A new tool for investigation platelet activation in endometriosis patients

Objectives: Endometriosis (EM) is a gynecological disease characterized by chronic inflammation, due to the interaction of inflammatory cells with ectopic endometrium (1). Platelets (PLTs), recruited by procoagulant factors released from endometriotic stromal cells, secrete angiogenetic factors and induce overexpression of genes involved in pro-survival/ anti-apoptotic propensity, inflammationand extracellular matrix remodeling (2). We aimed to develop a tool to measure PLT activation (by small extracellular vesicles, s-EVs) in EM peritoneal fluids, as a potential predictive marker of EM severity. Materials & methods: S-EVs were isolated from EM peritoneal fluids and characterized with imaging (Atomic Force Microscopy; AFM) and protein expression analyses (Western blot, WB) (3). We explored gene expression in peritoneum and EM lesions using EndometDB (4). Results: We demonstrated the presence of s-EVs isolated from EM peritoneal fluids by liquid AFM, as showed by contact angle vs diameter scatterplot (Fig.1A-B), and by WB detecting the s-EV markers CD63, CD9, and TSG101 (Fig.1C). Using Endomet-DB, we highlighted the differentially expressed genes between control and EM peritoneum samples (Fig.1D). The protein expression of a panel of biomarkers of PTL in s-EVs was further confirmed by WB (Fig.1E). Conclusions: We propose applying s-EV research to EM investigation, generating a novel biochemical tool for PLT activation assessment and for the development of new diagnostics and therapies

Mast Cells in Peritoneal Fluid From Women With Endometriosis and Their Possible Role in Modulating Sperm Function

Endometriosis is a local pelvic inflammatory process, frequently associated with infertility, with altered function of immune-related cells in the peritoneal environment. Mast cells are known to be key players of the immune system and have been recently involved in endometriosis and in infertility, with their mediators directly suppressing sperm motility. In this study, we evaluated the mast cell population and their mediators in the peritoneal fluid of infertile patients with endometriosis and their impact on human sperm motility. Peritoneal fluids, collected by laparoscopy from 11 infertile patients with endometriosis and 9 fertile controls were evaluated for the presence of mast cells, tryptase levels and their effect on sperm motility. Furthermore, an in vitro model of mast cells-sperm interaction in peritoneal fluid was set up, using LAD2 cell line as a mast cell model, and analyzed from a functional as well as a morphological point of view. Mast cell peritoneal fluid population and its main mediator, tryptase, is more represented in endometriosis confirming an involvement of these cells in this disease. Anyway it appears unlikely that tryptase enriched peritoneal fluid, which fails to inhibit sperm motility, could contribute to endometriosis associated infertility. Despite of this, sperm interaction with the mast cell surface (LAD2) induced a significantly mast cell-degranulation response in the peritoneal fluid from endometriosis which could directly modulate sperm function other than motility. This evidence lead us to suppose that there is, between these elements, an interrelationship which deserves further studies

Is the complement protein C1q a pro- or anti-tumorigenic factor? Bioinformatics analysis involving human carcinomas

C1q is the first subcomponent of the classical pathway of the complement system and belongs to the C1q/Tumor Necrosis Factor superfamily. C1q can perform a diverse range of immune and non-immune functions in a complement-dependent as well as -independent manner. Being a pattern recognition molecule of the innate immunity, C1q can recognize a number of self, non-self and altered-self ligands and bring about effector mechanisms designed to clear pathogens via opsonisation and inflammatory response. C1q is locally synthesized by macrophages and dendritic cells, and thus, can get involved in a range of biological processes, such as angiogenesis and tissue remodeling, immune modulation, and immunologic tolerance. The notion of C1q involvement in the pathogenesis of cancer is still evolving. C1q appears to have a dual role in cancer: tumor promoting as well as tumor-protective, depending on the context of the disease. In the current study, we performed a bioinformatics analysis to investigate whether C1q can serve as a potential prognostic marker for human carcinoma. We used the Oncomine database and the survival analysis platforms Kaplan-Meier plotter. Our results showed that high levels of C1q have a favorable prognostic index in basal-like breast cancer for disease-free survival, and in HER2-positive breast cancer for overall survival, while it showed a pro-tumorigenic role of C1q in lung adenocarcinoma, and in clear cell renal cell carcinoma. This in silico study, if validated via a retrospective study, can be a step forward in establishing C1q as a new tool as a prognostic biomarker for various carcinoma.Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Ital

Pathological significance and prognostic value of Surfactant Protein D in cancer

Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance via phagocytosis and super-oxidative burst. It can interfere with allergen-IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line via p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression via interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma via Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan-Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts, are probably less susceptible to SP-D-mediated immune surveillance mechanisms via infiltrating immune cells

Detention and mapping of iron and toxic environmental elements in human ovarian endometriosis: A suggested combined role

Background: Endometriosis is a disease affecting 10-15 % of women worldwide, consisting in the ectopic growth of endometrial cells outside the uterine cavity. Whist the pathogenetic mechanisms of endometriosis remain elusive and contemplating even environmental causes, iron deposits are common in endometrial lesions, indicating an altered iron metabolism at this level. This study was undertaken to reveal a possible relationship between iron dysmetabolism and accumulation of environmental metals. Methods: By combining histological and histochemical analysis (H&E and Perl's staining) with μ- and nano- synchrotron-based (SR-based) X-ray Fluorescence (XRF) microscopy, we investigated the distribution of iron and other elements in the ovarian endometriomas of 12 endometriosis patients and in 7 healthy endometrium samples. Results: XRF microscopy expanded the findings obtained by Perl's staining, revealing with an exceptional sensitivity intracellular features of iron accumulation in the epithelial endometrium, stroma and macrophages of the endometriotic lesions. XRF evidenced that iron was specifically accumulated in multiple micro aggregates, reaching concentrations up to 10-20 % p/p. Moreover, by XRF analysis we revealed for the first time the retention of a number of exogenous and potentially toxic metals such as Pb, Br, Ti, Al Cr, Si and Rb partially or totally co-localizing with iron. Conclusion: μXRF reveals accumulation and colocalization of iron and environmental metals in human ovarian endometriosis, suggesting a role in the pathogenesis of endometriosis

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration.

The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-mm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) in vitro. Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested in vitro, dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE

Position statement of the Brazilian Academy of Rhinology on the use of antihistamines, antileukotrienes, and oral corticosteroids in the treatment of inflammatory sinonasal diseases

Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors' needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugshowever, final considerations about the role of each of them have been made. (C) 2017 Published by Elsevier Editora Ltda. on behalf of Associacao Brasileira de Otorrino-laringologia e Cirurgia Cervico-Facial.Univ Sao Paulo, Disciplina Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Otorrinolaringol, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Ciencias Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Otorrinolaringol, Sao Paulo, SP, BrazilUniv Fed Minas Gerais, Fac Med, Belo Horizonte, MG, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP, BrazilUniv Fed Bahia, Fac Med, Disciplina Otorrinolaringol, Salvador, BA, BrazilHosp Inst Paranaense Otorrinolaringol, Centro Rinite & Alergia, Curitiba, PR, BrazilUniv Estado Rio De Janeiro, Rio De Janeiro, RJ, BrazilUniv Brasilia, Fac Med, Brasilia, DF, BrazilUniv Fed Sao Paulo, Dept Otorrinolaringol & Cabeca & Pescoco, Sao Paulo, SP, BrazilUniv Luterana Brasil, Fac Med, Otorrinolaringol, Canoas, RS, BrazilMt Sinai Hosp, Dept Othorhinolaryngol, Toronto, ON, CanadaUniv Sao Paulo, Fac Med, Ciencias, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Ciencias Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Otorrinolaringol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Otorrinolaringol & Cabeca & Pescoco, Sao Paulo, SP, BrazilWeb of Scienc

How to avoid the inappropriate use of antibiotics in upper respiratory tract infections? A position statement from an expert panel

Introduction: Bacterial resistance burden has increased in the past years, mainly due to inappropriate antibiotic use. Recently it has become an urgent public health concern due to its impact on the prolongation of hospitalization, an increase of total cost of treatment and mortality associated with infectious disease. Almost half of the antimicrobial prescriptions in outpatient care visits are prescribed for acute upper respiratory infections, especially rhinosinusitis, otitis media, and pharyngotonsillitis. In this context, otorhinolaryngologists play an important role in orienting patients and non-specialists in the utilization of antibiotics rationally and properly in these infections. Objectives: To review the most recent recommendations and guidelines for the use of antibiotics in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, adapted to our national reality. Methods: A literature review on PubMed database including the medical management in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, followed by a discussion with a panel of specialists. Results: Antibiotics must be judiciously prescribed in uncomplicated acute upper respiratory tract infections. The severity of clinical presentation and the potential risks for evolution to suppurative and non-suppurative complications must be taken into 'consideration'. Conclusions: Periodic revisions on guidelines and recommendations for treatment of the main acute infections are necessary to orient rationale and appropriate use of antibiotics. Continuous medical education and changes in physicians' and patients' behavior are required to modify the paradigm that all upper respiratory infection needs antibiotic therapy, minimizing the consequences of its inadequate and inappropriate use. (C) 2018 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license.Introdução: A resistência bacteriana a antibióticos nos processos infecciosos é um fato crescente nos últimos anos, especialmente devido ao seu uso inapropriado. Ao longo dos anos vem se tornando um grave problema de saúde pública devido ao prolongamento do tempo de internação, elevação dos custos de tratamento e aumento da mortalidade relacionada às doenças infecciosas. Quase a metade das prescrições de antibióticos em unidades de pronto atendimento é destinada ao tratamento de alguma infecção de vias aéreas superiores, especialmente rinossinusites, otite média aguda supurada e faringotonsilites agudas, sendo que uma significativa parcela dessas prescrições é inapropriada. Nesse contexto, os otorrinolaringologistas têm um papel fundamental na orientação de pacientes e colegas não especialistas, para o uso adequado e racional de antibióticos frente a essas situações clínicas. Objetivos: Realizar uma revisão das atuais recomendações de utilização de antibióticos nas otites médias, rinossinusites e faringotonsilites agudas adaptadas à realidade nacional. Método: Revisão na base PubMed das principais recomendações internacionais de tratamentos das infecções de vias aéreas superiores, seguido de discussão com um painel de especialistas. Resultados: Os antibióticos devem ser utilizados de maneira criteriosa nas infecções agudas de vias aéreas superiores não complicadas, a depender da gravidade da apresentação clínica e dos potenciais riscos associados de complicações supurativas e não supurativas. Conclusões: Constantes revisões a respeito do tratamento das principais infecções agudas são necessárias para que sejam tomadas medidas coletivas no uso racional e apropriado de antibióticos. Somente com orientação e transformações no comportamento de médicos e pacientes é que haverá mudanças do paradigma de que toda infecção de vias aéreas superiores deva ser tratada com antibióticos, minimizando por consequência os efeitos de seu uso inadequado.Univ Fed Rio Grande do Sul, Dept Oftalmol & Otorrinolaringol, Fac Med FAMED, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, EPM, Sao Paulo, SP, BrazilUniv Estadual Campinas, UNICAMP, Dept Otorrinolaringol & Oftalmol, Campinas, SP, BrazilUniv Sao Paulo, FM, Disciplina Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, FM, Otorrinolaringol, Sao Paulo, SP, BrazilHosp Infantil Sabara, Otorrinolaringol, Sao Paulo, SP, BrazilHosp Paranaense Otorrinolaringol IPO, Inst Paranaense Otorrinolaringol, Curitiba, Parana, BrazilFac Ciencias Med Santa Casa de Sao Paulo, Sao Paulo, SP, BrazilUniv Fed Pernambuco UFPE, Dept Cirurgia, Div Otorrinolaringol, Recife, PE, BrazilUniv Luterana Brasil, Fac Med, Porto Alegre, RS, BrazilUniv Sao Paulo, FM, Sao Paulo, SP, BrazilHosp Albert Einstein, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv Fed Ciencias Saude Porto Alegre, Hosp Crianca St Antonio, Serv Otorrinolaringol Pediat, Porto Alegre, RS, BrazilUniv Estado Rio De Janeiro, Fac Ciencias Med, Disciplina Otorrinolaringol, Rio De Janeiro, RJ, BrazilUniv Fed Goias, Goiania, Go, BrazilPontificia Univ Catolica Goias PUC GO, Goiania, Go, BrazilCtr Univ Anapolis, Anapolis, Go, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, EPM, Sao Paulo, SP, BrazilSciEL

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level