Fine Particulate Matter and Diabetes Prevalence in Okayama, Japan

Many studies have shown an association between long-term exposure to particulate matter having an aerodynamic diameter of 2.5 μm or less (PM2.5) and diabetes mellitus (DM), but few studies have focused on Asian subjects. We thus examined the association between long-term exposure to PM2.5 and DM prevalence in Okayama City, Japan. We included 76,591 participants who had received basic health checkups in 2006 and 2007. We assigned the census-level modeled PM2.5 data from 2006 and 2007 to each participant and defined DM using treatment status and the blood testing. PM2.5 was associated with DM prevalence, and the prevalence ratio (95% confidence interval) was 1.10 (1.00-1.20) following each interquartile range increase (2.1 μg/m3) in PM2.5. This finding is consistent with previous results and suggests that long-term exposure to PM2.5 is associated with an increased prevalence of DM in Okayama City, Japan, where the PM2.5 level is lower than in other cities in Asian countries

Residential proximity to major roads and adverse birth outcomes: a hospital-based study

Background: Exposure to air pollution has been demonstrated to increase the risk of preterm birth and low birth weight (LBW). Although evidence has accumulated on characteristics associated with increased risk of air pollution-related health effects, most studies have been conducted in the adult population and evidence on reproductive outcomes is limited. We examined whether socio-economic position (SEP) and parental characteristics (parental behavior and co-morbidity) modified the relationship between air pollution and adverse birth outcomes. Methods: Data were extracted from a perinatal hospital database based in Shizuoka, Japan. We restricted the analysis to mothers who delivered live-born single births from January 1997 to December 2010 (n = 16,615). Each birth was assigned proximity to major roads. Multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated for the outcomes of preterm birth and term LBW. We stratified subjects by individual/area-level SEP and parental characteristics. We then measured interactions on the additive scale between the respective factors and exposure. Results: Lower SEP at both individual and area levels was associated with the increased occurrence of adverse birth outcomes. Living within 200 m from a major road increased the risk of preterm birth by 1.5 times (95% CI: 1.3-1.9) and LBW by 1.2 times (95% CI: 0.9-1.6). Mothers with lower individual SEP defined by household occupation experienced higher ORs for term LBW (OR = 3.1, 95% CI: 1.2-8.2) compared with those with higher individual SEP. In contrast, mothers who lived in the highest area-level SEP region (i.e., affluent areas) showed slightly higher point estimates compared with those who lived in middle or poor areas. In addition, maternal diabetic and hypertensive status modified the association between proximity and preterm birth, while maternal smoking status modified the association between proximity and term LBW. Conclusions: The present study demonstrated that air pollution is an independent risk factor for adverse birth outcomes. Mothers with lower individual SEP and mothers living in higher SEP region may be susceptible to the adverse effect of air pollution. Maternal diabetic, hypertensive, and smoking status may also increase susceptibility to this air pollution-related health effect

A novel fully covered metal stent for unresectable malignant distal biliary obstruction: results of a multicenter prospective study

Background/Aims Endoscopic self-expandable metal stent (SEMS) placement is currently the standard technique for treating unresectable malignant distal biliary obstructions (MDBO). Therefore, covered SEMS with longer stent patency and fewer migrations are required. This study aimed to assess the clinical performance of a novel, fully covered SEMS for unresectable MDBO. Methods This was a multicenter single-arm prospective study. The primary outcome was a non-obstruction rate at 6 months. The secondary outcomes were overall survival (OS), recurrent biliary obstruction (RBO), time to RBO (TRBO), technical and clinical success, and adverse events. Results A total of 73 patients were enrolled in this study. The non-obstruction rate at 6 months was 61%. The median OS and TRBO were 233 and 216 days, respectively. The technical and clinical success rates were 100% and 97%, respectively. Furthermore, the rate of occurrence of RBO and adverse events was 49% and 21%, respectively. The length of bile duct stenosis (<2.2 cm) was the only significant risk factor for stent migration. Conclusions The non-obstruction rate of a novel fully covered SEMS for MDBO is comparable to that reported earlier but shorter than expected. Short bile duct stenosis is a significant risk factor for stent migration

コレステロール負荷時におけるキノア蛋白質のコレステロール上昇抑制効果

キノアより蛋白質画分(QPro)を取得した。マウスに0.5%コレステロールを含む食餌を基本とし,これにQProを0%(コントロール群),2.5%および5.0%添加(QPro添加群)して4週間経口投与した。QPro添加群とコントロール群間で食事摂取量,体重増加に有意差を認めなかった。QPro添加群では血清と肝臓の総コレステロールの上昇を有意に抑制した。QPro添加群の糞中胆汁酸量は14日目でコントロール群に比べ増加した。肝臓におけるHMG-CoA reductaseの発現は,コントロール群に比べQPro添加群で有意に減少した。これらの結果より,キノア蛋白質画分の血清および肝臓コレステロールの上昇抑制作用は,糞中への胆汁酸排泄の促進およびコレステロール合成系酵素の抑制にあると推察した。We extracted protein fraction (QPro) from quinoa seeds. Mice were fed on 0.5% cholesterol diet, containing 0% (control), 2.5% and 5.0% of QPro respectively (2.5% QPro and 5.0% QPro) for 4 weeks. Neither of the diets with additional QPro showed a significant difference between food intake and body weight gain. The QPro additional diet significantly prevented the increase in plasma and liver total cholesterol levels. Excretion of bile acids in the QPro groups was higher than in the control group by the 14th day. Expression of mRNA of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver, a key enzyme for cholesterol biosynthesis, was suppressed by the QPro diet. These results suggest that the prevention of increases in plasma and liver cholesterol levels in mice fed the QPro diet can be ascribed to the promotion of fecal excretion of bile acid and to suppress the expression of the cholesterol synthesis enzyme

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Clusters of coronavirus disease 2019 in medical institutions and elderly care facilities in Okayama Prefecture

　Coronavirus disease 2019 has spread worldwide and has yet to be contained. The Japanese government has taken measures against the occurrence of clusters. However, there has little evaluation of the occurrence of the clusters and their changes. Therefore, we investigated the occurrence of the clusters in medical institutions and elderly care facilities in Okayama Prefecture. 　We compared the characteristics of the clusters that occurred in each of the wave between October 21, 2020, and September 30, 2021, by using the data published that interval. As a case study, we also evaluated the characteristics of positive patients at a medical institution over where a cluster occurred in case the fourth wave. 　The overall number of cluster outbreaks decreased with the spread of vaccination. In the fourth wave, there was a period in which the vaccination of staff members at medical institutions became widespread, while patients or facility users were unvaccinated, resulting in a longer convergence period and an increase in the number of positive cases among patients relative to the number of staff members. 　The impact of the spread of vaccination and the duration of immunity acquired after vaccination on the occurrence of clusters should be closely monitored in the future