Evaluation of FilmArray respiratory panel multiplex polymerase chain reaction assay for detection of pathogens in adult outpatients with acute respiratory tract infection

Although viruses are the major pathogen that causes upper respiratory tract infection (URTI) and acute bronchitis, antibiotics have been prescribed. This was a prospective observational study in influenza epidemics that enrolled adult outpatients who visited a hospital with respiratory tract infection symptoms. In this study, we evaluated the usefulness of FilmArray respiratory panel (RP). Fifty patients were enrolled. FilmArray RP detected the pathogens in 28 patients. The common pathogens were influenza virus (n = 14), respiratory syncytial virus (n = 6), and human rhinovirus (n = 6). Of the 14 patients with influenza virus, 6 were negative for the antigen test. The physicians diagnosed and treated the patients without the result of FilmArray in this study. Of the patients with positive FilmArray RP, 9 were treated with antibiotics; however, bacteria were detected in only 3 patients. By implementing FilmArray RP, URTI and acute bronchitis would be precisely diagnosed, and inappropriate use of antibiotics can be reduced

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

Re-infection of T. gondii after HSCT

Toxoplasma gondii (T.gondii) reactivation is one of the fatal complications after hematopoietic stem cell transplantation (HSCT); however, re-infection has not been reported. Here, we report a case of mycosis fungoides in which cervical lymphadenopathy developed after HSCT. Initially, recurrent lymphoma was suspected. However, biopsy of the lymph node showed typical histology of toxoplasmosis and serology showed re-infection of T.gondii. Toxoplasmosis needs to be differentiated for cases with lymphoadenopthy after HSCT

Chronic subdural hematoma with persistent hiccups: A case report

Supratentorial hiccup is a rare condition and no patients with persistent hiccups and chronic subdural hematoma have been reported. A 38-year-old man with intractable hiccups, headache, and nausea was admitted to our hospital. Computed tomography revealed a supratentorial chronic subdural hematoma on the left side. After burr hole surgery to remove the hematoma his hiccups disappeared immediately and he was discharged home on the 3rd postoperative day with no neurological deficits. Although the role of the supratentorial nervous system in hiccups is not clearly understood, supratentorial areas play an important role in the stimulation or suppression of the hiccup centers. Chronic hiccups may be a presenting symptom of chronic subdural hematoma attending headache with nausea if it has no gastrointestinal abnormality

Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia

Intragenic deletion of IKZF1 is a recurrent genomic alteration in acute lymphoblastic leukemia. The deletions are mediated by illegitimate variable(diversity)joining recombination via cryptic recombination signal sequences (RSSs). We developed a fluorescence in situ hybridization (FISH) probe set that can detect any type of IKZF1 deletion, including the commonly deleted exon 4 to 7 region. The probe set consists of a designed probe for the commonly deleted region (Cy3; red) and a bacterial artificial chromosomes clone probe for detecting the 3' flanking region (Spectrum Green). Intact IKZF1 showed a fusion signal, and the deleted allele showed loss of the red signal (0R1G1F). The FISH probes worked correctly for human leukemic cell lines and clinical samples. One case showed an atypical break-apart signal (1R1G1F). Inverse PCR of the case revealed rearrangement of the excised IKZF1 fragment into a legitimate RSS site at Ig κ on chromosome 2, suggesting a pathogenic role of this recombination-activating gene 1/2-mediated event. In this study, we established FISH probe detecting IKZF1 deletion in a quick, quantitative, and cost-effective manner, and the results provided a novel insight into B-cell receptor editing by rearrangement of a cryptic RSS-mediated genomic fragment in acute lymphoblastic leukemia pathology

Variabilitas Angin Berdasarkan Pengamatan Radar Boundary Layer 1357.5 Mhz Di Serpong

Analisa spektral data angin hasil pengamatan Boundary Layer Radar di Serpong menunjukkan adanya variasi harian, empat harian, 30 - 60 harian dan tahunan. Variasi harian berkaitan dengan adanya sirkulasi darat-laut, variasi 4 (empat) harian berkaitan dengan gangguan gelombang Rossby -gravity, variasi 30 - 60 harian berkaitan dengan gelombang Kelvin dan variasi tahunan berkaitan dengan pergantian antara angin musim samudera Hindia dan angin pasat samudera Pasifik.Hlm. 44-5

Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia : A Hokkaido Leukemia Net Study

The association between Wilms tumor 1 (WT1) expression, genetic abnormalities and homozygous single polymorphism (SNP) in WT1 gene was evaluated in 252 acute myelogenous leukemia (AML) patients. WT1 expression correlated with prognostic genetic abnormalities. Homozygous WT1 SNP rs16754 was associated with lower expression of WT1. WT1 expression had no prognostic impact in any cytogenetic group or SNP status. Background: The prognostic impact of WT1 expression at diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of this study was to determine the correlations of WT1 expression at diagnosis of AML with established prognostic alterations. Patients and Methods: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, SNP in WT1 gene (rs16754), and Flt3-ITD mutation were analyzed for all patients. NPM1 mutation and CEBPA double mutation were analyzed for cytogenetically normal (CN)-AML. KIT mutation was analyzed for core-binding factor (CBF)-AML. Results: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly higher than that in AML with t(8;21). In cases with CN-AML, Flt3-ITD and NPM1 mutations were both correlated with higher expression of WT1, whereas CEBPA double mutation was related to lower WT1 expression. The existence of both Flt3- ITD and NPM1 mutations showed synergistically higher expression of WT1 in CN-AML. SNP in WT1 gene (rs16754) was significantly associated with lower expression of WT1. WT1 levels were not prognostic factors in the total cohort, in any cytogenetic group nor SNP status. Conclusion: Since WT1 expression correlated to known prognostic factors, the prognostic impact of WT1 levels might be misunderstood depending on the distribution of collaborative mutations in each cohort. We conclude that the prognostic significance of WT1 at diagnosis of AML is weak compared to other established prognostic factors