hundred ninety-three resected specimens of HCC were examined for tumor thrombosis in the portal vein and the hepatic vein: 231 tumors ≤5 cm in diameter were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens and by percutaneous infusion of radiopaque media into tumor nodules in 8 patients. The mode of tumor spread in HCC progressed from capsular invasion to extracapsular invasion, then to vascular invasion, and finally to intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and portal vein thrombosis (p<0.05, R=0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in 6 tumors. In all 8 patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that intrahepatic invasion by HCC may occur through the portal vein as an efferent tumor vessel

Variation Analysis of CMOS Technologies Using Surface-Potential MOSFET Model, Journal of Telecommunications and Information Technology, 2009, nr 4

An analysis of the measured macroscopic withinwafer variations for threshold voltage (Vth) and on-current (Ion) over several technology generations (180 nm, 100 nm and 65 nm) is reported. It is verified that the dominant microscopic variations of the MOSFET device can be extracted quantitatively from these macroscopic variation data by applying the surface-potential compact model Hiroshima University STARC IGFET model 2 (HiSIM2), which is presently brought into industrial application. Only a small number of microscopic parameters, representing substrate doping (NSUBC), pocket-implantation doping (NSUBP), carrier-mobility degradation due to gate-interface roughness (MUESR1) and channel-length variation during the gate formation (XLD) are found sufficient to quantitatively reproduce the measured macroscopic within-wafer variations of Vth and Ion for all channel length Lg and all technology generations. Quantitative improvements from 180 nm to 65 nm are confirmed to be quite large for MUESR1 (about 70%) and Lmin(XLD) (55%) variations, related to the gate-oxide interface and the gate-stack structuring, respectively. On the other hand, doping-related technology advances, which are reflected by the variation magnitudes of NSUBC (30%) and NSUBP (25%), are found to be considerably smaller. Furthermore, specific combinations of extreme microscopic parameter-variation values are able to represent the boundaries of macroscopic fabrication inaccuracies for Vth and Ion. These combinations are found to remain identical, not only for all Lg of a given technology node, but also for all investigated technologies with minimum Lg of 180 nm, 100 nm and 65 nm

Regulation of NR4A nuclear receptors by p38

In Drosophila, the melanization reaction is an important defense mechanism against injury and invasion of microorganisms. Drosophila tyrosine hydroxylase (TH, also known as Pale) and dopa decarboxylase (Ddc), key enzymes in the dopamine synthesis pathway, underlie the melanin synthesis by providing the melanin precursors dopa and dopamine, respectively. It has been shown that expression of Drosophila TH and Ddc is induced in various physiological and pathological conditions, including bacterial challenge; however, the mechanism involved has not been fully elucidated. Here, we show that ectopic activation of p38 MAPK induces TH and Ddc expression, leading to upregulation of melanization in the Drosophila cuticle. This p38-dependent melanization was attenuated by knockdown of TH and Ddc, as well as by that of Drosophila HR38, a member of the NR4A family of nuclear receptors. In mammalian cells, p38 phosphorylated mammalian NR4As and Drosophila HR38 and potentiated these NR4As to transactivate a promoter containing NR4A-binding elements, with this transactivation being, at least in part, dependent on the phosphorylation. This suggests an evolutionarily conserved role for p38 MAPKs in the regulation of NR4As. Thus, p38-regulated gene induction through NR4As appears to function in the dopamine synthesis pathway and may be involved in immune and stress responses

A population of the Japanese giant salamander Andrias japonicus (Amphibia: Caudata) inhabiting a small stream flowing through a wetland upstream of a dam: A study on the population of small individuals and larval growth in the field

広島県廿日市市飯山のダム上流の湿地を流れる小河川に生息するオオサンショウウオAndrias japonicusの個体群について報告する。本産地は標高が775–795mあり，本種の生息地で最も標高の高い部類に入る。飯山貯水池は1932年より水力発電ダム湖として建造され，その上流は約90年間ダムの下流域と隔離されている。水位の低下した2001年以降は長年人の手の加わっていない湿地となっている。2017–2020年ののべ17日間に渡る調査で，0歳から1歳，2歳と考えられる幼生が多数見つかり，全長210mmの幼体や326–680mmの成体，繁殖巣穴も見つかった。これは独立した繁殖個体群として世代交代している証拠でもある。この個体群からは全長700mmを越える個体が見つかっておらず，全長が小さい傾向がある。また，0歳幼生の全長と確認日の関係を見ると，全長46mmで離散した0歳幼生が，6月から8月にかけて急成長して75mmに達し，10月以降はほとんど成長しないで翌春を迎えることを示唆していた。幼生は主にダム湖であった当時の名残の水草，ヒルムシロPotamogeton distinctusの中から見つかる傾向がある点も特異な点である。ダム湖へ直接流入する源流域の小河川で本種が持続的に繁殖している例として本産地と個体群は稀少な存在であると言える。Here, we describe a population of the Japanese giant salamander Andrias japonicus inhabiting upstream of the Iinoyama Reservoir in Iinoyama, Hatsukaichi City, Hiroshima Prefecture, Japan. The locality is situated at 775–795 m above the sea level and is one of the highest localities in the habitat of this salamander. The Iinoyama Reservoir was originally built as a hydroelectric dam lake in 1932, and its upstream part has remained isolated for nearly 90 years. Since 2001, when the water level dropped, it has become a wetland, albeit not used by human for many years. In surveys over 17 days during 2017–2020, many zero-, first-, and second-year larvae; a juvenile 210 mm in total length (TL); and adults (326–680 mm in TL) as well as a breeding nest were found, providing evidence that the salamanders in this regions constitute an independent breeding population. No individuals measuring over 700 mm in TL were found in this population, and the overall TL tended to be low. Considering the association between the total length and the date of discovery of zero-year larvae, these larvae likely dispersed when they were about 46 mm and rapidly grew from June to August to reach 75 mm; from October, however, they barely grew until the next spring. Interestingly, the larvae were found in the remnants of the dam lake, near the aquatic plant Potamogeton distinctus. The described locality and population present a rare example of continuous breeding of the Japanese giant salamander in a small stream directly flowing into the dam lake

Assessment of Japanese Stimulant Control Law Offenders Using the Addiction Severity Index—Japanese Version: Comparison with Patients in Treatment Settings

The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005–2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The χ2 and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups

The Molecular Outflows in the rho Ophiuchi Main Cloud: Implications For Turbulence Generation

We present the results of CO (J=3-2) and CO (J=1-0) mapping observations toward the active cluster forming clump, L1688, in the rho Ophiuchi molecular cloud. From the CO (J=3-2) and CO (J=1-0) data cubes, we identify five outflows, whose driving sources are VLA 1623, EL 32, LFAM 26, EL 29, and IRS 44. Among the identified outflows, the most luminous outflow is the one from the prototypical Class 0 source, VLA 1623. We also discover that the EL 32 outflow located in the Oph B2 region has very extended blueshifted and redshifted lobes with wide opening angles. This outflow is most massive and have the largest momentum among the identified outflows in the CO (J=1-0) map. We estimate the total energy injection rate due to the molecular outflows identified by the present and previous studies to be about 0.2 L_solar, larger than or at least comparable to the turbulence dissipation rate [~(0.03 - 0.1) L_solar]. Therefore, we conclude that the protostellar outflows are likely to play a significant role in replenishing the supersonic turbulence in this clump.Comment: 37 pages, 9 figures, accepted for publication in The Astrophysical Journa

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

Background: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine. Methods: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study. Results: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r s = 0.531, P = 1.032 × 10−4). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS. Conclusion: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families

Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study

Background: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD). Methods: A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programs between the 2016 and 2017 groups were compared. Results: The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group. Conclusions: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice