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The tenant of this hypothesis is that loss of tolerance would not occur if the zonulin-dependent intestinal barrier function is restored, thereby preventing the influence of environmental triggers in individuals genetically susceptible to autoimmunity. This review outlines the current research and a structured hypothesis on how a dysregulated small intestinal epithelial barrier, a "leaky gut", may be important in the pathogenesis of autoimmunity in certain individuals at risk of both T1D and celiac disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.There is minimal evidence of EGFR-mutated lung adenocarcinoma transforming to small cell lung carcinoma (SCLC) without the administration of EGFR-tyrosine kinase inhibitor (TKI). Here, we present a case of EGFR/PTEN co-mutated lung adenocarcinoma with lymph node metastases, which comprised adenocarcinoma admixed with SCLC. EGFR L858R and PTEN R130Q mutations were shared between the primary tumor and lymph node metastasis. Additionally, EGFR I744M mutation was shared between the adenocarcinoma and SCLC components in the lymph node metastasis, confirming spontaneous transformation from adenocarcinoma to SCLC. Furthermore, TP53 and RB1 mutations were detected only in the SCLC components of the lymph node metastasis. Immunohistochemically, complete absence of Rb expression in SCLC was observed, suggesting the loss of function of RB1. Our case clearly shows that EGFR/PTEN co-mutated lung adenocarcinoma transformed to SCLC in the lymph node without TKI-mediated evolutionary selection pressures. © 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.In the 1980s when surgery was first introduced for the treatment of atrial fibrillation (AF), one would often hear comments like "Every little old grandmother has AF. Why on earth would you operate on someone like that?". © 2020 Wiley Periodicals, Inc.We review Don Gilbert's pioneering seminal contributions that both detailed the mathematical principles and the experimental demonstration of several of the key dynamic characteristics of life. Long before it became evident to the wider biochemical community, Gilbert proposed that cellular growth and replication necessitate autodynamic occurrence of cycles of oscillations that initiate, coordinate, and terminate the processes of growth, during which all components are duplicated and become spatially re-organized in the progeny. Initiation and suppression of replication exhibit switch-like characteristics i.e., bifurcations in the values of parameters that separate static and autodynamic behavior. His limit cycle solutions present models developed in a series of papers reported between 1974 and 1984, and these showed that most or even all of the major facets of the cell division cycle could be accommodated. That the cell division cycle may be timed by a multiple of shorter period (ultradian) rhythms, gave further credence to the central importance of oscillatory phenomena and homeodynamics as evident on multiple time scales (seconds to hours). Further application of the concepts inherent in limit cycle operation as hypothesized by Gilbert more than 50 years ago are now validated as being applicable to oscillatory transcript, metabolite and enzyme levels, cellular differentiation, senescence, cancerous states, and cell death. Now, we reiterate especially for students and young colleagues, that these early achievements were even more exceptional, as his own lifetime's work on modeling was continued with experimental work in parallel with his predictions of the major current enterprises of biological research. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that is part of the family of tyrosine kinase receptors. selleck kinase inhibitor The binding of EGFR to its cognate ligands leads to its autophosphorylation and subsequent activation of the signal transduction pathways involved in regulating cellular proliferation, differentiation, and survival. Accordingly, this receptor carries out both redundant and restricted functions in the germline development of mammals and in the maintenance of various adult tissues. Correspondingly, the loss of EGFR regulation results in many human diseases, with the most notable cancer. This receptor is overexpressed and/or mutated in multiple epithelial-derived tumors, and associated with poor prognosis and survival in cancer patients. Here, we discuss in detail the role of EGFR in specific epithelial-derived cancer pathologies; these include lung cancer, colorectal cancer, and squamous cell carcinomas. The development of multiple anticancer agents against EGFR diminished the progression and metastasis of tumors. Some of the most versatile therapeutic anti-EGFR agents include the monoclonal antibodies (mAbs), demonstrating success in clinical settings when used in combination with cytotoxic treatments, such as chemotherapy and/or radiation. We thus discuss the development and application of two of the most notable therapeutic mAbs, cetuximab, and panitumumab, currently utilized in various EGFR-related epithelial cancers. © 2020 International Federation for Cell Biology.INTRODUCTION The Medtronic Attain Stability Quad lead is a quadripolar left ventricular (LV) lead with an active fixation helix assembly designed to fixate the lead within the coronary sinus and pace nonapical regions of the LV. The primary objective of this study was to determine the safety and effectiveness of this novel active fixation quadripolar LV lead. METHODS Patients with standard indications for cardiac resynchronization therapy (CRT) were enrolled. All patients were followed at 3 and 6 months post-implant and every 6 months thereafter until study closure. Pacing capture thresholds (PCTs) were measured at implant and each follow-up and adverse events (AEs) were recorded upon occurrence. RESULTS Of the 440 patients who underwent implant procedures, placement of the Attain Stability Quad lead was successful in 426 (96.8%). LV lead-related complications occurred in 10 patients (2.3%), including LV lead dislodgement in three patients (0.7%). The percentage of patients with at least one LV pacing vector with a PCT ≤2.