O-arm Navigation-Guided Surgical Resection and Posterior Fixation for a Large Sacral Schwannoma

Sacral schwannoma is a rare tumor with relatively few symptoms; it thus tends to be large at diagnosis and is challenging to treat surgically. We present the case of a 12-year-old girl with a large sacral schwannoma that was successfully surgically resected using O-arm navigation in a two-stage operation. First, we performed tumor resection from the posterior aspect with assisted O-arm navigation. One week later, resection from the anterior aspect was conducted with posterior spinopelvic fixation and fibula graft. We performed partial resection of the tumor from the anterior and posterior aspects as much as possible. O-arm navigation contributed to precise and safe tumor resection and implant insertion

Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring

Bisphenol A diglycidyl ether (BADGE) is an epoxy resin used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In this study, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. Female pregnant mice were fed with a diet containing BADGE (0.15 or 1.5 mg/kg/day) during gestation and lactation periods. In an open field test, the time spent in the corner area significantly increases in male mice of high-dose BADGE group at 5 weeks old. The histological analysis using offspring brain at postnatal day 1 delivered from BADGE (1.5 mg/kg/day)-treated dams demonstrates that positive signals of Forkhead box P2- and COUP-TF interacting protein 2 are restricted in each cortical layer, but not in the control brain. In addition, the maternal BADGE exposure reduces nestin-positive fibers of the radial glia and T-box transcription factor 2-positive intermediate progenitors in the inner subventricular zone. Furthermore, a direct BADGE exposure promotes neurite outgrowth and neuronal connection in the primary cultured cortical neurons. These data suggest that maternal BADGE exposure can accelerate neuronal differentiation in fetuses and induce anxiety-like behavior in juvenile mice

Development of an X-ray real-time stereo imaging technique using synchrotron radiation

An X-ray stereo imaging system with synchrotron radiation was developed to perform real-time stereo imaging and stereo angiography

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

Association between limb alignment and patient-reported outcomes after total knee arthroplasty using an implant that reproduces anatomical geometry

Abstract Background A kinematically aligned (KA) total knee arthroplasty (TKA) is expected to improve patient satisfaction, but its effect remains controversial. We investigated differences in patient-reported outcomes (PROs) between KA and non-KA TKAs using an implant that reproduces anatomical geometry. Methods TKAs for varus deformity were performed in consecutive 129 patients (149 knees) via a measured resection technique with conventional instruments. The femorotibial angle (FTA), hip-knee-ankle angle (HKAA), and the angle between the joint line and the line perpendicular to the mechanical axis (AJLMA) were measured postoperatively (mean 13.6 months), and an AJLMA of ≥ 2° was defined as kinematic alignment. Patients were assigned to two or three alignment categories in each measurement method, and the Knee Society Scores (KSS) and Japanese Knee Injury and Osteoarthritis Outcome Scores (J-KOOS) was compared among the groups. Results For patients assessed by FTA, an ADL-related J-KOOS subscale (J-KOOS-A) showed a significant difference between valgus and varus outliers (p < 0.05). When assessed by HKAA, neither the KSS nor J-KOOS subscales were significantly different among groups. When assessed by AJLMA, J-KOOS-A was significantly different between groups, and a group for AJLMA of ≥ 2° had higher scores than a group for AJLMA of < 2° (95% CI 0.323–7.763; p < 0.05). Conclusions Patients with an AJLMA of ≥ 2° reported significantly higher patient’s satisfaction regarding ADL. This suggests the importance of restoration of the physiological joint line which can be achieved via KA TKAs

The impact of postoperative inclination of the joint line on clinical outcomes in total knee arthroplasty using a prosthesis with anatomical geometry

Abstract The goal of this study was to investigate the impact of postoperative inclination of the joint line on clinical results after total knee arthroplasty (TKA) using a prosthesis with anatomical geometry. This study included 145 primary cruciate-retaining type of knee prosthesis with anatomical geometry. Three years postoperatively, clinical outcomes including the patient-reported outcomes (PROs) were recorded. Limb alignment was evaluated by the hip-knee-ankle (HKA) axis and inclination of the joint line was assessed by the joint line orientation angle (JLOA). Knees were divided into two groups according to the HKA: in-range (− 3 to 3°) and outlier group ( 3°) or the JLOA: in-range (2–4°) and outlier group ( 4°), and clinical outcomes were compared between the groups. Postoperative Knee Society Function Score (KS-FS) was significantly higher in the HKA in-range group than the outlier group (p = 0.01). The Knee Society Knee Score and all subscales of the Knee injury Osteoarthritis Outcome Score were comparable between the groups. A multivariate analysis revealed a significant association between age at operation and postoperative KS-FS > of 80 points. Neither HKA in-range nor JLOA in-range were associated with the higher knee function. In conclusion, TKA-postoperative inclination of the joint line was not relevant to the short-term PROs. Treatment strategies that attempt to make joint line inclination in order to improve postoperative PROs should be avoided, and alignment goals such as kinematic alignment should be considered carefully