High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding suggested the possibly that the complex, rather than the individual molecules, could support tumor progression. The expression of EpCAM, claudin-7, CO-029, and CD44v6 expression was evaluated in colorectal cancer (n = 104), liver metastasis (n = 66), and tumor-free colon and liver tissue. Coexpression and complex formation of the molecules was correlated with clinical variables and apoptosis resistance. EpCAM, claudin-7, CO-029, and CD44v6 expression was up-regulated in colon cancer and liver metastasis. Expression of the four molecules did not correlate with tumor staging and grading. However, coexpression inversely correlated with disease-free survival. Coexpression was accompanied by complex formation and recruitment into tetraspanin-enriched membrane microdomains (TEM). Claudin-7 contributes to complex formation inasmuch as in the absence of claudin-7, EpCAM hardly associates with CO-029 and CD44v6 and is not recruited into TEMs. Notably, colorectal cancer lines that expressed the EpCAM/claudin-7/CO-029/CD44v6 complex displayed a higher degree of apoptosis resistance than lines devoid of any one of the four molecules. Expression of EpCAM, claudin-7, CO-029, and CD44v6 by themselves cannot be considered as prognostic markers in colorectal cancer. However, claudin-7 -associated EpCAM is recruited into TEM and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation. (Mol Cancer Res 2007;5(6):553 -67)

Summary Background Many unicellular organisms age: as time passes, they divide more slowly and ultimately die. In budding yeast, asymmetric segregation of cellular damage results in aging mother cells and rejuvenated daughters. We hypothesize that the organisms in which this asymmetry is lacking, or can be modulated, may not undergo aging. Results We performed a complete pedigree analysis of microcolonies of the fission yeast Schizosaccharomyces pombe growing from a single cell. When cells were grown under favorable conditions, none of the lineages exhibited aging, which is defined as a consecutive increase in division time and increased death probability. Under favorable conditions, few cells died, and their death was random and sudden rather than following a gradual increase in division time. Cell death correlated with the inheritance of Hsp104-associated protein aggregates. After stress, the cells that inherited large aggregates aged, showing a consecutive increase in division time and an increased death probability. Their sisters, who inherited little or no aggregates, did not age. Conclusions We conclude that S. pombe does not age under favorable growth conditions, but does so under stress. This transition appears to be passive rather than active and results from the formation of a single large aggregate, which segregates asymmetrically at the subsequent cell division. We argue that this damage-induced asymmetric segregation has evolved to sacrifice some cells so that others may survive unscathed after severe environmental stresses.

EpCAM has been described as a therapeutically relevant tumor marker. We noted an interaction between EpCAM and the tight junction protein claudin-7 and here explored the nature of this interaction and its effect on EpCAM-mediated functions. The interaction between EpCAM and claudin-7 was defined in HEK293 cells transfected with rat claudin-7 and EpCAM cDNA. Deletions of the epidermal growth factor -like and the thyroglobin repeat domains of EpCAM or the cytoplasmic domain of EpCAM or claudin-7 did not prevent the EpCAM-claudin-7 association. A chimeric EpCAM molecule with an exchange of the cytoplasmic and transmembrane domains and an EpCAM molecule with point mutations in an AxxxG motif in the transmembrane region do not associate with claudin-7. HEK cells and the rat pancreatic tumor line BSp73AS, transfected with (mutated) EpCAM and claudin-7 cDNA, revealed that the association of both molecules severely alters the functional activity of EpCAM. Claudin-7 -associated

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The current choice of digital teaching and learning formats in medicine is very heterogeneous. In addition to the widely used classical static formats, social communication tools, audio/video-based media, interactive formats, and electronic testing systems enrich the learning environment.For medical students, the private use of digital media is not necessarily linked to their meaningful use in the study. Many gain their experience of digital learning in the sense of "assessment drives learning", especially by taking online exams in a passive, consuming role. About half of all medical students can be referred to as "e-examinees" whose handling of digital learning is primarily focused on online exam preparation. Essentially, they do not actively influence their digital environment. Only a quarter can be identified as a "digital all-rounder", who compiles their individual learning portfolio from the broad range of digital media.At present, the use of digital media is not yet an integral and comprehensive component of the teaching framework of medical studies in Germany, but is rather used in the sense of a punctual teaching enrichment. Current trends in digital teaching and learning offerings are mobile, interactive, and personalized platforms as well as increasing the relevance of learning platforms. Furthermore, didactical concepts targeting the changed learning habits of the students are more successful regarding the acceptance and learning outcomes. In addition, digitalization is currently gaining importance as a component in the medical school curricula.

BackgroundHealth apps for the screening and diagnosis of mental disorders have emerged in recent years on various levels (eg, patients, practitioners, and public health system). However, the diagnostic quality of these apps has not been (sufficiently) tested so far.ObjectiveThe objective of this pilot study was to investigate the diagnostic quality of a health app for a broad spectrum of mental disorders and its dependency on expert knowledge.MethodsTwo psychotherapists, two psychology students, and two laypersons each read 20 case vignettes with a broad spectrum of mental disorders. They used a health app (Ada—Your Health Guide) to get a diagnosis by entering the symptoms. Interrater reliabilities were computed between the diagnoses of the case vignettes and the results of the app for each user group.ResultsOverall, there was a moderate diagnostic agreement (kappa=0.64) between the results of the app and the case vignettes for mental disorders in adulthood and a low diagnostic agreement (kappa=0.40) for mental disorders in childhood and adolescence. When psychotherapists applied the app, there was a good diagnostic agreement (kappa=0.78) regarding mental disorders in adulthood. The diagnostic agreement was moderate (kappa=0.55/0.60) for students and laypersons. For mental disorders in childhood and adolescence, a moderate diagnostic quality was found when psychotherapists (kappa=0.53) and students (kappa=0.41) used the app, whereas the quality was low for laypersons (kappa=0.29). On average, the app required 34 questions to be answered and 7 min to complete.ConclusionsThe health app investigated here can represent an efficient diagnostic screening or help function for mental disorders in adulthood and has the potential to support especially diagnosticians in their work in various ways. The results of this pilot study provide a first indication that the diagnostic accuracy is user dependent and improvements in the app are needed especially for mental disorders in childhood and adolescence.

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IntroductionPrevious studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts (MFs) is significantly increased in stiff joint capsules, indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs' function has been well defined for different diseases associated with tissue fibrosis, the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown.MethodsIn this study, we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) on cellular functions of human joint capsule MFs. MFs were challenged with different concentrations of TNF-α with or without both its specifically inactivating antibody infliximab (IFX) and cyclooxygenase-2 (COX2) inhibitor diclofenac. Cell proliferation, gene expression of both alpha-smooth muscle actin (α-SMA) and collagen type I, the synthesis of prostaglandin derivates E2, F1A, and F2A, as well as the ability to contract the extracellular matrix were assayed in monolayers and in a three-dimensional collagen gel contraction model. The α-SMA and COX2 protein expressions were evaluated by immunofluorescence staining and Western blot analysis.ResultsThe results indicate that TNF-α promotes cell viability and proliferation of MFs, but significantly inhibits the contraction of the extracellular matrix in a dose-dependent manner. This effect was associated with downregulation of α-SMA and collagen type I by TNF-α application. Furthermore, we found a significant time-dependent upregulation of prostaglandin E2 synthesis upon TNF-α treatment. The effect of TNF-α on COX2-positive MFs could be specifically prevented by IFX and partially reduced by the COX2 inhibitor diclofenac.ConclusionsOur results provide evidence that TNF-α specifically modulates the function of MFs through regulation of prostaglandin E2 synthesis and therefore may play a crucial role in the pathogenesis of joint capsule contractures.