Search

This article introduces the university initiative “Heidelberg Clinical Standards”, a project that provides medical students with standardized clinical-practical and communication skills using training videos and manuals. Medical students from more than 20 medical faculties in Germany, Austria, and Switzerland can access the manuals’ e-versions and the corresponding training videos via our e-learning platform. Accordingly, the Heidelberg teaching and examination standards have become an important reference for teaching clinical practical skills to medical students in German-speaking countries.

Background: Before foreign language questionnaires, such as patient reported outcome measures (PROMs), can be scientifically used in the national language, guideline-based translation, cultural adaptation and comprehensive verification of their validity and reliability are needed. The aim of this study was to assess the psychometric properties of the German version of the LCI-5 (LCI-5-D) on a sample of people with lower limb amputation (LLA)., Methods: The LCI-5 was translated into German (LCI-5-D) based on the ISPOR guidelines for cross-cultural adaptation following pilot testing. The final LCI-5-D was administered to n = 52 lower limb amputees in order to determine the validity and reliability of both the total score and the subscores ("basic items" and "advanced items"). Internal consistency (Cronbach's alpha), test-retest reliability (ICC2,1), standard error of the mean (SEM), minimal detectable change (MDC), item-to-total correlation, and item-to-subscale correlation were calculated. Floor and ceiling effects were checked. For construct validity, the Rivermead Mobility Index (RMI) and timed up and go (TUG) test were correlated, and differences of defined subgroups (amputation height and prosthesis user type) were calculated., Results: On average, the score of the LCI-5-D was 40.13 ± 16.64 points. High ceiling effects were present for the subscale "basic items" (57.7% maximum score). Internal consistency showed excellent results (Cronbach's α = 0.97). A strong correlation to the RMI (r = 0.863; p < 0.001) and to the TUG (r = - 0.714; p < 0.001) demonstrated construct validity. Test-rest reliability was measured after an averaged time span of 5.3 ± 2.47 days and resulted in very high reliability [ICC (2,1) = 0.97; p < 0.001]. MDC was 7.57 points for the total score., Conclusion: The LCI-5-D is a valid and reliable PROM for measuring mobility with prostheses in German-speaking lower limb amputees, which is rather suitable for people with low to moderate mobility abilities. It can be used in a German-speaking population., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: The personality traits of emergency physicians are infrequently studied, though interest in physician wellness is increasing. The objective of this study is to acquire pilot data about the amount of grit, anxiety, and stress in emergency physicians using established psychological survey instruments, and to examine their associations of each of these traits with each other., Methods: Thirty-six emergency medicine resident and attending physicians from an urban academic medical center consented for enrollment. Participants were administered the Duckworth 12-point Grit Scale, the State-Trait Anxiety Inventory (STAI), and the Perceived Stress Scale (PSS), which measure grit, anxiousness, and perceived stress, respectively. These are the gold standard psychological instruments for each of their areas. We analyzed the results with descriptive statistics, Spearman correlations, and linear regression., Results: Nineteen residents and 17 attending physicians completed the surveys during the first quarter of a new academic year. The mean grit score was 3.7 (95% CI 3.5-3.8, SD: 0.56), the mean trait-anxiety score was 32.61 (95% CI 30.15-35.07, SD: 7.26), and the mean PSS score was 12.28 (95% CI 10.58-13.97, SD: 4.99). Only trait-anxiety and perceived stress were significantly correlated (Spearman's rho: 0.70, p<0.01)., Conclusions: In this pilot study at a single institution, emergency physicians demonstrated a range of grit, trait-anxiety, and perceived stress. Trait-anxiety and stress were strongly associated, and individuals who were more anxious reported more stress. Levels of grit were not associated with trait-anxiety. These psychological concepts should be studied further as they relate to the function and health of emergency medicine providers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

For decades, researchers have been developing a range of promising strategies in bone tissue engineering with the aim of producing a significant clinical benefit over existing therapies. However, a major problem concerns the traditional use of xenogeneic substances for the expansion of cells, which complicates direct clinical transfer. The study's aim was to establish a totally autologous sheep model as a basis for further preclinical studies and future clinical application. Ovine mesenchymal stromal cells (MSC) were cultivated in different concentrations (0%, 2%, 5%, 10%, and 25%) of either autologous serum (AS) or fetal calf serum (FCS). With an increase of serum concentration, enhanced metabolic activity and proliferation could be observed. There were minor differences between MSC cultivated in AS or FCS, comparing gene and protein expression of osteogenic and stem cell markers, morphology, and osteogenic differentiation. MSC implanted subcutaneously in the sheep model, together with a nanostructured bone substitute, either in stable block or moldable putty form, induced similar vascularization and remodeling of the bone substitute irrespective of cultivation of MSC in AS or FCS and osteogenic differentiation. The bone substitute in block form together with MSC proved particularly advantageous in the induction of ectopic bone formation compared to the cell-free control and putty form. It could be demonstrated that AS is suitable for replacement of FCS for cultivation of ovine MSC for bone tissue engineering purposes. Substantial progress has been made in the development of a strictly xenogeneic-free preclinical animal model to bring future clinical application of bone tissue engineering strategies within reach.

The aim of the present prospective observational study was to assess uptake and success of hepatitis C virus (HCV) treatment among a group of former and current injection drug users with chronic HCV infection at the Street Health Centre in Kingston, Ontario. The Street Health Centre offers hepatitis C education, assessment and treatment within a multidisciplinary, integrated and collaborative treatment model of care delivered by primary care professionals. The study enrolled a convenience sample of 34 patients. Seventy per cent of study patients had no postsecondary education, 85% were unemployed and one-third were unstably housed. A majority of study patients self-reported mental health problems. Of the 14 patients who initiated antiviral treatment in the study period, eight (57%) achieved sustained virological response. Regardless of virological outcome, patients who initiated treatment showed positive trends toward increased social and psychiatric stability, and decreases in high-risk behaviours. These results suggest that not only is successful treatment of chronic HCV infection in current and former injection drug users with concurrent psychiatric disorders possible, but the benefits of such treatment delivered in a community-based, multidisciplinary, primary care model may extend beyond narrowly defined virological outcomes.

The regulation of chondrocytes in osteoarthritic cartilage and the expression of specific gene products by these cells during early-onset and late-stage osteoarthritis are not well characterized. With the introduction of cDNA array technology, the measurement of thousands of different genes in one small tissue sample can be carried out. Interpretation of gene expression analyses in articular cartilage is aided by the fact that this tissue contains only one cell type in both normal and diseased conditions. However, care has to be taken not to over- and misinterpret results, and some major challenges must be overcome in order to utilize the potential of this technology properly in the field of osteoarthritis.

Objective: Osteoarthritic (OA) cartilage destruction depends on collagen- and aggrecan-degrading proteases such as collagenases (MMP-1 and MMP-13), stromelysin (MMP-3), MMP-14, as well as the so-called aggrecanases (ADAM-TS4 and ADAM-TS5). In this study, we tried to clarify whether these proteases are expressed in vivo in human normal and OA cartilage (and whether they are up-regulated or down-regulated during the disease process) and in interleukin-1beta (IL-1beta)-stimulated chondrocytes in vitro., Methods: Quantitative polymerase chain reaction assays were developed and performed on RNA isolated directly from normal and degenerative cartilage tissue as well as from primary human articular chondrocytes cultured with and without IL-1beta., Results: In vivo, MMP-1 was detectable only at very low levels in any condition. MMP-13 expression was low in normal and early degenerative cartilage but was strongly up-regulated in late-stage OA specimens. MMP-1 and MMP-13 were expressed much higher in vitro than in vivo and were up-regulated by IL-1beta. Among all proteases, MMP-3 was by far the most strongly expressed, although it was strongly down-regulated in late-stage OA specimens. Expression of MMP-3 was higher in vitro than in vivo and was up-regulated by IL-1beta. ADAM-TS5 and MMP-14 were expressed in all sample groups. Expression of ADAM-TS4 was very low in vivo and was induced in vitro after stimulation by IL-1beta., Conclusion: Our expression data clearly support MMP-13 as the major collagenase in OA cartilage. The most strongly expressed aggrecanase was ADAM-TS5. ADAM-TS4 was expressed only at a very low level in normal cartilage and was only slightly up-regulated in OA cartilage, casting doubt on this enzyme being the relevant aggrecanase of articular cartilage. Results of our study show that expression of many enzymes is significantly different in vitro and in vivo and suggest that IL-1beta stimulation of articular chondrocytes might not be a good model for the matrix catabolism in OA cartilage.

ADP-ribosylation factor (ARF) GTPases and their regulatory proteins have been implicated in the control of diverse biological functions. Two main classes of positive regulatory elements for ARF have been discovered so far: the large Sec7/Gea and the small cytohesin/ARNO families, respectively. These proteins harbor guanine-nucleotide-exchange factor (GEF) activity exerted by the common Sec7 domain. The availability of a specific inhibitor, the fungal metabolite brefeldin A, has enabled documentation of the involvement of the large GEFs in vesicle transport. However, because of the lack of such tools, the biological roles of the small GEFs have remained controversial. Here, we have selected a series of RNA aptamers that specifically recognize the Sec7 domain of cytohesin 1. Some aptamers inhibit guanine-nucleotide exchange on ARF1, thereby preventing ARF activation in vitro. Among them, aptamer M69 exhibited unexpected specificity for the small GEFs, because it does not interact with or inhibit the GEF activity of the related Gea2-Sec7 domain, a member of the class of large GEFs. The inhibitory effect demonstrated in vitro clearly is observed as well in vivo, based on the finding that M69 produces similar results as a dominant-negative, GEF-deficient mutant of cytohesin 1: when expressed in the cytoplasm of T-cells, M69 reduces stimulated adhesion to intercellular adhesion molecule-1 and results in a dramatic reorganization of F-actin distribution. These highly specific cellular effects suggest that the ARF-GEF activity of cytohesin 1 plays an important role in cytoskeletal remodeling events of lymphoid cells.

The induction of a transformed cellular phenotype by viruses requires the modulation of signaling pathways through viral proteins. We show here that the phenotypic changes induced by the kaposin A protein of human herpesvirus 8 are mediated through its direct interaction with cytohesin-1, a guanine nucleotide exchange factor for ARF GTPases and regulator of integrin-mediated cell adhesion. Focus formation, stress fiber dissolution, and activation of the ERK-1/2 MAP kinase signal cascade were reverted by the cytohesin-1 E157K mutant, which is deficient in catalyzing guanine nucleotide exchange. Furthermore, liposome-embedded kaposin A specifically stimulates cytohesin-1 dependent GTP binding of myristoylated ARF1 in vitro. These results suggest a previously unknown involvement of ARF GTPases in the control of cellular functions by herpesviruses.

ADP-ribosylation factors (ARFs) are small Ras-like GTPases which play important roles in intracellular vesicle transport and in the remodeling of the actin cytoskeleton. Guanine nucleotide exchange factors (GEFs) for ARFs have recently been identified. One of them, cytohesin-1, a 47-kDa cytoplasmic protein acts as an inside-out signaling molecule and regulates binding of the beta2 integrin leukocyte function antigen 1 (LFA-1) to its ligand intercellular adhesion molecule 1 (ICAM-1). In this study, we address the regulation of the GEF activity of cytohesin-1 by phosphoinositides, using mammalian expression of functional ARF-Ig chimeras. The fusion proteins, which can be quantitatively immunoprecipitated on protein A-Sepharose, target to the expected intracellular compartments, and they are readily induced to bind GTP in vitro. We show that both ARF1-Ig and ARF6-Ig chimeras are activated in vitro by cytohesin-1. However, GEF activity towards ARF6 is strongly suppressed by phosphatidylinositol-(3,4,5)-trisphosphate (PtdInsP3). In contrast, cytohesin-1-dependent GTP binding of ARF1 is significantly enhanced by PtdInsP3. We conclude that the membrane phospholipid PtdInsP3 determines the specificity of the GEF activity of cytohesin-1.