Extracellular nanovesicles secreted by human osteosarcoma cells promote angiogenesis

Angiogenesis involves a number of different players among which extracellular nanovesicles (EVs) have recently been proposed as an efficient cargo of pro-angiogenic mediators. Angiogenesis plays a key role in osteosarcoma (OS) development and progression. Acidity is a hallmark of malignancy in a variety of cancers, including sarcomas, as a result of an increased energetic metabolism. The aim of this study was to investigate the role of EVs derived from osteosarcoma cells on angiogenesis and whether extracellular acidity, generated by tumor metabolism, could influence EVs activity. For this purpose, we purified and characterized EVs from OS cells maintained at either acidic or neutral pH. The ability of EVs to induce angiogenesis was assessed in vitro by endothelial cell tube formation and in vivo using chicken chorioallantoic membrane. Our findings demonstrated that EVs derived from osteosarcoma cells maintained either in acidic or neutral conditions induced angiogenesis. The results showed that miRNA and protein content of EVs cargo are correlated with pro-angiogenic activity and this activity is increased by the acidity of tumor microenvironment. This study provides evidence that EVs released by human osteosarcoma cells act as carriers of active angiogenic stimuli that are able to promote endothelial cell functions relevant to angiogenesis

A proposal of classification for machine-learning vibration-based damage identification methods

Recent advances in computing power and sensing technology led to a significant evolution of Structural Health Monitoring (SHM) techniques, transforming SHM into a “Big Data” problem. The use of data-driven approaches for damage identification purposes, specifically Machine Learning (ML) methods, has gained popularity. ML can help at various levels of the SHM process: to pre-and post-process input data, extract damage sensitive features, and operate pattern recognition in measured data and output valuable information for damage identification. In this paper, the role of ML in SHM applications is discussed together with a new scheme for classifying ML applications in SHM, especially focusing on vibration-based monitoring, given its consolidated theoretical base. Finally, the implications of the application of these methods to historic structures are discussed, with a brief account of existing case studies. The proposed classification is exemplified using the most recent studies available in the literature on cultural heritage structures.- (undefined

Response to Dr Greenwood’s Comments on “Extending the Double-Hertz Model to Allow Modeling of an Adhesive Elliptical Contact”

© 2018, The Author(s). An adhesive elliptical contact is normally found in microscale applications that involve cylindrical solids, crossing at an angle between 0° and 90°. Currently, only one model is available to describe the elliptical contact’s surface interaction: the approximate Johnson–Kendall–Roberts (JKR) model which is limited to soft materials. In this paper, a new adhesive elliptical model is developed for a wide range of adhesive contacts by extending the double-Hertz theory, where adhesion is modeled by the difference between two Hertzian pressure distributions. Both Hertzian pressures are assumed to have an equivalent shape of contact areas, the only difference being in size. Assuming that the annular adhesive region is obtained by the area difference between the two Hertzian contact areas, the pull-off force curves can be calculated. In the limiting case of an adhesive circular contact, the results are very close to results from the existing models. However, for an adhesive elliptical contact in the JKR domain, lower pull-off forces are predicted when compared to the JKR values. Unlike the developed model, the shape of the JKR contact area varies throughout contact. Results show, particularly for conditions close to the JKR domain, that it is important to take into account that the adhesive region is the result of the two Hertzian contact areas having a non-equivalent shape

Why Me? To Be an Ultra-Responder to Antiplatelet Therapy: A Case Report

Background: Platelet function testing is a valid tool to investigate the clinical response to antiplatelet therapy in different clinical settings; in particular, it might supply helpful information in patients with cerebrovascular disease. Oral antiplatelet treatment, such as Aspirin (ASA) and Clopidogrel, is the gold standard in secondary stroke prevention of non-cardiogenic ischemic stroke; conversely, its application as a primary prevention therapy is not routinely recommended in patients with vascular risk factors. Multiple electrode platelet aggregometry (MEA) impedance aggregometer is a validated device to test platelet inhibition induced by ASA or Clopidogrel. Case Report: We report the case of a 78-year-old patient without relevant clinical history, taking ASA as primary prevention strategy, who was admitted for sudden onset of dysarthria and left facial hyposthenia during physical effort. Brain CT revealed two small subcortical bilateral spontaneous intracranial hemorrhages. Platelet aggregometry with MEA performed upon admission revealed a very strong platelet inhibition induced by ASA (result of the ASPI Test was 5 U, consistent with an ultra-responsiveness to ASA, and the cutoff value of correct responsiveness is <40 U). MRI at longitudinal follow-up revealed the presence of two small cavernous angioma underlying hemorrhagic spots. Conclusion: The evaluation of platelet reactivity in stroke patients undergoing antiplatelet therapies, not commonly performed in clinical practice, could be useful to optimize prevention strategies; the verification of the biological effectiveness of ASA or Clopidogrel could be a valid tool in the definition of each patient's risk profile, particularly in patients with cerebrovascular disease known to be at increased risk for both hemorrhagic and thrombotic complications

Exosomes: Novel effectors of human platelet lysate activity

Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies

The masks of Lorenzo Tenchini : their anatomy and surgical/bioengineering clues

An academic, anatomist, and Lombrosian psychiatrist active at the University of Parma in Italy at the end of the 19th century, Lorenzo Tenchini produced ceroplastic-like masks that are unique in the anatomical Western context. These were prepared from 1885 to 1893 with the aim of 'cataloguing' the behaviour of prison inmates and psychiatric patients based on their facial surface anatomy. Due to the lack of any reference to the procedure used to prepare the masks, studies were undertaken by our group using X-ray scans, infrared spectroscopy, bioptic sampling, and microscopy analysis of the mask constituents. Results showed that the masks were stratified structures including plaster, cotton gauze/human epidermis, and wax, leading to a fabrication procedure reminiscent of 'additive layer manufacturing'. Differences in the depths of these layers were observed in relation to the facial contours, suggesting an attempt to reproduce, at least partially, the three-dimensional features of the facial soft tissues. We conclude the Tenchini masks are the first historical antecedent of the experimental method for face reconstruction used in the early 2000s to test the feasibility of transferring a complete strip of face and scalp from a deceased donor to a living recipient, in preparation for a complete face transplant. In addition, the layering procedure adopted conceptually mimics that developed only in the late 20th century for computer-aided rapid prototyping, and recently applied to bioengineering with biomaterials for a number of human structures including parts of the skull and face. Finally, the masks are a relevant example of mixed ceroplastic-cutaneous preparations in the history of anatomical research for clinical purposes

Treatment with class a CpG oligodeoxynucleotides in cats with naturally occurring feline parvovirus infection: A prospective study

Feline parvovirus (FPV) causes severe gastroenteritis and leukopenia in cats; the outcome is poor. Information regarding specific treatments is lacking. Class A CpG oligodeoxynucleotides (CpG-A) are short single-stranded DNAs, stimulating type I interferon production. In cats, CpG-A induced an antiviral response in vivo and inhibited FPV replication in vitro. The aim was to prospectively investigate the effects of CpG-A on survival, clinical score, hematological findings, antiviral response (cytokines), viremia, and fecal shedding (real-time qPCR) in cats naturally infected with FPV. Forty-two FPV-infected cats were randomized to receive 100 g/kg of CpG-A (n = 22) or placebo (n = 20) subcutaneously, on admission and after 48 h. Blood and fecal samples were collected on admission, after 1, 3, and 7 days. All 22 cats showed short duration pain during CpG-A injections. The survival rate, clinical score, leukocyte and erythrocyte counts, viremia, and fecal shedding at any time-point did not differ between cats treated with CpG-A (50%) and placebo (40%). Antiviral myxovirus resistance (Mx) gene transcription increased in both groups from day 1 to 3 (p = 0.005). Antibodies against FPV on admission were associated with survival in cats (p = 0.002). In conclusion, CpG-A treatment did not improve the outcome in cats with FPV infection. FPV infection produced an antiviral response

Recurrent Ascending Colon Cancer Manifesting as Inferior Vena cava Thrombus

We report an extremely rare case of recurrent ascending colon cancer manifesting as inferior vena cava (IVC) thrombus. A 77-year-old woman previously diagnosed with ascending colon cancer underwent right hemicolectomy with lymph node dissection. Though the tumor invaded the retroperitoneum and involved the right ovarian artery and vein, curative operation was performed. The patient took 5-FU p.o. Two and a half years later, tumor thrombus in the IVC extending into the right atrium was incidentally found and diagnosed as recurrence of colon cancer by biopsy. RF-induced hyperthermia using 5-FU and CDDP i.v. was immediately performed, but she died after 6 months because of multiple liver and pulmonary metastases. In treating colon cancers invading the retroperitoneum, it should be recalled that some cases recur as tumor thrombus in the IVC and that close follow-up is therefore necessary