Psycho-Physiological Response by 3D Image and Sound

AbstractRecently, advances in stereoscopic imaging technology have opened up opportunities to view three-dimensional (3D) images and it is expected that 3D imaging technology will be further utilized in medical facilities. In our study, we investigated the psycho-physiological effects induced by 3D imagery and sound combinations by using functional near infrared spectroscopy (fNIRS), electrocardiograms (ECG), and the Roken Arousal Scale (RAS). The following four image and sound conditions were compared under both 2D and 3D conditions: sound only, image only, synchronized image and sound combinations, and asynchronized image and sound combinations. In all tests, brain activity in the frontal cortex was measured by placing NIRS probes near the prefrontal cortex and in the vicinity of dorsolateral area 46. To evaluate any increase or decrease in oxygenated hemoglobin (oxyHb), we used δoxyHb. Briefly, oxyHb waveform data are passed through a differential filter, after which a sum of more than zero is defined as a positive component, and a sum less than zero is defined as a negative component. The δoxyHb value is defined as the positive component minus the negative component. It was found that δoxyHb values for sound and imagery alone under the 2D condition exceeded those under the corresponding 3D condition. Furthermore, δoxyHb values under synchronized and asynchronized 3D conditions were higher than those recorded under the corresponding 2D condition. These results suggest differences in brain activities between 2D and 3D imagery, or with or without sound. The highest δoxyHb value was recorded for 3D imagery with synchronized sound. High frequency component (HF) values for a synchronized image and sound under 3D conditions were the lowest, and low frequency component (LF) / HF values for the synchronized image and sound under 3D conditions were the highest. These results indicate the predominance of the sympathetic nervous system during sound-synchronized 3D imagery

Clinical Application of Coagulation Biomarkers

Coagulopathy is of intense interest in the fields of emergency medicine, with many recent studies of coagulation biomarkers for clinical use. The occurrence of disseminated intravascular coagulation (DIC) also resulted in the activation of studies about the coagulopathy. At present DIC has been admitted in many clinical conditions and many coagulation biomarkers have been studied. Fibrin degradation product (FDP) and D-dimer are one type of coagulation biomarker. A characteristic of FDP and D-dimer is the rapid and dynamic elevation of their levels when fibrinolysis occurs in several acute diseases. In this chapter, we present the clinical application of FDP and D-dimer. In trauma, FDP and -dimer have been used for the evaluation of trauma severity, to predict the likelihood of hemorrhage and to evaluate the need for the transfusion of packed red blood cells. In cardiac pulmonary arrest (CPA), FDP and D-dimer have been useful for predicting the return of spontaneous circulation. Thus, the measurement of coagulation biomarkers is useful in the diagnosis and/or treatment of trauma and CPA

Evaluation of contrast visual acuity in patients with retinitis pigmentosa

Kazumi Oomachi1, Kazuha Ogata2, Takeshi Sugawara2, Akira Hagiwara2, Akira Hata1, Shuichi Yamamoto21Department of Public Health; 2Department of Ophthalmology, Chiba University Graduate School of Medicine, Chiba, JapanBackground: The purpose of this study was to determine visual acuity at different contrast levels under photopic and mesopic conditions in patients with retinitis pigmentosa.Methods: Sixty eyes of 31 normal controls, 92 eyes of 52 patients with retinitis pigmentosa without other ocular disorders (RP-1 group), and 20 eyes of 14 patients with retinitis pigmentosa with cataracts and without other ocular disorders (RP-2 group) were studied. Conventional visual acuity was measured using a conventional Landolt ring chart with 100% contrast and luminance of 150 cd/m2. All of the patients with retinitis pigmentosa had a decimal visual acuity better than 1.0. Contrast visual acuity was measured with the same Landolt ring chart with contrasts of 100% and 10% and under photopic (200 cd/m2) and mesopic (10 cd/m2) conditions. Decimal visual acuities were converted to logMAR units for the analyses.Results: The 100% contrast visual acuity and the 10% contrast visual acuity determined under both photopic and mesopic conditions were significantly poorer in both the RP-1 and RP-2 groups than in the controls. The differences between the conventional visual acuity and the 100% contrast visual acuity were significantly greater in the RP-1 and RP-2 groups than in the controls under both photopic and mesopic conditions. The differences between the 100% contrast visual acuity and the 10% contrast visual acuity were not significant among the three groups under photopic and mesopic conditions.Conclusion: Contrast visual acuities were greatly reduced in patients with retinitis pigmentosa with relatively well preserved conventional visual acuity, and the contrast visual acuity was largely influenced by ambient light levels in patients with retinitis pigmentosa. Although a longitudinal study for confirmation has to be performed, our findings indicate that contrast visual acuity is a better test to follow changes in visual function in patients with retinitis pigmentosa.Keywords: retinitis pigmentosa, contrast visual acuity, photopic vision, mesopic visio

Interferon signaling and hypercytokinemia-related gene expression in the blood of antidepressant non-responders

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant responsiveness using a novel data-driven approach based on statistical pattern recognition. We retrospectively divided patients with major depressive disorder into antidepressant responder and non-responder groups. Comprehensive gene expression analysis was performed using peripheral blood without narrowing the genes. We designed a classifier according to our own discrete Bayes decision rule that can handle categorical data. Nineteen genes showed differential expression in the antidepressant non-responder group (n = 15) compared to the antidepressant responder group (n = 15). In the training sample of 30 individuals, eight candidate genes had significantly altered expression according to quantitative real-time polymerase chain reaction. The expression of these genes was examined in an independent test sample of antidepressant responders (n = 22) and non-responders (n = 12). Using the discrete Bayes classifier with the HERC5, IFI6, and IFI44 genes identified in the training set yielded 85% discrimination accuracy for antidepressant responsiveness in the 34 test samples. Pathway analysis of the RNA sequencing data for antidepressant responsiveness identified that hypercytokinemia- and interferon-related genes were increased in non-responders. Disease and biofunction analysis identified changes in genes related to inflammatory and infectious diseases, including coronavirus disease. These results strongly suggest an association between antidepressant responsiveness and inflammation, which may be useful for future treatment strategies for depression

IMiD/CELMoD-induced growth suppression of adult T-cell leukemia/lymphoma cells via cereblon through downregulation of target proteins and their downstream effectors

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasia associated with human T-cell leukemia virus type 1 (HTLV-1) infection and has an extremely poor prognosis. Lenalidomide (LEN; a second-generation immunomodulatory drug [IMiD]) has been employed as an additional therapeutic option for ATL since 2017, but its mechanism of action has not been fully proven, and recent studies reported emerging concerns about the development of second primary malignancies in patients treated with long-term IMiD therapy. Our purpose in this study was to elucidate the IMiD-mediated anti-ATL mechanisms. Thirteen ATL-related cell lines were divided into LEN-sensitive or LEN-resistant groups. CRBN knockdown (KD) led to a loss of LEN efficacy and IKZF2-KD-induced LEN efficacy in resistant cells. DNA microarray analysis demonstrated distinct transcriptional alteration after LEN treatment between LEN-sensitive and LEN-resistant ATL cell lines. Oral treatment of LEN for ATL cell-transplanted severe combined immunodeficiency (SCID) mice also indicated clear suppressive effects on tumor growth. Finally, a novel cereblon modulator (CELMoD), iberdomide (IBE), exhibited a broader and deeper spectrum of growth suppression to ATL cells with efficient IKZF2 degradation, which was not observed in other IMiD treatments. Based on these findings, our study strongly supports the novel therapeutic advantages of IBE against aggressive and relapsed ATL

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

Variation in the utilization of angioembolization for splenic injury in hospitals: a nationwide cross‐sectional study in Japan

Aim Substantial variations in the utilization of angioembolization have been reported internationally. However, the existence of variations in the utilization of angioembolization in Japan is currently unknown. Methods This was a cross‐sectional study using data from a nationwide trauma registry in Japan. Of the 4,896 registered adult patients with splenic injury, we investigated 3,319 patients in the top 25% of the hospitals that registered the highest number of splenic injury patients in the Japan Trauma Data Bank. The primary outcome of this study was initial angioembolization. We calculated the expected initial angioembolization rates using multiple regression analysis adjusted for patient factors. In addition, we evaluated the range of observed‐to‐expected initial splenic angioembolization ratio for each hospital. Moreover, we assessed whether this ratio was increased with time. Results The frequency of initial splenic angioembolization ranged from 0% to 52%. The median expected initial angioembolization rate, calculated through multiple logistic regression analysis, was 19.7%. The observed‐to‐expected initial splenic angioembolization ratio for each hospital ranged from 0 to 2.36. The observed initial angioembolization rate tended to increase with time (P < 0.001). Conclusions Despite adjustment for patient factors, substantial variations were observed in the utilization of splenic angioembolization among hospitals in Japan