Amphibian thrombocyte-derived extracellular vesicles,including microRNAs,induce angiogenesis-related genes in endothelial cells

Thrombocytes circulate in the blood of nonmammalian vertebrates and are involved in hemostasis; however, many detailed characteristics of thrombocytes remain unclear. Recently, we established an amphibian thrombocyte cell line. Here, we report the finding that thrombocytes produce integrin alpha IIb (CD41)-positive extracellular vesicles (EVs), which include microRNAs (miRs). Flow cytometric analysis showed the expression of CD41⁺ and phosphatidylserine on the surface of EVs. Nanotracking analysis showed that these CD41⁺ EVs were approximately 100 nm in diameter. As CD41⁺ EVs were also observed from African clawed frogs, the production of CD41⁺ EVs might be common to amphibians. Microarray analysis showed that the CD41⁺ EVs contain many kinds of miRs. These CD41⁺ EVs were phagocytosed by endothelial cells and macrophages. qPCR analysis showed that many angiogenesis-related genes were up-regulated in CD41⁺ EV-treated endothelial cells. Over-expression of some miRs in the CD41⁺ EVs increased the proliferation of endothelial cells. These results indicated that thrombocytes produced CD41⁺ EVs, including miRs, that were received by endothelial cells to induce the expression of angiogenesis-related genes. These results indicated that the CD41⁺ EVs produced from thrombocytes act as signaling molecules to repair damaged blood vessels.     

Multifocal and microscopic chromophobe renal cell carcinomatous lesions associated with ‘capsulomas’ without FCLN gene abnormality

Chromophobe renal cell carcinoma (RCC) accounts for approximately 5% of renal epithelial neoplasms. Multiple and/or bilateral chromophobe RCCs in an individual are generally rare but frequently occur in patients with Birt–Hogg–Dubé syndrome (BHDS) and in patients with tuberous sclerosis complex (TSC). The responsible genes in both BHDS and TSC act as tumor suppressors. Therefore, it seems that some genetic backgrounds are required for the generation and progression of multiple chromophobe RCCs. Here, we report a case of multiple and bilateral chromophobe RCCs along with several small‐sized capsular angiomyolipomas known as ‘capsulomas’ in a 39‐year‐old woman who had neither a particular medical history nor specific gene mutation. There has been no report of sporadic multiple chromophobe RCCs and ‘capsulomas’ developing in a patient without genetic features, having potential for novel genetic variation.     

Reliability of the Cutting Alignment Scoring Tool (CAST) to Assess Trunk and Limb Alignment During a 45-Degree Side-Step Cut

BackgroundThree-dimensional (3D) motion analysis is considered the gold standard for evaluating human movement. However, its clinical utility is limited due to cost, operating expertise, and lengthy data processing time. Numerous qualitative scoring systems have been introduced to assess trunk and lower extremity biomechanics during functional tasks. However, the reliability of qualitative scoring systems to evaluate cutting movements is understudied. Purpose/Hypotheses: To assess the inter-rater and intra-rater reliability of the Cutting Alignment Scoring Tool (CAST) among sports medicine providers and to evaluate rater agreement of each component of the CAST. The hypotheses were: 1) there would be good–to-excellent inter-rater and intra-rater reliability among sports medicine providers, 2) there would be good to almost perfect agreement for cut width and trunk lean variables and moderate to good agreement for valgus variables of the CAST.Study DesignRepeated MeasuresMethodsTen videos of a 45-degree side-step cut performed by adolescent athletes were independently rated on two occasions by six raters (2 medical doctors, 2 physical therapists, and 2 athletic trainers). The variables assessed include trunk lean to the opposite direction of the cut, increased cut width, knee valgus at initial load acceptance (static), and knee valgus throughout the task (dynamic). Variables were scored as either present, which were given a score of “1”, or not present, which were given a score of “0”. Video sequence was randomized in each rating session, and a two-week wash out period was given.ResultsThe cumulative inter-rater and intra-rater reliabilities were good (ICC: 0.808 and ICC: 0.753). Almost perfect kappa coefficients were recorded for cut width (k=0.949). Moderate kappa coefficients were found for trunk lean (k= 0.632) and fair kappa coefficients were noted for dynamic and static valgus (k=0.462 and k= 0.533 respectively).ConclusionThese findings suggest that the CAST is a reliable tool to evaluate trunk and LE alignment during a cutting task by sports medicine providers.Level of EvidenceLevel 2 Diagnosis     

Visualization of the Peripheral Branches of the Mandibular Division of the Trigeminal Nerve on 3D Double-Echo Steady-State with Water Excitation Sequence

BACKGROUND AND PURPOSE:Although visualization of the extracranial branches of the cranial nerves has improved with advances in MR imaging, only limited studies have assessed the detection of extracranial branches of the mandibular nerve (V3). We investigated the detectability of the branches of V3 on a 3D double-echo steady-state with water excitation sequence.MATERIALS AND METHODS:We retrospectively evaluated the detectability of the 6 branches of the V3, the masseteric, buccal, auriculotemporal, lingual, inferior alveolar, and mylohyoid nerves, by using a 5-point scale (4, excellent; 3, good; 2, fair; 1, poor; and 0, none) in 86 consecutive patients who underwent MR imaging with the 3D double-echo steady-state with water excitation sequence. Weighted κ analysis was used to calculate interobserver variability among the 3 readers.RESULTS:The detection of the lingual and inferior alveolar nerves was the most successful, with excellent average scores of 3.80 and 3.99, respectively. The detection of the masseteric, the buccal, and the auriculotemporal nerves was good, with average scores of 3.31, 2.67, and 3.11, respectively. The mylohyoid nerve was difficult to detect with poor average scores of 0.62. All nerves had excellent interobserver variability across the 3 readers (average weighted κ value, 0.95–1.00).CONCLUSIONS:The 3D double-echo steady-state with water excitation sequence demonstrated excellent visualization of the extracranial branches of V3 in most patients. The 3D double-echo steady-state with water excitation sequence has the potential for diagnosing V3 pathologies and preoperatively identifying peripheral cranial nerves to prevent surgical complications.

Cranial nerve deficits are not uncommon, and there are many pathologic processes that can affect the cranial nerves.^1–10 Unfortunately, the physical examination findings are often nonspecific for differentiating among these pathologic causes, and imaging plays a crucial role in diagnosing pathologic processes affecting the cranial nerves. With increasing spatial and contrast resolution of cross-sectional imaging, better visualization of the cranial nerves and their major branches has become possible, but the delineation of the entire course of the extracranial segments of the cranial nerves still remains a diagnostic challenge.^11–17The trigeminal nerve has the largest distribution of innervation among all the cranial nerves in the suprahyoid neck. Even though the mandibular nerve (V3) is the largest division of the trigeminal nerve, there have been only limited studies investigating the visualization of the extracranial segments of V3 with MR imaging. Several prior studies have focused on imaging the extracranial segments of V3 by using a T1-weighted fast-spoiled gradient recalled-echo sequence with fat suppression,⁹ a T1-weighted MPRAGE sequence with water excitation fat suppression,¹⁸ or a diffusion tensor tractography sequence,¹⁹ but these studies evaluated only the inferior alveolar nerve. Another study used FIESTA and fast-spoiled gradient recalled-echo sequences to evaluate the entire V3 nerve, but the extracranial peripheral V3 branches were not well-demonstrated, with the exception of the inferior alveolar and lingual nerves.¹³The 3D double-echo steady-state with water excitation (3D-DESS-WE) sequence is a recently introduced MR imaging technique that can delineate the peripheral cranial nerves as high-signal-intensity structures.²⁰ At our institution, this sequence has been added to our standard MR imaging protocol of the salivary glands and has been used routinely to evaluate the intraparotid facial nerve and salivary ducts within the salivary glands since October 2012. The purpose of this study was to investigate the detectability of the extracranial peripheral branches of V3 on the 3D-DESS-WE sequence.