Technical Notes on Endoscopic Transnasal Transsphenoidal Approach for Clival Chondrosarcoma

Although there are various operative approaches for clival tumors, a transsphenoidal approach is one of choices when the main tumor extention is in an anterior-posterior direction with a slight lateral extension. However, this approach sometimes provides only narrow and deep operative field. Recently, endoscopic transnasal transsphenoidal approach is quite an effective approach for clival tumors because of the improvement of surgical instruments, image guidance systems, and techniques and materials of wound closure. In this paper, we describe the effectiveness, technical problems, and solution of this approach based on our experiences with two clival chondrosarcomas that was removed by endoscopic transnasal transsphenoidal approach

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

Endoscopic hematoma evacuation through dilated burr hole for acute subdural hematoma in elderly patients_ Feasibility of endoscopic procedure and its technical tips as less invasive surgery

Object: We describe results of endoscopic surgery for acute subdural hematoma in elderly patients, and simple technique of the endoscopic procedure for acute subdural hematoma (ASDH) through an extended burr hole in elderly patients and discuss its technical aspects. Methods: We performed endoscopic evacuation of acute subdural hematoma in selected fifteen elderly patients. The following data were collected and evaluated: age, sex, laterality, administration of anti-thrombotic agents, injury severity score (ISS), pre and post-operative GCS, modified Rankin scale (mRS) before and post-treatment of ASDH, type of anesthesia, operation time, origin of bleeding. Results: Postoperatively, satisfactory hematoma evacuation was accomplished. No hemorrhagic adverse effects related with endoscopic procedure were observed. Postoperative GCS was improved in all patients, and three patients were discharged with mRS 0–2 consistent with independent gait. Conclusion: Endoscopic evacuation of acute subdural hematoma for elderly patient is a less invasive treatment and might be technically feasible in selected cases

Metabolism of Acetate in Atherosclerosis

Introduction: Detection of vulnerable plaques is critically important for the selection of appropriate treatment and/or the prevention of atherosclerosis and ensuing cardiovascular diseases. In order to clarify the utility of [11C]acetate for atherosclerosis imaging, we determined the uptake and metabolism of acetate by in vitro studies using rabbit atherosclerotic arteries and [14C]acetate. Methods: Rabbits were fed with a conventional (n = 5) or a 0.5% cholesterol diet (n = 6). One side of the iliac-femoral arteries was injured by a balloon catheter. Radioactivity levels in the iliac-femoral arteries were measured after incubation in DMEM containing [1-14C]acetate for 60 min (% dpm/mg tissue). Radioactive components in the homogenized arteries were partitioned into aqueous, organic, and residue fractions by the Folch method, and analyzed by thin-layer chromatography (TLC). Results: The radioactivity level in the injured arteries of rabbits fed with the 0.5% cholesterol diet (atherosclerotic arteries) was significantly higher than that in either the non-injured or injured arteries of rabbits fed with the conventional diet (p < 0.05) (% dpm/mg tissue: conventional diet groups; 0.022 ± 0.005 and 0.024 ± 0.007, cholesterol diet groups; 0.029 ± 0.007 and 0.034 ± 0.005 for non-injured and injured arteries). In metabolite analysis, most of the radioactivity was found in the aqueous fraction in each group (87.4-94.6% of total radioactivity in the arteries), and glutamate was a dominant component (67.4-69.7% of the aqueous fraction in the arteries). Conclusions: The level of [14C]acetate-derived radioactivity into the arteries was increased by balloon injury and the burden of a cholesterol diet. Water-soluble metabolites were the dominant components with radioactivity in the atherosclerotic lesions. These results provide a biological basis for imaging atherosclerotic lesions by PET using [11C]acetate

In vitro uptake and metabolism of [14C]acetate in rabbit atherosclerotic arteries: biological basis for atherosclerosis imaging with [11C]acetate

AbstractIntroductionDetection of vulnerable plaques is critically important for the selection of appropriate treatment and/or the prevention of atherosclerosis and ensuing cardiovascular diseases. In order to clarify the utility of [11C]acetate for atherosclerosis imaging, we determined the uptake and metabolism of acetate by in vitro studies using rabbit atherosclerotic arteries and [14C]acetate.MethodsRabbits were fed with a conventional (n = 5) or a 0.5% cholesterol diet (n = 6). One side of the iliac–femoral arteries was injured by a balloon catheter. Radioactivity levels in the iliac–femoral arteries were measured after incubation in DMEM containing [1-14C]acetate for 60 min (% dpm/mg tissue). Radioactive components in the homogenized arteries were partitioned into aqueous, organic, and residue fractions by the Folch method, and analyzed by thin-layer chromatography (TLC).ResultsThe radioactivity level in the injured arteries of rabbits fed with the 0.5% cholesterol diet (atherosclerotic arteries) was significantly higher than that in either the non-injured or injured arteries of rabbits fed with the conventional diet (p < 0.05) (% dpm/mg tissue: conventional diet groups; 0.022 ± 0.005 and 0.024 ± 0.007, cholesterol diet groups; 0.029 ± 0.007 and 0.034 ± 0.005 for non-injured and injured arteries). In metabolite analysis, most of the radioactivity was found in the aqueous fraction in each group (87.4–94.6% of total radioactivity in the arteries), and glutamate was a dominant component (67.4–69.7% of the aqueous fraction in the arteries).ConclusionsThe level of [14C]acetate-derived radioactivity into the arteries was increased by balloon injury and the burden of a cholesterol diet. Water-soluble metabolites were the dominant components with radioactivity in the atherosclerotic lesions. These results provide a biological basis for imaging atherosclerotic lesions by PET using [11C]acetate

Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a heterothermic mammal

The naked mole-rat (NMR) is a heterothermic mammal that forms eusocial colonies consisting of one reproductive female (queen), several reproductive males, and subordinates. Despite their heterothermy, NMRs possess brown adipose tissue (BAT), which generally induces thermogenesis in cold and some non-cold environments. Previous studies suggest that NMR-BAT induces thermogenesis by cold exposure. However, detailed NMR-BAT characteristics and whether NMR-BAT thermogenesis occurs in non-cold environments are unknown. Here, we show beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential of NMR-BAT, which contributes to thermogenesis in the isolated queen in non-cold environments (30 degrees C). NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment (20 degrees C), it was insufficient to prevent the decrease in the body temperatures. Even at 30 degrees C, NMRs are known to prevent the decrease of and maintain their body temperature by heat-sharing behaviors within the colony. However, isolated NMRs maintained their body temperature at the same level as when they are in the colony. Interestingly, we found that queens, but not subordinates, induce BAT thermogenesis in this condition. Our research provides novel insights into NMR thermoregulation