A novel A792D mutation in the CSF1R gene causes hereditary diffuse leukoencephalopathy with axonal spheroids characterized by slow progression

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant white matter disease that causes adult-onset cognitive impairment. The clinical manifestations are a variable combination of personality and behavioral changes, cognitive decline, parkinsonism, spasticity, and epilepsy. In 2012, mutations in the gene encoding colony stimulating factor 1 receptor (CSF1R) were identified as the cause of HDLS. As the numbers of reported mutations are limited, the understanding of whole pathogenesis needs accumulation of disease-causing mutations with detailed clinical descriptions. We describe a Japanese family with autosomal dominant adult-onset cognitive impairment and characteristic white matter lesions. Genetic testing revealed a novel p.A792D mutation in the tyrosine kinase domain of CSF1R in two affected family members. The symptom profile of the present cases mostly matched the previously reported cases, with the notable exceptions of late-onset and long disease duration

Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin

土地区画整理事業施行区域における成長曲線を用いた市街化特性の分析: 金沢市における事例研究

金沢大学理工研究域環境デザイン学系Land Readjustment Project has played a major role for land readjustment in urbanizing area in Japan. This paper tries to investigate actual urbanization conditions after Land Readjustment Project in Kanazawa City using Gompertz Curve as a case of the regional central city. It is analyzed based on indices such as urbanization rate in the area from completion of the project and a located zone from the city center, and studied its characteristics applying Gompetz Curve. Other indices, such as types of the lot and the from road, are also used for analysis

建物立地動向からみた区画整理地区における市街化の実態: 金沢市における事例研究

金沢大学理工研究域環境デザイン学系Land Readjustment Project has played a major role for land readjustment in urbanizing area in Japan. This study tries to clarify actual urbanization conditions after Land Readjustment Project in Kanazawa City. Studied types of Projects are Association one and Individual and Joint ones. It is analyzed based on indices, such as land use type of each lot, urbanization rate of the area, referring to elapsed years from completion of the project. Other indices, such as type of the lot and the front road, are also used for analysis. Urbanization of reserved land area is also analyzed comparing to one of the other area

Magnetohydrodynamic stability at the edge region in H-mode plasmas with long edge-localized-mode-free phases in the large helical device

Clear suppression of magnetic fluctuations associated with resistive interchange modes (RICs) is observed during long edge-localized-mode (ELM)-free phases of the H-mode plasma in an outward-shifted configuration of the Large Helical Decice, in which a steep pressure gradient is generated at the plasma edge in the magnetic hill. The ELM-free H-phase is interrupted by large amplitude ELMs which are thought to be induced through nonlinear evolution of the RICs having m  =  1/n  =  1 dominant component (m: poloidal mode number, n: toroidal one). The m  =  1/n  =  1 RIC amplitude is enhanced about 10 times compared with the H-phase level during each ELM. In most of the H-mode shots, the final ELM-free phase returns to L-phase by a large amplitude ELM. In the L-phase, the RIC amplitude is enhanced by a factor of ~3 compared with that in the H-phase, although the edge pressure gradient is reduced considerably. Linear resistive magnetohydrodynamic stability analysis is attempted using experimentally obtained equilibrium profiles. From the numerical analysis, the distance between the location of the steepest pressure gradient and the main mode resonance surface, i.e. the rotational transform ι  =  1, is found to be important for a large growth of the m  =  1/n  =  1 RIC in the H-phase

Inhibition of poly(ADP-ribose) polymerase-1 attenuates the toxicity of carbon tetrachloride

Carbon tetrachloride (CCl4) is routinely used as a model compound for eliciting centrilobular hepatotoxicity. It can be bioactivated to the trichloromethyl radical, which causes extensive lipid peroxidation and ultimately cell death by necrosis. Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) can rapidly reduce the levels of (β-nicotinamide adenine dinucleotide and adenosine triphosphate and ultimately promote necrosis. The aim of this study was to determine whether inhibition of PARP-1 could decrease CCl4-induced hepatotoxicity, as measured by degree of poly(ADP-ribosyl)ation, serum levels of lactate dehydrogenase (LDH), lipid peroxidation,and oxidative DNA damage. For this purpose, male ICR mice were administered intraperitoneally a hepatotoxic dose of CCl4 with or without 6(5H)-phenanthridinone, a potent inhibitor of PARP-1. Animals treated with CCl4 exhibited extensive poly(ADP-ribosyl)ation in centrilobular hepatocytes, elevated serum levels of LDH, and increased lipid peroxidation. In contrast, animals treated concomitantly with CCl4 and 6(5H)-phenanthridinone showed significantly lower levels of poly(ADP-ribosyl) ation, serum LDH, and lipid peroxidation. No changes were observed in the levels of oxidative DNA damage regardless of treatment. These results demonstrated that the hepatotoxicity of CCl4is dependent on the overactivation of PARP-1 and that inhibition of this enzyme attenuates the hepatotoxicity of CCl4

Behavioral factors associated with SARS-CoV-2 infection in Japan.

BACKGROUND: The relative burden of COVID-19 has been less severe in Japan. One reason for this may be the uniquely strict restrictions imposed upon bars/restaurants. To assess if this approach was appropriately targeting high-risk individuals, we examined behavioral factors associated with SARS-CoV-2 infection in the community. METHODS: This multicenter case-control study involved individuals receiving SARS-CoV-2 testing in June-August 2021. Behavioral exposures in the past 2 weeks were collected via questionnaire. SARS-CoV-2 PCR-positive individuals were cases, while PCR-negative individuals were controls. RESULTS: The analysis included 778 individuals (266 [34.2%] positives; median age [interquartile range] 33 [27-43] years). Attending three or more social gatherings was associated with SARS-CoV-2 infection (adjusted odds ratio [aOR] 2.00 [95% CI 1.31-3.05]). Attending gatherings with alcohol (aOR 2.29 [1.53-3.42]), at bars/restaurants (aOR 1.55 [1.04-2.30]), outdoors/at parks (aOR 2.87 [1.01-8.13]), at night (aOR 2.07 [1.40-3.04]), five or more people (aOR 1.81 [1.00-3.30]), 2 hours or longer (aOR 1.76 [1.14-2.71]), not wearing a mask during gatherings (aOR 4.18 [2.29-7.64]), and cloth mask use (aOR 1.77 [1.11-2.83]) were associated with infection. Going to karaoke (aOR 2.53 [1.25-5.09]) and to a gym (aOR 1.87 [1.11-3.16]) were also associated with infection. Factors not associated with infection included visiting a cafe with others, ordering takeout, using food delivery services, eating out by oneself, and work/school/travel-related exposures including teleworking. CONCLUSIONS: We identified multiple behavioral factors associated with SARS-CoV-2 infection, many of which were in line with the policy/risk communication implemented in Japan. Rapid assessment of risk factors can inform decision making

Current Status of Large Helical Device and Its Prospect for Deuterium Experiment

Achievement of reactor relevant plasma condition in Helical type magnetic devices and exploration in its related plasma physics and fusion engineering are the aim of the Large Helical Device (LHD) project. In the recent experiments on LHD, we have achieved ion-temperature of 8.1 keV at 1 × 1019 m−3 by the optimization of wall conditioning using long pulse discharge by Ion Cyclotron Heating (ICH). The electron temperature of 10 keV at 1.6 × 1019 m−3 was also achieved by the optimization of Electron Cyclotron Heating (ECH). For further improvement in plasma performance, the upgrade of the Large Helical Device (LHD), including the deuterium experiment, is planned. In this paper, the recent achievements on LHD and the upgrade of LHD are described