Differenziell exprimierte Gene im Fettgewebe und ihre Rolle in der Pathophysiologie des humanen Metabolischen Syndroms

The human metabolic syndrome is characterized by a heterogenic complex of symptoms, including central obesity. Obesity itself is linked to major features of the metabolic syndrome such as insulin resistance, dyslipidemia or type 2 diabetes mellitus. It has been shown that obesity risk and resulting metabolic alterations are associated with adipose tissue distribution, adipocyte size and secretion of adipocytokines, which are in turn influenced by environmental factors and genetic susceptibility. It might be assumed that currently known genetic variants associated with obesity and/or BMI (body mass index) as well as fat distribution explain up to 20 % of the variability in BMI and so, studies employing novel strategies are inevitable. In addition to the role of genetic variation, mRNA levels of several genes have been shown to be differentially expressed in subcutaneous (SC) and visceral (Vis) adipose tissue and to be correlated with obesity-related traits. It is scarcely investigated whether the obesity risk variants also might account for the variability in mRNA expression. The present thesis deals with novel obesity candidate genes, characterized by a differential mRNA expression in various fat depots. The association of genetic variants in these genes with obesity as part of the metabolic syndrome, and related traits was investigated in well characterized German cohorts. The main method used for genotyping was described in detail in a comprehensive review providing explicit troubleshooting and description of modified protocols for specific experimental needs. Further, the influence of genotypes on the gene expression levels was examined. While the differential expression for FTO could be described for the first time, the variant rs8050136 was shown to be significantly associated with obesity but not with the expression. Genetic variants in FASN were shown to be significantly associated with obesity and related traits in a cohort of European ancestry for the very first time. Moreover, one polymorphism showed effects on the ratio of Vis/SC FASN mRNA expression. While CNR1 is controversially discussed in the literature, the present work showed rather moderate effects of genetic variants on obesity. BMPR2 could be described as a novel obesity candidate gene. Amongst others, one variant was associated with obesity in a case-control design and with BMPR2 mRNA expression in Vis adipose tissue. In conclusion, the present study revealed novel genetic variants promoting obesity, and therefore a metabolic risk, which might be partly explicable through an influence of these variants on the mRNA expression levels of the genes in the adipose tissue depots. These findings contribute to better understanding of the genetic background of obesity which is essential in order to translate experimental data into diagnostic, preventive and treatment strategies

Development of German pedelec (and bicycle) accidents between 2012 and 2020

In the recent years, pedelecs (pedal electric cycles) have seen a massive growth. in ridership. In 2013, around 1.3 million e-bilces were on German roads, while in 2020, this number was already at 8.5 million (with about 99% of the e-bikes being pedelecs). The rapid spread of pedelecs has given rise to concerns for road safety, especially due to the fact that riders of electric bicycles reach higher speeds. Indeed, some studies have reported that pedelec riders suffer from more severe crashes than users of conventional bikes. However, the highly dynamic development in pedelec ownership and use might cast some doubts on the long term validity of investigations of pedelec accidents and their characteristics that have to rely on data collected over shorter periods of time. Therefore, the aim of this study was to investigate pedelec accidents and their characterutics over several years in a longitudinal fashion. and compare them to accidents involving cyclists, tobe able to identify trends, and to clarify whether such trends are specifiic to pedelecs. [From: Introduction

Can Information About an Approaching Bicycle’s Characteristics Influence Drivers’ Gap Acceptance and TTA Estimates?

E-bikes, which have the potential to reach higher speed levels than conventional bicycles, but look basically the same, are suspected to be at a higher crash risk than such conventional bicycles. Other road users might misjudge the time remaining before the approaching bicycle arrives (time to arrival, TTA) and accept unsafe gaps (e.g. for turning manoeuvres) as a result of this combination of higher speed and well-known looks. Researchers have therefore suggested to make drivers aware of the higher speed of e-bikes, and give e-bikes a distinct appearance. Goal of this experiment was to investigate the effects of such a unique appearance, coupled with clear instructions about the capabilities of ebikes, on gap acceptance and TTA estimates. Participants were presented with video sequences of approaching cyclists clearly identifiable as either riding a conventional bicycle or e-bike, and were required to either indicate the smallest acceptable gap for a left turn in front of the cyclist, or to estimate TTA in two different experimental blocks. The results showed no difference in accepted gap size between the two appearances of the cyclist, whereas there was a minor effect on TTA estimates. Overall, the results imply that simply informing other road users about e-bikes (in conjunction with a re-design that gives them a unique appearance), might not be sufficient to elicit a more conservative behavior

Recruitment of Activation Receptors at Inhibitory NK Cell Immune Synapses

Natural killer (NK) cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR) family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses

Decision-Model Estimation of the Age-Specific Disability Weight for Schistosomiasis Japonica: A Systematic Review of the Literature

Schistosomiasis is among the most prevalent parasitic infections worldwide. However, current Global Burden of Disease (GBD) disability-adjusted life year estimates indicate that its population-level impact is negligible. Recent studies suggest that GBD methodologies may significantly underestimate the burden of parasitic diseases, including schistosomiasis. Furthermore, strain-specific disability weights have not been established for schistosomiasis, and the magnitude of human disease burden due to Schistosoma japonicum remains controversial. We used a decision model to quantify an alternative disability weight estimate of the burden of human disease due to S. japonicum. We reviewed S. japonicum morbidity data, and constructed decision trees for all infected persons and two age-specific strata, <15 years (y) and ≥15 y. We conducted stochastic and probabilistic sensitivity analyses for each model. Infection with S. japonicum was associated with an average disability weight of 0.132, with age-specific disability weights of 0.098 (<15 y) and 0.186 (≥15 y). Re-estimated disability weights were seven to 46 times greater than current GBD measures; no simulations produced disability weight estimates lower than 0.009. Nutritional morbidities had the greatest contribution to the S. japonicum disability weight in the <15 y model, whereas major organ pathologies were the most critical variables in the older age group. GBD disability weights for schistosomiasis urgently need to be revised, and species-specific disability weights should be established. Even a marginal increase in current estimates would result in a substantial rise in the estimated global burden of schistosomiasis, and have considerable implications for public health prioritization and resource allocation for schistosomiasis research, monitoring, and control

Animation vielfältiger Prozeßabläufe mit Hilfe von Petri-Netzen

Petri-Netze und deren Erweiterungen stellen ein leistungsfähiges Instrument zur Model-lierung, Simulation und Animation von Systemen bzw. Prozessen dar. Mathematische Methoden die sowohl analytisch beschreibbar als auch graphisch darstellbar sind, wie z. B. Warteschlangenprobleme, Netzpläne, Suche optimaler Wege in Netzen bzw. Dynamische Optimierung, können mit Hilfe von Petri-Netzen modelliert werden. Werden Petri-Netze zur graphischen Darstellung gewählt, so können die Stellen (passive Knoten) mit Markenverweilzeiten sowie die Transitionen (aktive Knoten) mit Schaltzeiten belegt werden. Für die Zeiten sind deterministische bzw. stochastische Größen einsetzbar. Wird dem Gesamtnetz eine zentrale Uhr und den einzelnen zeitbehafteten Knoten jeweils eine lokale Uhr zugeordnet, so lassen sich die Prozeßabläufe mittels Animation sichtbar machen. Ein an der Professur Computergestützte Techniken entwickeltes Programmsystem dient zur Demonstration der einzelnen Probleme. In anschaulicher Weise kann damit das Ver-ständnis für die genannten Methoden sowie die mit ihrer Hilfe dargestellten Prozesse erleichtert werden

Campylobacter fetus Bacteremia Revealed by Cellulitis without Gastrointestinal Symptoms in the Context of Acquired Hypogammaglobulinemia: A Report of Three Cases

Campylobacter fetus bacteremia is rare and occurs mainly in patients with immunosuppression. This infection, which often involves secondary localizations has already been reported in some primary humoral immune deficiencies. We describe three cases of severe infection due to C. fetus with cellulitis at presentation, but without any gastrointestinal symptoms, occurring in patients with acquired hypogammaglobulinemia

Intérêt D’une Recherche De Thrombophilie Au Cours Des Thromboses De La Veine Porte Dans Un Service De Médecine Interne

Background: Many causes of portal vein thrombosis are described and most patients had a combination of local and systemic risk factors. In many studies, prtothombotic disorders investigations were conducted in various departments of haematologies and/or gastroenterology. In this study, we investigated the systemic risk factors associated or not to abdominal inflammation in a series of patients recruited in a department of Internal Medicine. Methods: We studied, retrospectively from 2005 to 2009, 21 cases of patients with portal vein thrombosis. Patients with cancer are not included in this study. Results: We reported 21 patients with portal vein thrombosis: 8 males (43%) and 13 females (57%). The average age of patients was 46, 6 years (20; 59). Eight (8) patients had abdominal inflammatory pathology and 21 (100%) patients had systemic prothrombotic factors. This etiologic investigation is rentable because in 18 cases, abdominal inflammation and/or prothombotic disorders are diagnosed. This diagnostic, however, can permit to discuss a specific management. Conclusion: Extensive investigation of prothrombotic disorders is necessary in portal vein thrombosis, although if local abdominal inflammation exist

POS1247 CLINICAL FEATURES AND OUTCOMES OF COVID-19 IN PATIENTS WITH IGG4-RELATED DISEASE. A COLLABORATIVE EUROPEAN MULTI-CENTRE STUDY

Background:Coronavirus disease 2019 (COVID-19) is a pandemic-spread systemic infectious disease with prominent respiratory manifestations and significant associated morbidity and mortality. Elderly people are most significantly affected with mortality ranging from 2.4% (age 60-69) to 19.6% (age>80) in European Countries. The prevalence of COVID-19 and of its complications in patients with immune-mediated disorders, remains unclear. The frequency and impact of COVID-19 on patients with IgG4-related diease (IgG4-RD), many of whom are on concurrent immunosuppression has not been addressed.Objectives:To assess the epidemiological and clinical relevance of COVID-19 in patients with IgG4-RD.Methods:This is a multi-centre retrospective observational study of IgG4-RD patients from France, Italy, Spain and the United Kingdom. Demographics, comorbidities, IgG4-RD features, current and past treatment along with COVID-19-suggestive symptoms and COVID-19 diagnoses from February 2020 to January 2021 were recorded by means of direct or phone interviews. Patients with reverse-transcriptase polymerase chain reaction-confirmed (cCOVID) or presumed COVID-19 based on clinical, serological or imaging features (pCOVID) were pooled for analysis (totCOVID) and compared to patients who were not diagnosed with COVID-19. Inter-group comparison of categorical and quantitative variables were performed by using the chi-square test with Fisher's correction and the Mann-Whitney's test respectively. Data are expressed as median (interquartile range) unless otherwise specified.Results:A total of 305 patients [71% males, median age 64 (54-74) years] were studied. Pancreato-biliary disease was the most frequently observed IgG4-RD phenotype (39%). Fifty-one percent of patients were taking corticosteroids at time of interview and 30% were on biological or conventional immunosuppressants. Thirty-two totCOVID cases (23 cCOVID, nine pCOVID) were identified: 11/32 were hospitalised, two needed intensive care and four (13%; 3/4 aged >80 years) died. Having one or more infected family members was a risk factor for COVID-19 in patients with IgG4-RD (OR=19.9; p20mg) or rituximab administration.Conclusion:The prevalence and course of COVID-19 in IgG4-RD patients are similar to those of the general population of the same age, with no evident impact of disease- or treatment-related factors to the basal infectious risk. Effective public health countermeasures might be beneficial for patients with IgG4RD.References:[1]European Centre for Disease Prevention and Control (ECDC): https://covid19-surveillance-report.ecdc.europa.eu/[2]Yang H, Ann Rheum Dis, 2021Disclosure of Interests:Giuseppe Alvise Ramirez: None declared, Marco Lanzillotta: None declared, Mikael Ebbo: None declared, Andreu Fernandez-Codina Consultant of: consulting fees from Atheneum Consulting, Gaia Mancuso: None declared, Fernando Martínez-Valle: None declared, Olimpia Orozco-Galvez: None declared, Nicolas Schleinitz: None declared, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, BristolMyers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline,Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI, Emma L. Culver: None declared, Emanuel Della Torre: None declare