Undifferentiated Sarcoma of the Salivary Gland in a Mongolian Gerbil (Meriones unguiculatus)

A subcutaneous mass was found in the lower ventral neck region of a 55-week-old male Mongolian gerbil (Meriones unguiculatus). Histopathologically, the mass involved salivary glands and featured diffuse proliferation of pleomorphic neoplastic cells with large necrotic foci. The lesion was well demarcated from the surrounding tissue, although invasive growth to fibrous septa was occasionally observed. The neoplastic cells were mainly arranged in irregular sheets with severe cellular atypia, round to oval nuclei and varying amounts of eosinophilic cytoplasm. Mitotic figures and multinucleated giant cells were frequent. Immunohistochemical analysis revealed that the neoplastic cells were strongly positive for vimentin and S-100 and negative for NSE, cytokeratin, α-SMA, c-kit, factor VIII, CD34, α-1-antitrypsin, lysozyme and MSR-A. Based on the results, the mass was diagnosed as an undifferentiated sarcoma of the salivary gland. To the best of our knowledge, this is the first report of such a tumor in Mongolian gerbils

Mortality risk associated with nuclear disasters depends on the time during and following evacuation of hospitals near nuclear power plants: An observational and qualitative study

This study aimed to examine the factors correlated with emergency evacuations on patients’ prognosis in hospitals severely affected by the Fukushima Daiichi nuclear power plant (FDNPP) accident in March 2011, and to recommend measures mitigating potential health risks among them in future disasters. Seven hospitals within a 20-km radius of the FDNPP were designated as the evacuation zone, of which three hospitals located within a 5-km radius were examined. Information regarding hospital emergency evacuation among the three hospitals from previous literature and official reports were integrated and interview outcomes of staff at each hospital were qualitatively analyzed using thematic analysis. Our thematic analysis identified four themes: insufficient preparedness for disaster, difficulty of patient evacuation, insufficient materials, and insufficient information. Comparison of the three hospitals located within a 5-km radius of the FDNPP revealed that hospitals with several patients or those with a high proportion of bedridden or critically ill patients faced more difficulty in emergency evacuation and experienced higher fatalities. In addition to individual evacuation plans, for future preparedness, external and public organizations should prepare disaster responses such as procedures to integrate information on the status of each medical facility and measures to support them individually

Phylogenic study on Ephedra plants related to Ephedra sinica by sequence analysis of the internal transcribed spacer 2 region (ITS2) in nuclear ribosomal DNA

古来よりマオウ属植物は、日本及び中国で生薬として用いられており、中国のEphedra 属植物の系統は3つの大きなグループに分かれている。現在、Ephedra sinica が日本及び中国市場で優位を占めている。E.sinica は、東および中央アジアに分布するE. dahurica やE. pseudodistachya と、形態的に類似している。一方西アジア及びヨーロッパに分布するマオウ属植物であるE. lomatolepis や E. distachya との近縁性は、議論のあるところである。新たな生薬資源の探索の一環として、今回E. sinica およびその近縁植物について、internal transcribed spacer 2 (ITS2) の塩基配列を分析および系統解析を行い、以下の結果を得た。(1)極東ロシア(ブリアチアおよびチタ)のE. dahurica 検体のITS2 塩基配列は、中国及びモンゴル産E. sinica とほぼ同一であり、この2種は同種と考えられた。(2)中央アジア産のE. pseudodistachya と E. lomatolepis検体は、E. sinica/ E. dahuricaと緩やかなクラスターを形成し、近縁性が示唆された。( 3)西アジア及びヨーロッパ産のE. distachya 検体は、E. sinica / E. dahurica とは系統的に異なっていた。In East Asia, the aerial part of Ephedra plants has been staple crude drug from ancient times. Among them, crude drug derived from E. sinica is considered to be the most widely distributed in both Chinese and Japanese markets. E. sinica has herbaceous appearance and belongs to one of 3 phyletic groups of Chinese Ephedra plants. In morphological respect, E. sinica is very similar to E. dahurica, and the Central Asian species E. pseudodistachya, On the other hand, delimitation of E. lomatolepis as well as from the European/West Asian E. distachya is controversial. Aiming to develop new Ephedra plant resources and evaluate them as crude drug, the genetic relationship was examined using ITS 2 sequences of an extended sampling from West Europe to East Asia. As the result, following findings were made: (1) specimens of E. sinica from China and Mongolia were almost identical to those of E. dahurica from southern Buryatia and Chita. (2) Each of E. pseudodistachya and E. lomatolepis specimens from West to Central Asia formed a loose cluster with E. sinica and E. dahurica. (3) Specimens of E. distachya from West Asia to Europe grouped together. The results confirmed the result obtained from ITS1 analysis as well as hypothesis based on morphology that E. sinica and E. dahurica should be merged under the same name

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

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

Japanese adolescents' self-concept and well-being in comparison with other countries

Background: In a rapidly changing and increasingly interconnected world, the issue of mental health and well-being among adolescents is one of the important research topics. However, there have been few studies amongst Japanese adolescents that have been published in international journals. Objectives: (I) to make a comparison in selfconcept between healthy adolescents in Japan and Sweden, (II) to address the influence of perceived parental rearing on self-concept and mental health problems among Japanese adolescents, (III) to investigate contributions of attachment and self-concept to mental health problems reported by Japanese adolescents, (IV) to address a comparison of mental health problems and self reported competence in adolescents from Greece, Japan, Russia, and Sweden. Methods: The following self-report instruments were used: Self- Description Questionnaire II (Marsh, 1992), Actual-Ideal Questionnaire (Nishikawa, 2003), Self-Description Questionnaire IIShort (Marsh, Ellis, Parada, Richards, & Heubeck, 2005), Youth Self- Report (Achenbach, 1991), Attachment Questionnaire- for Children (Sharpe et al., 1998), and Egna Minnen Beträffande Uppfostran (my memories of child upbringing) for Children (Muris, Meesters, & van Brakel, 2003). The participants for Paper I were adolescents aged 14 and 15 from Japan (n=144) and Sweden (n=96). One hundred ninety three Japanese students between the ages of 15-19 participated in Paper II and 228 students for Paper III. The participants for Paper IV were 812 healthy adolescents between 15 and 17 years of age from Greece (n=152), Japan (n=219), Russia (n=159), and Sweden (n=282).  Results: Paper I showed that Japanese students reported less positive self-concept compared to the Swedish counterparts. The results were discussed in terms of different response style and modesty in Japanese culture. Paper II showed that dysfunctional parental rearing and insecure peer attachment were associated with negative self-concept and more mental health problems. A unique influence on mental health problems from parent-adolescent relationships depending on the gender of parents and adolescents was also found. Paper III showed a mediating role of self-concept in influencing the relationships between attachment style and Internalizing Problems. Paper IV indicated rather small differences across countries in the syndrome scales. Japanese and Swedish adolescents tended to score lower than Russian and Greek counterparts. Some cultural specific syndromes were found. Conclusion: These results reported in this thesis present a general view of Japanese adolescents’ self-concept and the influence of interpersonal relationships in mental health problems assessed by Western self-report instruments. When being compared with other countries, cultural background and response style must be taken into account

Type and Timing of Negative Life Events Are Associated with Adolescent Depression

Previous studies have demonstrated an association between negative life events (NLEs) in childhood and resilience/posttraumatic growth (PTG) with regard to the pathogenesis of major depressive disorder. We hypothesized that the type and timing of NLEs interact to influence mental health in the general youth population. Therefore, the present study aimed to examine the effects of NLE timing and intensity on current depressive symptoms, and to determine the direct and indirect effects of NLEs/resilience on PTG and depression among non-clinical adolescents. Data were collected from 1,038 high-school students across seven high schools in Fukui, Japan, during their freshman and sophomore years (648 boys and 390 girls, mean age = 15.71, SD = 0.524). Respondents completed a set of questionnaires designed to evaluate the type and timing of NLEs, depressive and traumatic symptoms, and PTG. Cluster analysis was used to divide participants into three groups based on outcomes: “cluster 1” (n = 631), for whom depressive scores were significantly lower than other two subgroups (p < 0.05, for both); “cluster 2” (n = 52), for whom levels of current and past perceived stress associated with NLEs were significantly higher than those of the other two subgroups (p < 0.05, for both); “cluster 3” (n = 374), for whom perceived stress at the time of NLE was significantly higher than that of participants in the cluster 1 (p < 0.05) group, but not the cluster 2 group. Our findings indicated that exposure to NLEs at a younger age resulted in stronger negative outcomes and that NLE timing and intensity were associated with PTG and current symptoms of depression. Furthermore, path analysis demonstrated that associations between perceived stress at the time of NLEs were direct and indirect predictors of current depression via PTG and that posttraumatic stress symptom and PTG mediate the association between NLEs/trait-resiliency and current depression. In conclusion, our findings suggest that event intensity, NLE timing, and gender may play a role in emotional vulnerability during adolescence

Long-Term Outcomes after Switching to Tenofovir Alafenamide in Patients with Chronic Hepatitis B

We sought to determine the long-term outcomes of chronic hepatitis B (CHB) cases switching to tenofovir alafenamide (TAF, n = 104, median age = 63.5 years). Data at switching to TAF (baseline) and those at 1, 2, 3, 4, and 5 years from switching to TAF were compared. At baseline, HB envelop antigen (HBeAg) seropositivity was found in 20 patients (19.2%), and undetectable HBV-DNA in 77 patients (74.0%). Percentage of detectable HBV-DNA significantly reduced at any time point. HB surface antigen (HBsAg) levels significantly reduced at 3, 4, and 5 years. The percentage of HBeAg seropositivity significantly reduced at 5 years. HB core related antigen levels did not significantly change. In patients with baseline HbeAg seropositivity, HbsAg levels significantly reduced at any time point, and a similar trend was found in patients without HBeAg seropositivity. In patients with baseline FIB4 index >1.85, HBsAg levels significantly reduced at 3, 4, and 5 years, and in patients with baseline FIB4 index <1.85, HBsAg levels significantly reduced at any time point. The estimated glomerular filtration rate significantly reduced only at 5 years. The discontinuation rate owing to the side effects of TAF was 0%. In conclusion, switching to TAF therapy in patients with CHB may be effective and safe at least up to 5 years

Differences and Similarities of Mental Health Problems Reported by Adolescents : From Greece, Japan, Russia, and Sweden

The aims of the present study were to: 1) compare scores and scales of the Youth Self-Report (YSR) reported by healthy adolescents 15 - 17 years of age from Greece, Japan, Russia, and Sweden, 2) analyze gender and age effects of the YSR syndrome scores between and within countries, and 3) compare scores of competence scales and their associations to mental health problems. A comparison of problems (n = 812) yields a small effect size of 4.8% for cross-country in YSR total problems scores. There was a deviation above the overall mean for Greece and Russia, while Sweden and Japan had deviations below the mean. The effect sizes of country for narrowband and broadband scales were small or medium. Analysis within and between countries pointed out some problems that might be more/less common in some countries than others. In their total competence score, Greek adolescents scored higher than Swedish or Japanese. There were some negative associations between syndrome and competence scales across countries. Gender differences were shown across the countries with the exception of Japan. Age differences were less consistent due to the small range of age groups. Even though YSR is used in all four countries, translations and sampling procedure may influence (be one of) the variations