トウコウ キョヒ ジドウ セイト ノ ジッタイ ト ソノ ハッタツテキ コウサツ : ゼンコク ジッタイ チョウサ ニ モトズイテ

In order to determine the occurrence rate of school refusal at primary schools and junior high schools, different grades as well as boys and girls treated separately, we conducted a research in the 47 prefectures of Japan. We mailed a questionnaire to the local governor's bureaus in all prefectures. Items included the number of boys and girls, total number of children with long-term absence due to illness, poor economic conditions, school refusal and other reasons in each grade of all elementary and junior high schools within the prefecture. We received answers from 40 prefectures altogether but only in 4 of them were the grades as well as the sexes treated separately. Eight questionnares were excluded from the analysis because of incomplete recordings. The main results are as follows: 1. The number of students who refused to go to school in the 4 prefectures where different grades and the sexes were treated separately was 6,691 (primary school: 775, junior high school: 5916). 2. The average occurrence rate of school refusal in the four prefectures. was 0.038% in primary schools and 0.598% in junior high schools. 3. The boy to girl ratio in primary schools was about 4:3 and in junior high schools about 5:4, with a trend of the boys always having a higher rate of occurrence. 4. The rate of school refusal showed a gradual increase from first to third or fourth grade and it increased dramatically at 4th or 5th grade of the primary school. This tendency was stronger among boys than girls. 5. The rate increased darastically from the 6th grade of elementary school to the first grade of junior high school, and later it increased linearly as a function of grade. 6. In the case of primary school students, we noticed that in those prefectures where the number of children was under 120,000, there appeared an inverse relarionship between the number of children and the occurrence rate, and tlen in prefectures where the number of children fell between 120,000 and 165,000. the occurrence rate was roughly fixed, while in those prefectures where the number of students exceeded 165,000, the occurrence rate trend to increase proportionately with the higher numbers of children. These results suggest that the emergence of school refusal-on the grounds of unsatisfactory development in earlier periods of life-might be closely connected with the unstable mental states during the critical shifting periods of development, the so-called periods of crisis (Trotz-phase) around the age of 9 and 14

Effect of CYP2C19 Polymorphism on Treatment Success in Lansoprazole-Based 7-Day Treatment Regimen for Cure of H. pylori Infection in Japan

Recently, Helicobacter pylori (H. pylori)-positive peptic ulcer patients were treated by a 1-week triple therapy [lansoprazole (LPZ) 30 mg, amoxicillin 750 mg and clarithromycin 200 or 400 mg, each twice daily] without the checking CYP2C19 genotype in Japan. This regimen was done to obtain sufficient cure rates for H. pylori infection using a high dose of LPZ (60 mg/day) without the great cost of having to determine the genotype. However, the failure rate for eradicating H. pylori was reported to be 12.5%. The reasons for this were studied in 33 Japanese patients with H. pylori-positive gastric or duodenal ulcer. Blood samples of the patients were collected to determine the genotype of CYP2C19 and plasma concentrations of LPZ and its metabolites at 3 h postdose on the morning of the 7th day of treatment. H. pylori infection was cured in 25 of the 33 patients (75.8%). The cure rate was highest in the group of poor metabolizers (PM), intermediate in the group of extensive metabolizers of the heterozygous type (htEM) and lowest in the group of extensive metabolizers of the homozygous type (hmEM). The relative ratio of mean plasma concentration for LPZ among the 3 groups was 1.00:1.43:2.93 (hmEM:htEM:PM groups). Our data suggest that success of the eradication is dependent on the CYP2C19-related genotypic status or the plasma concentrations of LPZ in a steady state condition after a multiple dosing regimen; that is to say, checking CYP2C19 is necessary even on occasions when treatment is done by H. pylori eradication methods as performed in Japan

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target