Steuerelemente bei der Wanderung und Funktion dendritischer Zellen : funktionelle Untersuchungen zu CCR7, Sphingosin-1-Posphat und CD83

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clinical recommendations from the european society for sexual medicine exploring partner expectations satisfaction in male and phalloplasty cohorts the impact of penile length girth and implant type reservoir placement and the influence of comorbidities and social circumstances

Abstract Introduction To date, several aspects of inflatable penile prosthesis (IPP) surgical procedure have been poorly studied. Aim The aim of this study was to review the evidence associated with IPP implantation and provide clinical recommendations on behalf of the European Society for Sexual Medicine (ESSM). Overall, 130 peer-reviewed studies and systematic reviews, which were published from 2007−2018 in the English language, were included. Methods MEDLINE and EMBASE were searched for randomized clinical trials, meta-analyses, and open-label prospective and retrospective studies. Main Outcome Measure The panel provided statements exploring patients and partner expectations, satisfaction in male and phalloplasty cohorts, the impact of penile length, girth and implant type, reservoir placement, the influence of comorbidities, and social circumstances. Levels of evidence were provided according to the Oxford 2011 criteria and graded as for the Oxford Centre for Evidence-Based Medicine recommendations. Results In the preoperative setting, it is fundamental to identify and interact with difficult patients with the intention of enhancing the surgeon's ability to establish the surgeon-patient relationship, reduce physical and legal risk, as well as enhancing patient satisfaction. To address this need, the mnemonic Compulsive, Unrealistic, Revision, Surgeon Shopping, Entitled, Denial, and Psychiatric ("CURSED") has been suggested to identify patients who are at high risk of dissatisfaction. The current recommendations suggest improving glycemic control in patients with diabetes. Available evidence suggests evaluating transplant recipients with the criteria of Barry, consisting of stable graft function for >6 months, avoidance of intra-abdominal reservoir placement, and low-dose immunosuppression. HIV status does not represent a contraindication for surgery. Smoking, peripheral vascular disease, and hypertension may be associated with an increased risk of revision surgery. Patients with spinal cord injury may receive IPP. Patients aged ≥70 years, as well as obese patients, can be offered IPP. The IPP implantation can be performed in patients with stable Peyronie's disease. Ectopic high submuscular reservoir placement can be considered as an alternative method. Clinical Implications There is a relevant lack of high-level data and definite conclusions in certain areas remain difficult to draw. Strength & Limitations All studies have been evaluated by a panel of experts providing recommendations for clinical practice. Because of lack of sufficient prospective data, some of the included studies are retrospective and this could be stated as a limitation. Conclusion This ESSM position statement provides recommendations on optimization of patient outcome by patient selection, and individualized peri- and intra-operative management. ESSM encourages centers to collaborate and to create prospective, multicenter registries in order to address this topic of increasing importance. Osmonov D, Christopher AN, Blecher GA, et al. Clinical Recommendations from the European Society for Sexual Medicine Exploring Partner Expectations, Satisfaction in Male and Phalloplasty Cohorts, the Impact of Penile Length, Girth and Implant Type, Reservoir Placement, and the Influence of Comorbidities and Social Circumstances. J Sex Med 2019;XX:XXX–XXX

Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease

The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4+CD45RBhi cells, and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function

DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling

Dermal DC mobilization requires docking to CCL21 on lymphatic endotheliu

In Vitro and In Vivo Antagonism of a G Protein-Coupled Receptor (S1P3) with a Novel Blocking Monoclonal Antibody

Background: S1P 3 is a lipid-activated G protein-couple receptor (GPCR) that has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. Currently, there are no available high-affinity, subtypeselective drug compounds that can block activation of S1P3. We have developed a monoclonal antibody (7H9) that specifically recognizes S1P3 and acts as a functional antagonist. Methodology/Principal Findings: Specific binding of 7H9 was demonstrated by immunocytochemistry using cells that over-express individual members of the S1P receptor family. We show, in vitro, that 7H9 can inhibit the activation of S1P3mediated cellular processes, including arrestin translocation, receptor internalization, adenylate cyclase inhibiton, and calcium mobilization. We also demonstrate that 7H9 blocks activation of S1P3 in vivo, 1) by preventing lethality due to systemic inflammation, and 2) by altering the progression of breast tumor xenografts. Conclusions/Significance: We have developed the first-reported monoclonal antibody that selectively recognizes a lipidactivated GPCR and blocks functional activity. In addition to serving as a lead drug compound for the treatment of sepsi

Interrelationship between Dendritic Cell Trafficking and Francisella tularensis Dissemination following Airway Infection

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11bhigh/CD11cmed/autofluorescencelow DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria (∼75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment

Entwurf eines Planspiels zur Förderung des vernetzten Denkens in der Logistik

In dieser Arbeit wird zur Verbesserung der Logistikaus- und -weiterbildung ein Planspiel entwickelt. Dieses Planspiel "Logistisches Netzwerk" ist das Ergebnis der Synthese von Planspieltechnik und Wirkungsnetzen. Es verfolgt das Lernziel, den Umgang mit komplexen Entscheidungssituationen des Logistikers zu trainieren. Es ist als Ergänzung zu den konventionellen Unterrichtsmethoden ein geeignetes Instrument der Logistikaus- und -weiterbildung