Perceptions and attitudes of users and non-users of mental health services concerning mental illness and services in Japan

ObjectivesThere is a global movement to develop and implement community-based integrated mental health systems. The present study attempted to clarify the perceptions and attitudes of users and non-users of mental health services concerning mental illness and services in Japan.MethodsA new questionnaire was developed for this internet survey. Data from 500 outpatients with depression and 500 healthy subjects were sampled according to the demographics of the Japanese population.ResultsOver 90% of healthy subjects and over 70% of patients were unaware of the common age of onset or lifetime prevalence of mental illness. Over 90% of the healthy subjects and about 70% of the patients could not describe any services where they would feel comfortable discussing mental health problems. In both groups, “adolescents and young adults” were ranked first as a target population for mental health and illness policies. The top requirement for the integrated care systems was the promotion and awareness of correct knowledge of mental illness in both the healthy subjects and patients.ConclusionSocietal requirements could include disseminating correct knowledge, awareness-raising actions for society, and implementing services where people, especially young people, can easily consult and receive support in the community

A patient with esophageal hemangioma treated by endoscopic mucosal resection : a case report and review of the literature

In a 58-year-old male, upper digestive endoscopy revealed a protruding lesion in the esophagus on a medical examination. The patient was referred to the Department of Surgery in our hospital to undergo surgery. On the initial consultation, upper digestive endoscopy showed a smooth, soft, black purple, typeⅡprotruding lesion measuring approximately 25mmat 35 cm apart from the incisor. For diagnotic treatment and patient’s request, endoscopic mucosal resection (EMR)was performed. The resected specimen measured 25mm× 25 mm. The histological findings suggested cavernous hemangioma. To treat esophageal hemangioma, esohagectomy, tumor enucleation, or sclerotherapy has been performed. However, recently, thorough preoperative examination, such as endoscopic ultrasonography (EUS), has facilitated endoscopic resection, such as EMR

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

Biogeochemistry and limnology in Antarctic subglacial weathering: molecular evidence of the linkage between subglacial silica input and primary producers in a perennially ice-covered lake

We report a 6,000 years record of subglacial weathering and biogeochemical processes in two perennially ice-covered glacial lakes at Rundvagshetta, on the Soya Coast of Lutzow-Holm Bay, East Antarctica. The two lakes, Lake Maruwan Oike and Lake Maruwan-minami, are located in a channel that drains subglacial water from the base of the East Antarctic ice sheet. Greenish-grayish organic-rich laminations in sediment cores from the lakes indicate continuous primary production affected by the inflow of subglacial meltwater containing relict carbon, nitrogen, sulfur, and other essential nutrients. Biogenic silica, amorphous hydrated silica, and DNA-based molecular signatures of sedimentary facies indicate that diatom assemblages are the dominant primary producers, supported by the input of inorganic silicon (Si) from the subglacial inflow. This study highlights the significance of subglacial water-rock interactions during physical and chemical weathering processes and the importance of such interactions for the supply of bioavailable nutrients

A case of alpha-fetoprotein-positive thymic small cell carcinoma: a case report

Abstract Background An alpha-fetoprotein (AFP)-positive neuroendocrine tumor of the thymus is a rare thoracic malignancy. Few cases of AFP-positive thymic large cell neuroendocrine carcinoma have been reported, with no known previous report of an AFP-positive thymic small cell carcinoma. We encountered a patient with an AFP-positive small cell carcinoma and report here the clinical course. Case presentation A 40-year-old man was transferred to our hospital for a large anterior mediastinal tumor and showed an elevated serum AFP level. Computed tomography-guided biopsy results led to diagnosis of small cell carcinoma. Induction chemoradiotherapy was performed before surgery because of pulmonary artery invasion. The response to Induction chemoradiotherapy varied among sites, with the main tumor showing shrinkage and the metastasis site growth. This discrepancy suggested a histologic type unresponsive to or cancer cells potentially resistant to chemotherapy, thus a surgical re-biopsy was performed and histological findings revealed AFP-positive small cell carcinoma. Additional chemotherapy was performed, though could not control cancer progression, and the patient died 8 months after the first medical examination. Conclusions Our present clinical experience indicates the importance of histological examination for determining AFP-positive anterior mediastinal tumor treatment. Although AFP-positive neuroendocrine tumor of the thymus is relatively rarer than germ cell carcinoma, differential diagnosis with use of a histological examination should be considered because of the potentially poorer prognosis. The present clinical findings for an AFP-positive neuroendocrine tumor of the thymus case are considered useful for establishing an optimal treatment strategy in the future

Therapeutic Targeting of Cancer-Associated Fibroblasts in the Non-Small Cell Lung Cancer Tumor Microenvironment

Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. The most common lung cancer is non-small cell lung cancer (NSCLC), with an overall 5-year survival rate of around 20% because NSCLC is a metastatic disease. A better understanding of the mechanism underlying lung cancer metastasis is therefore urgently needed. The tumor microenvironment involves different types of stromal cells and functions as key components in the progression of NSCLC. Through epithelial–mesenchymal transition (EMT), in which epithelial cells lose their polarity and acquire mesenchymal potential, cancer cells acquire metastatic abilities, as well as cancer stem-cell-like potential. We previously reported that cancer-associated fibroblasts (CAFs) interact with lung cancer cells to allow for the acquisition of malignancy and treatment resistance by paracrine loops via EMT signals in the tumor microenvironment. Furthermore, CAFs regulate the cytotoxic activity of immune cells via various cytokines and chemokines, creating a microenvironment of immune tolerance. Regulation of CAFs can therefore affect immune responses. Recent research has shown several roles of CAFs in NSCLC tumorigenesis, owing to their heterogeneity, so molecular markers of CAFs should be elucidated to better classify tumor-promoting subtypes and facilitate the establishment of CAF-specific targeted therapies. CAF-targeted cancer treatments may suppress EMT and regulate the niche of cancer stem cells and the immunosuppressive network and thus may prove useful for NSCLC treatment through multiple mechanisms