Visualization of Cerebrospinal Fluid Outflow and Egress along the Nerve Roots of the Lumbar Spine.

Intrinsic cerebrospinal fluid (CSF) dynamics in the brain have been extensively studied, particularly the egress sites of tagged intrinsic CSF in the meninges. Although spinal CSF recirculates within the central nervous system (CNS), we hypothesized that CSF outflows from the lumbar spinal canal. We aimed to visualize and semi-quantify the outflow using non-contrast MRI techniques. We utilized a 3 Tesla clinical MRI with a 16-channel spine coil, employing time-spatial labeling inversion (Time-SLIP) with tag-on and tag-off acquisitions, T2-weighted coronal 2D fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal 3D centric ky-kz single-shot FSE (cSSFSE). Images were acquired using time-spatial labeling inversion pulse (Time-SLIP) with tag-on and tag-off acquisitions with varying TI periods. Ten healthy volunteers with no known spinal diseases participated. Variations in tagged CSF outflow were observed across different thoracolumbar nerve root segments in all participants. We quantified CSF outflow at all lumbar levels and the psoas region. There was no significant difference among the ROIs for signal intensity. The tagged CSF outflow from the spinal canal is small but demonstrates egress to surrounding tissues. This finding may pave the way for exploring intrathecal drug delivery, understanding of CSF-related pathologies and its potential as a biomarker for peripheral neuropathy and radiculopathy

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

Lung parenchymal signal intensity in MRI: A technical review with educational aspirations regarding reversible versus irreversible transverse relaxation effects in common pulse sequences

Lung parenchyma is challenging to image with proton MRI. The large air space results in ~l/5th as many signal-generating protons compared to other organs. Air/tissue magnetic susceptibility differences lead to strong magnetic field gradients throughout the lungs and to broad frequency distributions, much broader than within other organs. Such distributions have been the subject of experimental and theoretical analyses which may reveal aspects of lung microarchitecture useful for diagnosis. Their most immediate relevance to current imaging practice is to cause rapid signal decays, commonly discussed in terms of short T2* values of 1 ms or lower at typical imaging field strengths. Herein we provide a brief review of previous studies describing and interpreting proton lung spectra. We then link these broad frequency distributions to rapid signal decays, though not necessarily the exponential decays generally used to define T2* values. We examine how these decays influence observed signal intensities and spatial mapping features associated with the most prominent torso imaging sequences, including spoiled gradient and spin echo sequences. Effects of imperfect refocusing pulses on the multiple echo signal decays in single shot fast spin echo (SSFSE) sequences and effects of broad frequency distributions on balanced steady state free precession (bSSFP) sequence signal intensities are also provided. The theoretical analyses are based on the concept of explicitly separating the effects of reversible and irreversible transverse relaxation processes, thus providing a somewhat novel and more general framework from which to estimate lung signal intensity behavior in modern imaging practice

Current status of gastrectomy and reconstruction types for patients with proximal gastric cancer in Japan

Background: Surgical procedures for proximal gastric cancer remain a highly debated topic. Total gastrectomy (TG) is widely accepted as a standard radical surgery. However, subtotal esophagectomy, proximal gastrectomy (PG) or even subtotal gastrectomy, when a small upper portion of the stomach can technically be preserved, are alternatives in current clinical practice. Methods: Using a cohort of the PGSAS NEXT trial, consisting of 1909 patients responding to a questionnaire sent to 70 institutions between July 2018 and December 2019, gastrectomy type, reconstruction method, and furthermore the remnant stomach size and the anti-reflux procedures for PG were evaluated. Results: TG was the procedure most commonly performed (63.0%), followed by PG (33.4%). Roux-en-Y was preferentially employed following TG irrespective of esophageal tumor invasion, while jejunal pouch was adopted in 8.5% of cases with an abdominal esophageal stump. Esophagogastrostomy was most commonly selected after PG, followed by the double-tract method. The former was preferentially employed for larger remnant stomachs (≧3/4), while being used slightly less often for tumors with as compared to those without esophageal invasion in cases with a remnant stomach 2/3 the size of the original stomach. Application of the double-tract method gradually increased as the remnant stomach size decreased. Anti-reflux procedures following esophagogastrostomy varied markedly. Conclusions: TG is the mainstream and PG remains an alternative in current Japanese clinical practice for proximal gastric cancer. Remnant stomach size and esophageal stump location appear to influence the choice of reconstruction method following PG

Quantification of edematous changes by diffusion magnetic resonance imaging in gastrocnemius muscles after spinal nerve ligation

Using a rat spinal nerve ligation-induced CRPS model, we show that edematous changes in gastrocnemius muscle can be detected quantitatively by diffusion magnetic resonance imaging (MRI). Using the line-scan diffusion spectrum on a 1.5 T clinical MR imager, we demonstrate significant elevation of the apparent diffusion coefficient (ADC) ratios in gastrocnemius muscle on the ligated versus the sham-operated rats by one day after surgery, those ratios gradually decreased over time. Meanwhile, T2 ratios in gastrocnemius muscle on the ligated rats increased gradually and significantly, peaking two weeks after surgery, and those ratios remained high and were consistent with edema. Expression of vascular endothelial growth factor (VEGF), a key regulator of blood vessel formation and function, was significantly lower in gastrocnemius muscle on the ligated versus non-ligated side, suggesting that nerve ligation promotes edematous changes and perturbs VEGF expression in target muscle