Conditional deletion of Bmpr1a in differentiated osteoclasts increases osteoblastic bone formation, increasing volume of remodeling bone in mice

Bone undergoes remodeling consisting of osteoclastic bone resorption followed by osteoblastic bone formation throughout life. Although the effects of bone morphogenetic protein (BMP) signals on osteoblasts have been studied extensively, the function of BMP signals in osteoclasts has not been fully elucidated. To delineate the function of BMP signals in osteoclasts during bone remodeling, we deleted BMP receptor type IA ( Bmpr1a ) in an osteoclast‐specific manner using a knock‐in Cre mouse line to the cathepsin K locus ( Ctsk Cre/+ ;Bmpr1a flox/flox , designated as Bmpr1a ΔOc/ΔOc ). Cre was specifically expressed in multinucleated osteoclasts in vivo. Cre‐dependent deletion of the Bmpr1a gene occurred at 4 days after cultivation of bone marrow macrophages obtained from Bmpr1a ΔOc/ΔOc with RANKL. These results suggested that Bmpr1a was deleted after formation of osteoclasts in Bmpr1a ΔOc/ΔOc mice. Expression of bone‐resorption markers increased, thus suggesting that BMPRIA signaling negatively regulates osteoclast differentiation. Trabeculae in tibia and femurs were thickened in 3.5‐, 8‐, and 12‐week‐old Bmpr1a ΔOc/ΔOc mice. Bone histomorphometry revealed increased bone volume associated with increased osteoblastic bone‐formation rates (BFR) in the remodeling bone of the secondary spongiosa in Bmpr1a ΔOc/ΔOc tibias at 8 weeks of age. For comparison, we also induced an osteoblast‐specific deletion of Bmpr1a using Col1a1‐Cre. The resulting mice showed increased bone volume with marked decreases in BFR in tibias at 8 weeks of age. These results indicate that deletion of Bmpr1a in differentiated osteoclasts increases osteoblastic bone formation, thus suggesting that BMPR1A signaling in osteoclasts regulates coupling to osteoblasts by reducing bone‐formation activity during bone remodeling. © 2011 American Society for Bone and Mineral ResearchPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87086/1/477_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87086/2/jbmr_477_sm_SupplData.pd

Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population

departmental bulletin pape

キョウブ ダイドウミャク ジンコウ ケッカン チカン ジュツゴ ニ カッケツ トケツ オ キタシタ サイシュジュツ ショウレイ ノ セイセキ

【緒言】胸部大動脈疾患に対する人工血管置換術後に、喀血・吐血を来して再手術を要した症例の背景、予後を報告する。【症例】当院で2012年1月から2020年12月までに、喀血・吐血を主訴に胸部大動脈手術を行った24例中、人工血管置換術後の19例（喀血11、吐血8）を対象とした。【結果】年齢中央値73歳（49 - 88歳）、男性12例、女性7例、17例は緊急で手術を行った。初回手術からの間隔は中央値435日（55 - 1883日）であり、初回手術は上行置換1例、下行置換7例、弓部置換11例であった。手術適応は人工血管感染11例、仮性動脈瘤7例、急性大動脈解離1例であった。感染症例の内、9例に大動脈食道瘻を認めた。今回手術は、下行置換6例、胸腹部置換1例、弓部置換3例、ステントグラフト8例、自己弁温存基部置換術１例であった。全体の在院死亡は6例（32%）、生存者の術後滞在期間の中央値は101日であった。大動脈食道瘻を来した症例のうち6例は、2期的に食道抜去も施行し、その在院死亡は33%であった。一方、食道抜去を施行しなかった3例の在院死亡は67%であった。感染の有無で2群に分け検討したところ、在院死亡に統計学的有意差は認めなかった（p=0.147）。Kaplan-Meier法による全体の3年生存率は22.8%と不良であり、感染を認めた群では2年生存率9%と極めて不良であった。【結論】胸部人工血管置換後に喀血・吐血を来した症例の中でも、人工血管感染を生じた症例の予後は極めて不良であった。特に大動脈食道瘻を認めた場合は、食道抜去が必要であると考えられる。Introduction:We report the conditions and outcomes of patients suffering thoracic aortic disease, who developed hematemesis and hemoptysis and required reoperation.Patients: From January 2012 to December 2020, 19 patients (11 hemoptysis, 8 hematemesis) who had previous thoracic aortic surgery required reoperation with the main complaint of hemoptysis and hematemesis. Results:The median age was 71.5 years; there were 7 females, and 17 urgent cases. The median interval since the previous surgery was 435 days (55 to 1883 days), and the previous surgeries were 1 ascending aorta replacement, 7 descending aorta replacements, and 11 total arch replacements. The indications for reoperation were infection in 11 cases, pseudoaneurysm in 7 cases, and acute aortic dissection in 1 case. Aortoesophageal fistula was found in 9 of the infected cases. The surgical actions were 6 descending aorta replacements, 1 thoracoabdominal aorta replacement, 3 total arch replacements, 8 stent grafts, and 1 valve-sparing root reconstruction. Only one patient, who suffered aortic rupture due to dissection, died within 30 days. Six of the cases with aortoesophageal fistula also underwent esophagectomy in the second phase. There were 6 in-hospital mortality cases (32%), and the median length of stay after surgery for survivors was 101 days. The patients were divided into two groups according to the presence of infection, but the difference in-hospital mortality (infection (-): 13%, (+): 45%, p = 0.147) was not statistically significant. The 3-year survival rate by the Kaplan-Meier method was 23% overall, but the 2-year survival rates were 9% in the infected group and 53% in the non-infected group (Log-rank p= 0.167). Conclusion:Among the patients developing hemoptysis and hematemesis after previous thoracic aortic surgery, the cases of graft infection had extremely poor prognosis. Especially when aortoesophageal fistula is found, it is necessary to consider esophagectomy immediately

サイセンタン ノ サンジゲン イメージング システム : シンゾウ ケッカン ゲカ ニオケル Virtual Reality ギジュツ ノ ユウヨウセイ

滋賀医科大学心臓血管外科では医療用画像を三次元構築し、臓器を立体表示するVirtual Reality (VR) 技術を用いて心臓血管系の3D解析研究を進めている。VRでは臓器の内腔を可視化することができ、また3D構築した画像に直接介入し、従来の2D解析では評価困難であった複雑な構造も術者の視点で直観的に計測できるという利点がある。あらゆる医療画像データを三次元化し, かつ直感的な立体計測が可能なVR技術は, これまでの診断精度を上回る形態学的な情報を臨床医に提示し得ると考えられる。特に外科医にとって有用な手術支援VR画像は, 難易度が高い手術の治療成績を向上させる可能性が高い。Adequate preoperative planning may facilitate successful procedures in cardiovascular surgery. We have newly developed a system the Vesalius 3D suite, combining three-dimensional (3D) image-processing software with an optic-tracking spatial navigation, allowing quick, accessible 3D image interpretation for virtual reality (VR) exploration and measurement of complex anatomy. In this review, we present a novel method of virtual imaging analysis for preoperative planning and simulation in cardiovascular operation using this 3D-VR system. Based on unimodal or multimodal medical imaging data, DICOM data sets can be reconstructed for 3D visualization. Virtually reconstructed images can be viewed on stereoscopic 3D display, revealing each patient’s specific anatomy and the internal structures in exquisite detail. Highly accessible 3D interpretation promptly permits precise and intuitive measurements of repair-relevant anatomical parameters including geometrically complex shapes. This technology may promote understanding of form and function in the cardiovascular system, and facilitate operative procedures in more challenging cases. Furthermore, this system can be especially valuable for any surgeon to gain experience in practicing for rarely-performed procedures or uncommon patient-specific preoperative surgical simulations

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

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe