Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) has been associated with tumour suppression in various cancers. However, its putative role in bladder cancer is completely unknown. Therefore, we initiated a study analysing ITIH5 expression as well as its prognostic and functional impact on human urothelial cancers (UCs). Expression analysis showed a clear down-regulation of ITIH5 mRNA in 61% (n = 45) of UCs, especially in muscle-invasive tumours (P < 0.001). ITIH5 loss in UCs was further evident on protein level (65.5%, n = 55) as detected by immunohistochemistry. DNA methylation analysis demonstrated tumour-specific ITIH5 promoter methylation in 50% of papillary none-invasive pTa (n = 30) and 68% of invasive (n = 28) UCs. Aberrant ITIH5 promoter methylation in bladder tumours was tightly linked (P < 0.001) with loss of ITIH5 mRNA expression, which was furthermore functionally confirmed by demethylation analysis in cell lines. Pyrosequencing analysis revealed that ITIH5 promoter hypermethylation was closely associated with progressive bladder cancers. Subsequently, a large cohort (n = 120) of clinically challenging pT1 high-grade UC was analysed for ITIH5 expression. Of clinical significance, we found an association between loss of ITIH5 expression and unfavourable prognosis of UC patients without distant metastasis at first diagnosis (recurrence-free survival; hazard ratio: 4.35, P = 0.048). Functionally, ITIH5 re-expression in human RT112 bladder cancer cells led to both suppression of cell migration and inhibition of colony spreading. Hence, we provide evidence that down-regulation of ITIH5 by aberrant DNA hypermethylation may provoke invasive phenotypes in human bladder cancer. Moreover, ITIH5 protein might become a prognostic biomarker for relapse risk stratification in high-grade UC patients.

The fixation of stable trochanteric femur fractures with RoSA in cadavers led to greater primary stability under cyclic load, with significant advantages with regard to stiffness, failure load, and rotational stability, compared with the SHS. A detrimental effect was its migration tendency, which began at 1800 N and occurred in the cranial direction. A meticulous insertion technique was a prerequisite to avoid iatrogenic perforation of the femoral head. Our results will have to be substantiated by further biomechanical and clinical trials using an optimized RoSA system.

Purpose To assess the use of peer-assisted learning (PAL) of complex manipulative motor skills with respect to gender in medical students. Methods In 2007-2010, 292 students in their 3rd and 4th years of medical school were randomly assigned to two groups [Staff group (SG), PAL group (PG)] led by either staff tutors or student-teachers (ST). The students were taught bimanual practical and diagnostic skills (course education module of eight separate lessons) as well as a general introduction to the theory of spinal manipulative therapy. In addition to qualitative data collection (Likert scale), evaluation was performed using a multiple-choice questionnaire in addition to an objective structured clinical examination (OSCE). Results Complex motor skills as well as palpatory diagnostic competencies could in fact be better taught through professionals than through ST (manipulative OSCE grades/ diagnostic OSCE score; SG vs. PG; male: P = 0.017/ P \ 0.001, female: P \ 0.001/P \ 0.001). The registration of theoretical knowledge showed equal results in students taught by staff or ST. In both teaching groups (SG: n = 147, PG: n = 145), no significant differences were observed between male and female students in matters of manipulative skills or theoretical knowledge. Diagnostic competencies were better in females than in males in the staff group (P = 0.041) Overall, students were more satisfied with the environment provided by professional teachers than by ST, though male students regarded the PAL system more suspiciously than their female counterparts. Conclusions The peer-assisted learning system does not seem to be generally qualified to transfer such complex spatiotemporal demands as spinal manipulative procedures.

BackgroundPosttranslational protein modifications are known to modulate key biological processes like proliferation and apoptosis. Accumulating evidence shows that ST6GAL1, an enzyme that catalyzes the transfer of sialic acid onto galactose-containing substrates, is aberrantly expressed in various cancers and may affect cell motility and invasion. This is the first study to describe ST6GAL1 expression and regulation in human bladder cancer.MethodsST6GAL1 mRNA expression levels in human cell lines (UROtsa, RT4, RT112 and J82) and tissue samples (n = 15 normal urothelium (NU), n = 13 papillary non-invasive tumors (pTa), n = 12 carcinoma in situ (CIS), n = 26 muscle invasive tumors (pT2-4)) were assessed using real-time PCR. In addition, ST6GAL1 protein expression was evaluated using immunohistochemistry. Promoter methylation analysis was performed using methylation-specific PCR (MSP) in cell lines (n = 4) and patient samples (n = 23 NU, n = 12 CIS, n = 29 pTa, n = 41 pT2-4). Epigenetic ST6GAL1 gene silencing was confirmed by in vitro demethylation of bladder cell lines. Data were validated by analysis of an independent bladder tumor data set (n = 184) based on The Cancer Genome Atlas (TCGA) portal.ResultsSemi-quantitative ST6GAL1 real-time PCR expression analysis showed two distinct trends: In muscle-invasive tumors ST6GAL1 expression was downregulation by 2.7-fold, while papillary non-invasive tumors showed an increased ST6GAL1 mRNA expression compared to normal urothelium. ST6GAL1 loss in muscle-invasive tumors was associated with increasing invasiveness. On the protein level, 69.2% (n = 45/65) of all tumors showed a weak ST6GAL1 protein staining (IRS ≤ 4) while 25.6% (16/65) exhibited a complete loss (IRS = 0) of ST6GAL1 protein. Tumor-specific DNA methylation of the ST6GAL1 promoter region was frequently found in pT2-4 tumors (53.6% (22/41)), whereas only 13.8% (4/29) of pTa tumors showed ST6GAL1 promoter methylation. Normal urothelium remained unmethylated. Importantly, we significantly revealed an inverse correlation between ST6GAL1 mRNA expression and ST6GAL1 promoter merthylation in primary bladder cancer. These findings were clearly verified by the TCGA public data set and in vitro demethylation assays functionally confirmed ST6GAL1 promoter methylation as a potential regulatory factor for ST6GAL1 gene silencing.ConclusionsOur study characterizes for the first time ST6GAL1 expression loss caused by aberrant ST6GAL1 promoter methylation potentially indicating a tumor suppressive role in bladder carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-901) contains supplementary material, which is available to authorized users.

The aim of the present study was to analyze the diagnostic accuracy of the commonly used provocative tests in the diagnosis of lateral epicondylitis (LE). Cozen's test, Mills test and Maudsley test are most widely used. Till date no studies have been reported on the diagnostic accuracy of these tests. Musculoskeletal ultrasonography serves as a gold standard tool in the diagnosis of LE. Thirty subjects participated in the study. Baseline measurements of pain severity, elbow joint mobility, hand grip strength and three provocative tests were recorded by the principal investigator. A second investigator accompanied the subjects for musculoskeletal ultrasonography who was blinded of the test results. The thickness of common extensor tendon, echo texture and lateral epicondyle bony contour was measured. The test results of the three provocative tests with ultrasonographic findings were analyzed. The sensitivity for Cozen's test, Maudsley test and Mills test was found to be 84%, 88% and 53% respectively. The specificity for Cozen's Maudsley and Mills test was found to be 0%, 0% and 100% respectively. Mills test showed significant area under receiver operator curve (ROC) i.e. (0.769), which explains that the test has good diagnostic accuracy. This validation study, concludes that Mills test has an excellent diagnostic value for ruling in LE.