224 research outputs found

    Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus).

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    We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms. [Abstract copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

    Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

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    The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Psychotherapy and Psychosomatics

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    E' una rivista in lingua inglese recensita in CC e PubMed. L'impact factor del 2007 \ue8 5.0

    Conflicts of interest.

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    The issue of conflict of interest has brought clinical medicine to an unprecedented crisis of credibility. Corporate actions that have placed profit over public health have become regular news in the media. The public seems to be increasingly sceptical of the integrity of medical practice, including psychiatry. Clinicians are more and more disoriented because of the discrepancy between the campaigns to shape a favourable climate of opinion for new drugs and the disappointing results in practice. Attempts to control conflict of interests by simple disclosure have yielded very limited results. A radical proposal for addressing the issue of conflict of interest in psychiatry and regaining credibility is advanced. It is based on the definition of \u201csubstantial\u201d conflict of interest: being an employee of a private company; being a regular consultant or in the board of directors of a company; being a stockholder of a company related to the field of research; owning a patent directly related to the published work. Occasional consultancies, grants for performing investigations, or receiving honoraria or refunds in specific occasions would not be a source of substantial conflict of interest. Psychiatric investigators who hold positions in scientific societies, medical journals (editorship), groups for guidelines and clinical matters, should be devoid of substantial conflict of interest. Disclosure is no longer sufficient for the independence of the psychiatric field

    Psychotherapy and Psychosomatics

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    E' una rivista in lingua inglese recensita in CC and PubMed. L'impact factor del 2004 \ue8 3.99 che la colloca tra le 5 pi\uf9 importanti riviste di psicologi
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