Prenatal Diagnosis of Interrupted Aortic Arch: Usefulness of Three-Vessel and Four-Chamber Views

Interrupted aortic arch (IAA) is fatal if not diagnosed. Prenatal diagnosis is helpful, but it is difficult to detect IAA and even more so to differentiate types A and B prenatally. Our objectives were to find a way to detect IAA using 2 views—three-vessel view (3VV) and four-chamber view (4CV)—and to differentiate between types A and B. We retrospectively analyzed fetal echocardiographic images and medical records of eight IAA patients. All eight patients had a ventricular septal defect (VSD) on 4CV. The aorta/main pulmonary artery (Ao/MPA) diameter ratio on 3VV was significantly low, which is characteristic of type B IAA. The left/right ventricular diameter (LV/RV) ratio on 4CV was 0.61± 0.17 for type A and almost 1.0 for type B. The thymus was not observed on 3VV in some type B IAA patients. These findings suggest that we could increase the number of prenatal diagnoses of IAA using the Ao/MPA ratio on 3VV and the presence of VSD on 4CV. Additionally, we could differentiate types A and B with the LV/RV ratio on 4CV, the Ao/MPA ratio, and the presence of a thymus on 3VV, which results in better management of IAA after birth

障害児通所施設における重症児の栄養アセスメントの現状

障害児通所施設における重症児の栄養アセスメントの現状を明らかにすることを目的に、全国の施設を対象に質問紙調査を行い320施設より回答を得、施設利用者の主障害が肢体不自由と知的障害で、年齢区分が幼児期と青年期である160施設の回答を分析した。その結果、青年期、幼児期ともに体重計測、喫食率の実施率は高く、体重変化率と体脂肪率の実施率は低かった。栄養評価(判定)の実施は、幼児期、青年期ともに2割と少なく、青年期はBMI、血清アルブミン、喫食率、幼児期はカウプ指数と成長曲線を評価(判定)の指標としている施設が多かったが、幼児期、青年期とも明確な基準値はなく、模索状態にあることが窺えた

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

The cleavage site specificity of human prostate specific antigen for insulin-like growth factor binding protein-3

AbstractThe cleavage site of human insulin-like growth factor binding protein-3 by urinary prostate specific antigen was examined. human insulin-like growth factor binding protein-3 was incubated with urinary prostate specific antigen at 37°C and its proteolyzed fragments were separated by a reversed phase HPLC followed by N-terminal amino acid sequence analysis, demonstrating that the cleavage mainly occurred at Tyr-159. The synthetic peptide including Tyr-159 was also cleaved at the same site, although its reaction rate was relatively low. These results indicate that human insulin-like growth factor binding protein-3 is specifically cleaved at Tyr-159 by prostate specific antigen. human insulin-like growth factor binding protein-3 was previously reported to be cleaved at five sites including Arg-97, Arg-132, Tyr-159, Phe-173 and Arg-179 by another group, however, prostate specific antigen preparation is possibly contaminated by trypsin-like protease. In contrast, our purified urinary prostate specific antigen had only a chymotrypsin-like activity, demonstrating that prostate specific antigen has the high substrate specificity for human insulin-like growth factor binding protein-3

Combined treatment with basalt stone and placenta extract to improve the chronic pain and scar after breast cancer surgery: a case report

Abstract Background The changes in body image caused by breast deformities and postoperative pain have a detrimental influence on the physical and mental health of patients with breast cancer. The postoperative quality of life (QOL) of these patients reduces significantly owing to the changes in the breast, an organ unique to women, that occur following breast cancer surgery. Case presentation This case report presents the case of a Asian woman in her early 40 s with postoperative hypertrophic scarring and contraction of the scar following mastectomy; the patient presented with decreased range of motion of the upper arm, hyperpigmentation from radiation burns, changes in breast shape, and chronic pain. The patient received a combination therapy comprising Basalt Stone Treatment and the application of horse placenta extract. As a result of a total of eight sessions conducted once every two weeks, the patient's pain and scar improved. No adverse events were observed after the therapy. Conclusion Combination therapy with Basalt Stone Treatment and horse placenta extract improved the chronic pain and scar after breast cancer surgery