Large asymptomatic Left Atrial Myxoma with ossification: case report

<p>Abstract</p> <p>Background</p> <p>Atrial myxomas are the most common primary cardiac tumors. They are usually small or moderate in size by the time of the diagnosis, exhibiting non specific cardiac or systemic symptoms, and are most frequently soft and friable without microscopic signs of ossification. We describe herein an extremely rare case of an asymptomatic giant left atrial myxoma with angiographic neovascularization and ossification.</p> <p>Case presentation</p> <p>An asymptomatic 58-year-old male with a giant left atrial tumor, was transferred to our Unit for surgical treatment. The tumor was an incidental finding during a work-up for hemoptysis due to bronchectasis. The coronary angiogram showed tumor vessels originating from the RCA. The tumor macroscopically did not resemble a myxoma, considering its dimensions (12 × 10 cm) and its solid substance. The mass was excised together with the interatrial septum and the right lateral LA wall close to the right pulmonary veins orifices. The defect was closed with Dacron patches in order to prevent malformation of both atria. The pathology study revealed a benign myxoma with excessive osteoid (mature bone) content.</p> <p>Conclusion</p> <p>We consider our case as extremely rare because of the asymptomatic course despite the large size of the tumor, the blood supply from the right coronary artery and the bone formation.</p

Exploration of T cell immune responses by expression of a dominant-negative SHP1 and SHP2

SHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs and ITSMs on inhibitory immune receptors. Consequently, SHP1 and SHP2 are key proteins in the transmission of inhibitory signals within T cells, constituting an important point of convergence for diverse inhibitory receptors. Therefore, SHP1 and SHP2 inhibition may represent a strategy for preventing immunosuppression of T cells mediated by cancers hence improving immunotherapies directed against these malignancies. Both SHP1 and SHP2 contain dual SH2 domains responsible for localization to the endodomain of inhibitory receptors and a protein tyrosine phosphatase domain which dephosphorylates and thus inhibits key mediators of T cell activation. We explored the interaction of the isolated SH2 domains of SHP1 and SHP2 to inhibitory motifs from PD1 and identified strong binding of both SH2 domains from SHP2 and more moderate binding in the case of SHP1. We next explored whether a truncated form of SHP1/2 comprising only of SH2 domains (dSHP1/2) could act in a dominant negative fashion by preventing docking of the wild type proteins. When co-expressed with CARs we found that dSHP2 but not dSHP1 could alleviate immunosuppression mediated by PD1. We next explored the capacity of dSHP2 to bind with other inhibitory receptors and observed several potential interactions. In vivo we observed that the expression of PDL1 on tumor cells impaired the ability of CAR T cells to mediate tumor rejection and this effect was partially reversed by the co-expression of dSHP2 albeit at the cost of reduced CAR T cell proliferation. Modulation of SHP1 and SHP2 activity in engineered T cells through the expression of these truncated variants may enhance T cell activity and hence efficacy in the context of cancer immunotherapy

System size and centrality dependence of the balance function in A+A collisions at sqrt[sNN]=17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

System size and centrality dependence of the balance function in A + A collisions at sqrt s NN = 17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si and centrality selected Pb+Pb collisions at sqrt s_NN = 17.2$ GeV with the NA49 large acceptance detector at the CERN-SPS. In particular, long range pseudo-rapidity correlations of oppositely charged particles were measured using the Balance Function method. The width of the Balance Function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

Exploration of T cell immune responses by expression of a dominant-negative SHP1 and SHP2

SHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs and ITSMs on inhibitory immune receptors. Consequently, SHP1 and SHP2 are key proteins in the transmission of inhibitory signals within T cells, constituting an important point of convergence for diverse inhibitory receptors. Therefore, SHP1 and SHP2 inhibition may represent a strategy for preventing immunosuppression of T cells mediated by cancers hence improving immunotherapies directed against these malignancies. Both SHP1 and SHP2 contain dual SH2 domains responsible for localization to the endodomain of inhibitory receptors and a protein tyrosine phosphatase domain which dephosphorylates and thus inhibits key mediators of T cell activation. We explored the interaction of the isolated SH2 domains of SHP1 and SHP2 to inhibitory motifs from PD1 and identified strong binding of both SH2 domains from SHP2 and more moderate binding in the case of SHP1. We next explored whether a truncated form of SHP1/2 comprising only of SH2 domains (dSHP1/2) could act in a dominant negative fashion by preventing docking of the wild type proteins. When co-expressed with CARs we found that dSHP2 but not dSHP1 could alleviate immunosuppression mediated by PD1. We next explored the capacity of dSHP2 to bind with other inhibitory receptors and observed several potential interactions. In vivo we observed that the expression of PDL1 on tumor cells impaired the ability of CAR T cells to mediate tumor rejection and this effect was partially reversed by the co-expression of dSHP2 albeit at the cost of reduced CAR T cell proliferation. Modulation of SHP1 and SHP2 activity in engineered T cells through the expression of these truncated variants may enhance T cell activity and hence efficacy in the context of cancer immunotherapy

Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease resulting in global muscular weakness and, frequently, in respiratory failure and premature death. Gene-based therapies like Nusinersen are now available for patients with SMA. The aim of this review was to assess in &ldquo;real world&rdquo; studies, whether novel treatments would have a positive impact on the mechanical ventilatory support requirements of SMA patients, already initiated on ventilatory support prior to treatment administration. A literature search was performed in Pubmed using multiple combinations of MESH terms and the snowball procedure. A total of 14 publications were discussed in this review. Considering all patients included in the published studies who were on ventilatory support and were treated with Nusinersen, 13/172 (7.5%) had reduced needs for ventilatory support, 1/172 (0.6%) did not need ventilation post-treatment, and 122/172 (70.9%) were maintained on the same ventilator settings. Moreover, 2/41 (4.9%) children who were offered gene therapy had no need for further ventilatory support and 12/41 (29.2%) had reduced requirements. In conclusion, available evidence suggests that among children with SMA, who are on mechanical respiratory support either noninvasively or via tracheostomy at the time of gene-based treatment, only a few will be weaned off the ventilator or have reduced ventilator needs per 24 h. Children will usually require the same level of support as before treatment

Ρητορική του μίσους στο διαδίκτυο: Εννοιολογικό πλαίσιο και πολιτικές αντιμετώπισης

Εισαγωγή Η ρητορική του μίσους στο διαδίκτυο είναι ένα φαινόμενο συνεχώς εντεινόμενο στις σύγχρονες φυσικές και διαδικτυακές κοινωνίες. Σκοπός της παρούσας εργασίας είναι η παρουσίαση της συχνότητας του φαινομένου, των αιτιών και συνεπειών του, των χαρακτηριστικών των θυμάτων, ώστε να κατανοήσουμε καλύτερα το εννοιολογικό πλαίσιο. Επίσης σκοπός είναι η παρουσίαση των διαφόρων υποβάθρων οργάνωσης προγραμμάτων και εκστρατειών για την καταπολέμηση του φαινομένου. Υλικά και Μέθοδος Πραγματοποιήθηκε εκτενής ανασκόπηση της βιβλιογραφίας. Η αναζήτηση έγινε σε ποικίλες βάσεις δεδομένων, καθώς και στα σχετικά έγγραφα οργανισμών της Ευρωπαϊκής Ένωσης και των Ηνωμένων Εθνών. Κατά την αναζήτηση βιβλιογραφίας χρησιμοποιήθηκε επιπλέον η τεχνική της «χιονοστιβάδας». Για τις ανάγκες της αναζήτησης βιβλιογραφίας χρησιμοποιήθηκαν κατάλληλες λέξεις κλειδιά ώστε να αναδυθούν όλα τα επι μέρους θέματα που πραγματεύτηκε η παρούσα εργασία (ορισμοί, συχνότητα, αίτια, συνέπειες, προγράμματα καταπολέμησης, κα) Αποτελέσματα Έγινε αντιληπτή η ποικιλία ορισμών του φαινομένου στη βιβλιογραφία, τα νομικά και επιστημονικά κείμενα καθώς και η συχνότητά του μέσα από τα αποτελέσματα ευρωπαϊκών μελετών. Παρουσιάστηκε το επιστημονικό υπόβαθρο των εκστρατειών που διοργανώνονται για την καταπολέμηση του φαινομένου, δηλαδή του ψηφιακού αλφαβητισμού, της αγωγής του πολίτη και εμπέδωσης των ανθρωπίνων δικαιωμάτων όπως και των μεθόδων κοινωνικοσυναισθηματικής μάθησης. Συμπεράσματα Από τη μελέτη μας φάνηκε η πολυπλοκότητα και οι βαθιές ρίζες του φαινομένου στις κοινωνίες, φυσικές και κατ’ επέκταση διαδικτυακές καθώς και η ευαλωτότητα των νέων ως προς αυτό και η συχνότητα με την οποία έρχονται αντιμέτωποί του. Τα προγράμματα καταπολέμησης της ρητορικής του μίσους στο διαδίκτυο θα πρέπει να είναι ολιστικά στοχεύοντας στον ψηφιακό αλφαβητισμό, αγωγή του πολίτη και ενδυνάμωση των νέων μέσα από τεχνικές κοινωνικοσυναισθηματικής μάθησης. Θα πρέπει τέλος να στοχεύουν στη μακροπρόθεσμη διατήρηση των καλών τους αποτελεσμάτων.Introduction Hate speech online is a growing problem in the modern physical and virtual societies, which mostly affects young people. In this study we aimed to provide a better understanding of the definition, the frequency, the causes and consequences of the phenomenon as well as to identify some special features of the victims. Another aim of this study is the presentation of the background-philosophy of the campaigns and projects aiming to counter this phenomenon. Methods and Materials A comprehensive search on different databases, such as PubMed and Google Scholar, was implemented, as well as in legal and policy documents of the European Union and the United Nations. We used some appropriate ―key words‖ in order all the aspects of the phenomenon (definitions, frequency, causes, consequences, counternarrative campaigns etc) to emerge. We used the ―snowball procedure‖ to complete our desktop research. Results A variety of definitions of the phenomenon in the literature, the legal and scientific documents, as well as its frequency were shown through the results of European studies. The scientific background of some projects, aiming to tackle the phenomenon, was presented to wit the digital literacy, the citizenship and human rights education, as well as the social and emotional learning methods. Conclusions Our study revealed the complexity of the phenomenon and its deep roots in the human societies, connecting the phenomenon in the physical and virtual world. The vulnerability of the youth and the frequency were also discussed. The countering campaigns should be including holistically the digital literacy, the citizenship education of citizens and the empowerment of the youth using social and emotional learning methods, in view of the longterm preservation of their good results

Myocarditis in a Pediatric Patient with <i>Campylobacter</i> Enteritis: A Case Report and Literature Review

Myocarditis represents a potential complication of various infectious and noninfectious agents and a common diagnostic challenge for clinicians. Data regarding Campylobacter-associated myocarditis are limited. Here, a case of a 13-year-old female with Campylobacter jejuni gastroenteritis complicated by myocarditis is presented, followed by a literature review in order to retrieve information about Campylobacter-associated carditis in the pediatric population. A search on MEDLINE/PubMed yielded 7relevant cases in the last 20 years. Most of them (six/seven) were males and the mean age was 16.1 years. All patients presented with gastrointestinal symptoms followed in six/seven cases by chest pain within two to seven days. Campylobacter was isolated from stool cultures in six patients; abnormal electrocardiographic findings were detected in six; and abnormal echocardiographic findings in three of the cases. Five patients were treated with antibiotics. Full recovery was the clinical outcome in six patients, whereas one patient died. Concerning the nonspecific symptoms of patients with myocarditis, high clinical suspicion of this complication is necessary in cases where patients with a recent infection present with chest pain and elevated cardiac biomarkers

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring in vitro Drug Delivery from MOFs in Real Time

Metal-organic frameworks (MOFs) have been proposed as biocompatible candidates for the targeted intracellular delivery of chemotherapeutic payloads, but the site of drug loading and subsequent effect on intracellular release is often overlooked. Here, we analyze doxorubicin delivery to cancer cells by MIL-101(Cr) and UiO-66 in real time. Having experimentally and computationally verified that doxorubicin is pore loaded in MIL-101(Cr) and surface loaded on UiO-66, different time-dependent cytotoxicity profiles are observed by real-time cell analysis and confocal microscopy. The attenuated release of aggregated doxorubicin from the surface of Dox@UiO-66 results in a 12 to 16 h induction of cytotoxicity, while rapid release of pore-dispersed doxorubicin from Dox@MIL-101(Cr) leads to significantly higher intranuclear localization and rapid cell death. In verifying real-time cell analysis as a versatile tool to assess biocompatibility and drug delivery, we show that the localization of drugs in (or on) MOF nanoparticles controls delivery profiles and is key to understanding in vitro modes of action