The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory reaction in the premetastatic niche

The capture of tumour-derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably to the formation of the pre-metastatic niche (PMN). However, due to the challenges associated with modelling release of small EVs in vivo, the kinetics of PMN formation in response to endogenously released TEVs have not been examined. Here, we have studied the endogenous release of TEVs in mice orthotopically implanted with metastatic human melanoma (MEL) and neuroblastoma (NB) cells releasing GFP-tagged EVs (GFTEVs) and their capture by host cells to demonstrate the active contribution of TEVs to metastasis. Human GFTEVs captured by mouse macrophages in vitro resulted in transfer of GFP vesicles and the human exosomal miR-1246. Mice orthotopically implanted with MEL or NB cells showed the presence of TEVs in the blood between 5 and 28 days after implantation. Moreover, kinetic analysis of TEV capture by resident cells relative to the arrival and outgrowth of TEV-producing tumour cells in metastatic organs demonstrated that the capture of TEVs by lung and liver cells precedes the homing of metastatic tumour cells, consistent with the critical roles of TEVs in PMN formation. Importantly, TEV capture at future sites of metastasis was associated with the transfer of miR-1246 to lung macrophages, liver macrophages, and stellate cells. This is the first demonstration that the capture of endogenously released TEVs is organotropic as demonstrated by the presence of TEV-capturing cells only in metastatic organs and their absence in non-metastatic organs. The capture of TEVs in the PMN induced dynamic changes in inflammatory gene expression which evolved to a pro-tumorigenic reaction as the niche progressed to the metastatic state. Thus, our work describes a novel approach to TEV tracking in vivo that provides additional insights into their role in the earliest stages of metastatic progression.The authors would like to thank Mrs. J. Rosenberg for her help in the formatting of the manuscript, and the personnel of the Core Facilities of the Saban Research Institute at Children's Hospital Los Angeles (Flow Cytometry, Extracellular Vesicle, Cell Imaging, and Animal Imaging Cores) for their expertise and assistance. This work was supported by National Institutes of Health/National Cancer Institute grant R01 CA207983 to Y.A. DeClerck

Examination of Selective Low-pressure Fine Needle Aspiration Cytology Under Ultrasound Guidance

Cytology by fine-needle cytology is indispensable for diagnosing head and neck tumor, especially for thyroid nodule. There are two methods of fine needle cytology; one of fine-needle aspiration cytology (FNAC and another of fine-needle non-aspiration cytology (FNNAC). These previous procedures has each disadvantage such as the mixing of blood or low yield of cells. We proposed a new technique: selective low-pressure fine needle aspiration cytology (SLOP-FNAC) to overcome the backwards of previous procedures. We used the scoring system by Mair et al. to evaluate smear quality of specimens obtained with FNNAC and SLOP-FNAC. SLOP-FNAC smears exhibited higher scores in amount of cellular material, degree of cellular degeneration and cell yield, and retention of appropriate architecture compared to FNNAC smears. The SLOP-FNAC smears scored significantly higher for amount of cellular material and retention of appropriate architecture evaluated (P = 0.0261 and P = 0.0024, Student’s t-test). SLOP-FNAC may be a useful cell sampling technique that reduces blood contamination while securing a high cell yield with maintaining tissue structure

Epidemiology of Coronavirus Disease Outbreak among Crewmembers on Cruise Ship, Nagasaki City, Japan, April 2020

In April 2020, a coronavirus disease (COVID-19) outbreak occurred on the cruise ship Costa Atlantica in Nagasaki, Japan. Our outbreak investigation included 623 multinational crewmembers onboard on April 20. Median age was 31 years; 84% were men. Each crewmember was isolated or quarantined in a single room inside the ship, and monitoring of health status was supported by a remote health monitoring system. Crewmembers with more severe illness were hospitalized. The investigation found that the outbreak started in late March and peaked in late April, resulting in 149 laboratory-confirmed and 107 probable cases of infection with severe acute respiratory syndrome coronavirus 2. Six case-patients were hospitalized for COVID-19 pneumonia, including 1 in severe condition and 2 who required oxygen administration, but no deaths occurred. Although the virus can spread rapidly on a cruise ship, we describe how prompt isolation and quarantine combined with a sensitive syndromic surveillance system can control a COVID-19 outbreak

Seismic imaging of a carbonate rock block with fracture-induced anisotropy

International audienceSeismic experiments on a meter-scale rock sample characterize spatial heterogeneities at outcrop scale, and potentially bridge the gap between laboratory experiments and conventional field seismic experiments. Using a real seismic dataset of a fractured carbonate rock sample, we demonstrate strong potentials of small rock-block experiments, and endeavor towards full waveform analyses, such as full waveform inversion. We were able to place sources and receivers to surround the sample and acquired the data to optimally illuminate internal structures along chosen 2D planes. The observed waveforms comprised clear but complicated P- and S-wave direct arrivals and free surface reflections from all sides of the block. Beam forming (slant-stacking) was capable of extracting hidden complex arrivals. By exploiting both P and S arrivals, we successfully estimated parameters of apparent tilted transverse anisotropy with a symmetry axis normal to the 10 cm-scale fractures. In order to delineate heterogeneities in the sample due to fractures, we proposed to apply full waveform inversion to the dataset. With synthetic studies, we illustrated that the velocity model can be nearly perfectly reconstructed at a half-wavelength scale

Status of periodontal diseases in Junior high school students

歯周疾患は齲蝕とならぶ口腔の二大疾患である。歯周疾患は中高年に罹患者が多いとされているが, 若年性歯周炎のように10代から発症する場合もある。今回, 10代前半である中学生を対象に歯周状態について縦断調査を行う機会を得た。対象は2009年度に本学附属中学校に在籍した中学2年生で, 中学1年生時に歯周疾患に関する口腔内診査を行った生徒68名とした。口腔内診査では, Gingival index(GI), Probing depth(PD)およびBleeding index(BI)を測定した。その結果, PDはこれまでの報告と類似しており, GIおよびBIはともにこれまでの報告と比較し, 低い値であった。これは, 歯肉炎有病者率は高いが, 軽度の歯肉炎の者が多かったと考えられる。しかし, GI, PDは1年生時から2年生時に増加を認めており, 今後も悪化する可能性が考えられるため, 注意深く経過を追う必要がある。さらに, PDが4㎜あった生徒もいるので, 個別の対応を検討していく必要があると考える