A 'minimal core curriculum' for Family Medicine in undergraduate medical education: a European Delphi survey among EURACT representatives.

Family Medicine/General Practice (FM/GP) has not developed in a similar way worldwide. In countries that are not primary care oriented, the discipline of FM/GP may be less developed because this is not a career option for medical graduates. In such a situation, FM/GP will not be regarded as a required clinical experience during medical school.To define the 'minimal requirements' or 'minimal core content' for a clerkship in FM/GP of very short duration, i.e. a basic curriculum for a clinical rotation in FM/GP, taking into account that in some European countries the time allocated for this rotation may not exceed one week.The Delphi method was used. The study group was composed of 40 family physicians and medical educators who act as national representatives of all European countries-plus Israel-in the Council of the European Academy of Teachers in General Practice and Family Medicine (EURACT). The representatives are elected among the EURACT members in their country.After three Delphi rounds we obtained a consensual list of 15 themes regarded by the respondents as the most important to be included in a minimal core curriculum for FM/GP in undergraduate medical education.This list may be useful for teachers and institutions that are about to introduce GP/FM as a new topic in their medical faculty, having only limited time available for the course. They will be able to focus on topics chosen by a European expert panel as being the most important in such a situation

Cerebral and Extracranial Neurodegeneration are Strongly Coupled in Parkinson’s Disease

In idiopathic Parkinson’s disease (PD), a generalized Lewy body type-degeneration in the brain as well as extracranial organs was identified. It is unclear, whether cerebral and extracranial Lewy body type-degeneration in PD are coupled or not. To address this question, cerebral [123I]FP-CIT SPECT – to quantify cerebral nigrostriatal dopaminergic degeneration – and myocardial [123I]MIBG scintigraphy – to quantify extracranial myocardial sympathetic degeneration – were performed in 95 PD patients and 20 healthy controls. At each Hoehn and Yahr stage separately, myocardial MIBG uptake correlated significantly with striatal FP-CIT uptake. No such correlation was found in the controls. Cerebral and extracranial Lewy body type-degeneration in PD do not develop independently from each other but develop in a strongly coupled manner. Obviously cerebral and extracranial changes are driven by at least similar pathomechanisms. Our findings in controls contradict a physiological correlation between nigrostriatal dopaminergic and myocardial sympathetic function

Covalent Adaptable Microstructures via Combining Two‐Photon Laser Printing and Alkoxyamine Chemistry: Toward Living 3D Microstructures

Manufacturing programmable materials, whose mechanical properties can be adapted on demand, is highly desired for their application in areas ranging from robotics, to biomedicine, or microfluidics. Herein, the inclusion of dynamic and living bonds, such as alkoxyamines, in a printable formulation suitable for two-photon 3D laser printing is exploited. On one hand, taking advantage of the dynamic covalent character of alkoxyamines, the nitroxide exchange reaction is investigated. As a consequence, a reduction of the Young´s Modulus by 50%, is measured by nanoindentation. On the other hand, due to its “living” characteristic, the chain extension becomes possible via nitroxide mediated polymerization. In particular, living nitroxide mediated polymerization of styrene results not only in a dramatic increase of the volume (≈8 times) of the 3D printed microstructure but also an increase of the Young\u27s Modulus by two orders of magnitude (from 14 MPa to 2.7 GPa), while maintaining the shape including fine structural details. Thus, the approach introduces a new dimension by enabling to create microstructures with dynamically tunable size and mechanical properties

Characterization of exoplanets from their formation I: Models of combined planet formation and evolution

A first characterization of many exoplanets has recently been achieved by the observational determination of their radius. For some planets, a measurement of the luminosity has also been possible, with many more directly imaged planets expected in the future. The statistical characterization of exoplanets through their mass-radius and mass-luminosity diagram is thus becoming possible. This is for planet formation and evolution theory of similar importance as the mass-distance diagram. Our aim in this and a companion paper is to extend our formation model into a coupled formation and evolution model. We want to calculate in a self-consistent way all basic characteristics (M,a,R,L) of a planet and use the model for population synthesis calculations. Here we show how we solve the structure equations describing the gaseous envelope not only during the early formation phase, but also during gas runaway accretion, and during the evolutionary phase at constant mass on Gyr timescales. We then study the in situ formation and evolution of Jupiter, the mass-radius relationship of giants, the influence of the core mass on the radius and the luminosity both in the "hot start" and the "cold start" scenario. We put special emphasis on the comparison with other models. We find that our results agree very well with those of more complex models, despite a number of simplifications. The upgraded model yields the most important characteristics of a planet from its beginning as a seed embryo to a Gyr old planet. This is the case for all planets in a synthetic planetary population. Therefore, we can now use self-consistently the statistical constraints coming from all major observational techniques. This is important in a time where different techniques yield constraints on very diverse sub-populations of planets, and where its is challenging to put all these constraints together in one coherent picture.Comment: Accepted to A&A. Identical as v1 except for additional online data reference and corrected typos. 23 pages, 11 figure

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool

Exposure to aircraft and road traffic noise and associations with heart disease and stroke in six European countries: a cross-sectional study

This work was supported by the Economic and Social Research Council (grant ES/F038763/1) with additional funding from the European Network for Noise and Health (ENNAH, EU FP7 grant number 226442)