The lymphangiogenic growth factors VEGF-C and VEGF-D : Part 1: Basic principles and embryonic development

This journal is listed by Scopus and EMBASE/Excerpta Medica, but not by Web of Science...VEGF-C and VEGF-D are the two central signaling molecules that stimulate the development and growth of the lymphatic system. Both belong to the vascular endothelial growth factor (VEGF) protein family, which plays important roles in the growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis). In mammals, the VEGF family comprises five members: VEGF-A, PlGF, VEGF-B, VEGF-C and VEGF-D. The family was named after VEGF-A, the first member to be discovered. VEGF-C and VEGF-D form a subgroup within this family in terms of function and structure. Their distinctive biosynthesis differentiates them from the other VEGFs: they are produced as inactive precursors and need to be activated by proteolytic removal of their long N- and C-terminal propeptides. Unlike the other VEGFs, VEGF-C and VEGF-D are direct stimulators of lymphatic vessel growth. They exert their lymphangiogenic function via VEGF receptor 3, which is expressed in the adult organism almost exclusively on lymphatic endothelial cells. In this review, we provide an overview of the VEGF protein family and their receptors. We focus on the lymphangiogenic VEGF-C and VEGF-D, discussing their biosynthesis and their role in embryonic lymphangiogenesis.Peer reviewe

Rarely selected distractors in high stakes medical multiple-choice examinations and their recognition by item authors: A simulation and survey

Background Many medical exams use 5 options for multiple choice questions (MCQs), although the literature suggests that 3 options are optimal. Previous studies on this topic have often been based on non-medical examinations, so we sought to analyse rarely selected, 'non-functional' distractors (NF-D) in high stakes medical examinations, and their detection by item authors as well as psychometric changes resulting from a reduction in the number of options. Methods Based on Swiss Federal MCQ examinations from 2005-2007, the frequency of NF-D (selected by <1% or <5% of the candidates) was calculated. Distractors that were chosen the least or second least were identified and candidates who chose them were allocated to the remaining options using two extreme assumptions about their hypothetical behaviour: In case rarely selected distractors were eliminated, candidates could randomly choose another option - or purposively choose the correct answer, from which they had originally been distracted. In a second step, 37 experts were asked to mark the least plausible options. The consequences of a reduction from 4 to 3 or 2 distractors - based on item statistics or on the experts' ratings - with respect to difficulty, discrimination and reliability were modelled. Results About 70% of the 5-option-items had at least 1 NF-D selected by <1% of the candidates (97% for NF-Ds selected by <5%). Only a reduction to 2 distractors and assuming that candidates would switch to the correct answer in the absence of a 'non-functional' distractor led to relevant differences in reliability and difficulty (and to a lesser degree discrimination). The experts' ratings resulted in slightly greater changes compared to the statistical approach. Conclusions Based on item statistics and/or an expert panel's recommendation, the choice of a varying number of 3-4 (or partly 2) plausible distractors could be performed without marked deteriorations in psychometric characteristics

Passivrauchen in der Schweizer Bevölkerung 2009

Die Berichte zu diesem Thema geben Auskunft über die Passivrauchexposition der Schweizer Wohnbevölkerung und deren subjektiv empfundene Belästigung an verschiedenen Orten (Arbeitsort, Gaststätten, Veranstaltungsorte usw.). Des Weiteren wurden Fragen zur Akzeptanz von Massnahmen zum Schutz der Nichtrauchenden in öffentlichen Räumen erhoben. Ebenfalls wurde das Wissen bezüglich der Schädlichkeit des Passivrauchens erfrag

Exposure to and annoyance with second-hand smoke in Switzerland: results of the Tobacco Monitoring Survey

Summary.: Objectives: To present selected results on exposure to secondhand smoke and experienced annoyance with second-hand smoke in the Swiss population, particularly in restaurants and in the workplace. Methods: The data were collected as part of the Swiss Survey of Tobacco Use ("Tobacco Monitoring”) commissioned by the Swiss Federal Office of Public Health. It is a representative, continuous survey of tobacco consumption among 14- to 65-year-olds in Switzerland. Since January 2001, four times a year a new sample of 2 500 persons has been taken (i. e. 10 000 participants annually). The survey was conducted using standardized telephone interviews in German, French and Italian. Results: Approximately half of the working population in Switzerland is exposed to second-hand smoke in the workplace. In restaurants, cafes and bars, nearly 9 out of 10 people are exposed to environmental tobacco smoke. Non-smokers in particular report annoyance with second-hand smoke. Conclusions: The Swiss population has a high level of exposure to second-hand smoke. There is a need for public health educational programs and legislation aiming at banning smoking in public areas and in the workplac

Die Ausbildung in Methoden der empirischen Sozialforschung. Ergebnisse der Befragung der Lehrenden durch die AG "Methodenausbildung"

"Im Auftrag der Sektion Methoden der Deutschen Gesellschaft für Soziologie wurde im Wintersemester 2000/2001 eine Befragung der Lehrenden im Bereich 'Methoden der Empirischen Sozialforschung' an den Universitäten der BRD durchgeführt. Basierend auf den Antworten von 104 Befragten (das entspricht einer Rücklaufquote von 44%) werden Ergebnisse über Umfang und Dauer der Methoden- und Statistik-Ausbildung berichtet. Zusammenfassend muss die Ausbildung in ihrem Umfang an mehr als dreiviertel der Lehreinheiten als unzureichend angesehen werden. Entsprechend berichten ca. die Hälfte der Lehrenden von Problemen, sowohl der universitätsinternen als auch der universitätsextemen Nachfrage nach methodisch qualifizierten Absolventen zu entsprechen. Mehr als 80% der Nachfrage universitätsexterner Arbeitgeber richtet sich dabei auf rein quantitativ qualifizierte Absolventen. Zusammenfassend müssen diese Ergebnisse als eindeutige Belege für den Mangel an quantitativ ausgebildeten Sozialwissenschaftlern in der Bundesrepublik angesehen werden. Als Maßnahmen zur Behebung dieses Mangels wird vorgeschlagen, die Stundenzahl für die Methoden- und Statistikausbildung aller sozialwissenschaftlichen Studiengänge auszudehnen, sozialwissenschaftliche Studiengänge für potentielle Studierende klar als wissenschaftliche Studiengänge mit integralen formalen Bestandteilen zu kennzeichnen und an einigen Universitäten Aufbaustudiengänge 'Empirische Sozialforschung' einzurichten." (Autorenreferat

The lymphangiogenic growth factors VEGF-C and VEGF-D Part 2: The role of lymphangiogenic growth factors VEGF-C and VEGF-D in lymphatic disorders

Vascular endothelial growth factor C (VEGF-C) and VEGF-D are the two central signaling molecules that govern the development and growth of the lymphovascular system. The presence or absence of lymphangiogenesis plays a central and sometimes causative role in a variety of diseases. Therefore, molecules that govern lymphangiogenesis, especially VEGF-C and VEGFR-3, offer the possibility for therapeutic interventions. Although the blockade of lymphangiogenesis does not yet exist as an independent therapeutic concept, a number of anti-lymphangiogenic drugs are now being tested in clinical trials. The rationale is that targeting VEGF-C and VEGF-D can improve the current anti-angiogenic treatment, since tumors may deploy the angiogenic forms of VEGF-C and VEGF-D when VEGF-A-mediated angiogenesis is blocked therapeutically. Despite numerous attempts, no breakthroughs have occurred in pro-angiogenic thera- pies to date. Furthermore, pro-lymphangiogenic, VEGF-C- or VEGF-D-based, therapies have not yet even entered the clinical trial phase. However, one clinical study with VEGF- C is now in preparation, namely in combination with lymph node transplantation for the treatment of postmastectomy edema. Here, we review the roles that VEGF-C, VEGF-D and their receptors play in diseases involving the lymphatic vascular system, and we present possibilities for utilizing these molecules to stimulate lymphatic vessel growth to treat lymphedema, or to block their functions in order to inhibit tumor angiogenesis and tumor lymphangiogenesis.Peer reviewe

Inhibition of Vascular Endothelial Growth Factor Receptors 1 and 2 Attenuates Natural Killer Cell and Innate Immune Responses in an Experimental Model for Obliterative Bronchiolitis

Funding Information: Supported by the Helsinki University Hospital , the Sigrid Juselius Foundation , the Academy of Finland , Finska Läkaresällskapet , the Research and Science Foundation of Farmos , The Paulo Foundation , Jalmari and Rauha Ahokas Foundation , Aarne Koskelo Foundation , Päivi and Sakari Sohlberg Foundation , Finnish Pulmonary Association , Biomedicum Helsinki Foundation , Jane and Aatos Erkko Foundation , and the University of Helsinki . Funding Information: Supported by the Helsinki University Hospital, the Sigrid Juselius Foundation, the Academy of Finland, Finska L?kares?llskapet, the Research and Science Foundation of Farmos, The Paulo Foundation, Jalmari and Rauha Ahokas Foundation, Aarne Koskelo Foundation, P?ivi and Sakari Sohlberg Foundation, Finnish Pulmonary Association, Biomedicum Helsinki Foundation, Jane and Aatos Erkko Foundation, and the University of Helsinki. Publisher Copyright: © 2022 American Society for Investigative PathologyObliterative bronchiolitis (OB) after lung transplantation is a nonreversible, life-threatening complication. Herein, the role of vascular endothelial growth factor receptor (Vegfr)-1 and -2 was investigated in the development of obliterative airway disease (OAD), an experimental model for OB. The nonimmunosuppressed recipients underwent transplantation with fully major histocompatibility complex mismatched heterotopic tracheal allografts and received Vegfr1 and -2-specific monoclonal antibodies either alone or in combination, or rat IgG as a control. The treatment with Vegfr1- or -2-blocking antibody significantly decreased intragraft mRNA expression of natural killer cell activation markers early after transplantation. This was followed by reduced infiltration of Cd11b thorn cells and Cd4 thorn T cells as well as down-regulated mRNA expression of proinflammatory chemokines and profibrotic growth factors. However, blocking of both Vegfr1 and -2 was necessary to reduce luminal occlusion. Furthermore, concomitant inhibition of the calcineurin activation pathway almost totally abolished the development of OAD. This study proposes that blocking of Vegf receptors blunted natural killer cell and innate immune responses early after transplantation and attenuated the development of OAD. The results of this study suggest that further studies on the role of Vegfr1 and -2 blocking in development of obliterative airway lesions might be rewarding. (Am J Pathol 2022, 192: 254-269; https://doi.org/10.1016/ j.ajpath.2021.10.018)Peer reviewe