Hsa-miR-21-5p reflects synovitis and tenosynovitis components of musculoskeletal ultrasonography Seven-joint scores in rheumatoid arthritis disease and predicts the disease flare.

Rheumatoid arthritis (RA) is characterized by progressive joint destruction with subsequent serious disability. Objective biomarkers of RA course progression are lacking, which necessitates the discovery of activity indicators and predictors of the disease outcome. Musculoskeletal Ultrasound Seven-joint Score (MSUS7) is proposed as a reliable technique to evaluate radiographic RA progression. Homo sapiens-microRNA-21-5p (hsa-miR-21-5p) plays an important role during joint remodeling and the pro-inflammatory process driving RA progression. We aimed to evaluate plasma hsa-miR-21-5p as a noninvasive RA activity biomarker and to investigate if hsa-miR-21-5p is linked to MSUS7 components in the context of RA activity. This cross-sectional study included 71 RA patients classified into inactive (n = 36) and active (n = 35) groups according to the Disease Activity Score 28-joint count with ESR (DAS28-ESR). Joints were assessed by MSUS7. Gray-scale ultrasound (GSUS) and power Doppler ultrasound (PDUS) were used to rate the synovitis, tenosynovitis, and erosion in the joints. Plasma hsa-miR-21-5p expression was measured by real-time PCR. The absolute count of regulatory T cell (Treg) was calculated after Treg frequency was assessed by flow cytometry. Results: Hsa-miR-21 expression was significantly up-regulated in the active RA group with a median fold change of 51.6 in comparison to the inactive cases with a median fold change of 7.7 (p < 0.001). Hsa-miR-21-5p was positively correlated with DAS28-ESR, C reactive protein (CRP), and rheumatoid factor (r = 0.7, p < 0.001, r = 0. 0.6, p < 0.001, and r = 0.4, p = 0.002, respectively), while negatively correlated with Treg absolute count (r = -0.4, p < 0.001). Hsa-miR-21-5p levels were correlated with synovitis and tenosynovitis in GSUS (r = 0.4, p < 0.001, r = 0.3, p = 0.025, respectively) and in PDUS (r = 0.5, p < 0.001 and 0.4, p = 0.001, respectively). The hsa-miR-21-5p accurately distinguished RA activity [AUC 0.933, 94.3% sensitivity, and 86.1% specificity]. Logistic regression analysis revealed hsa-miR-21-5p as an independent predictor for RA flare (OR = 1.228, p = 0.004). Hsa-miR-21-5p was linked to synovitis and tenosynovitis components of the MSUS7. Up-regulated hsa-miR-21-5p can be utilized as a predictor for RA disease flare.

Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma.

PURPOSE: The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC. METHODS: Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC (n = 40), LC with HCC (n = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression. RESULTS: Hsa-miR-21-5p correlated with intermediate monocytes (r = 0.30, p = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes (r = - 0.316, p = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders. CONCLUSION: Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved.

Gender sensitivity in career mentoring - a project report from the Medical Faculty of Leipzig University.

Objective: The elective subject "career management for medical students" is presented as an example of teaching gender sensitivity issues among medical studies at Leipzig University. The project report shows the interim results of promoting gender-sensitive teaching at the Medical Faculty of Leipzig University, as well as the elective's contribution to the development of gender sensitivity at the entire university. Method: Project Description and Results show the organization/procedure, participants and detailed contents of the elective since it began in Winter Term 2010/11. The research examines the elective's mandate at the Medical Faculty and beyond, i.e. by comparing with the efforts of other universities. Results: The elective is the first subject for credit within the clinical curriculum of medical studies at Leipzig University that connects the topics of gender sensitivity and career management. It creates a view of the specialties of medicine and research as they relate to gender, and also on the options of a medical career and touches the topic of gender equality. A faculty survey in the winter semester of 2011/12 reveals that nearly one third of the medical students want an extension of the curriculum around the topic of gender or even an independent subject "Gender Medicine". The elective is part of a cycle promoting gender equality at Leipzig University. Conclusion: The elective initiates and continues the implementation of gender-sensitive teaching at the Medical Faculty of Leipzig University. The management of the elective aims at the permanent establishment of the subject in the curriculum in order to encourage career ambitions early - especially for women.

Thorax, trachea, and lung ultrasonography in emergency and critical care medicine: assessment of an objective structured training concept.

Background and Study objective. Focused lung ultrasound (LUS) examinations are important tools in critical care medicine. There is evidence that LUS can be used for the detection of acute thoracic lesions. However, no validated training method is available. The goal of this study was to develop and assess an objective structured clinical examination (OSCE) curriculum for focused thorax, trachea, and lung ultrasound in emergency and critical care medicine (THOLUUSE). Methods. 39 trainees underwent a one-day training course in a prospective educational study, including lectures in sonoanatomy and -pathology of the thorax, case presentations, and hands-on training. Trainees' pre- and posttest performances were assessed by multiple choice questionnaires, visual perception tests by interpretation video clips, practical performance of LUS, and identification of specific ultrasound findings. Results. Trainees postcourse scores of correct MCQ answers increased from 56 ± 4% to 82 ± 2% (mean± SD; P < 0.001); visual perception skills increased from 54 ± 5% to 78 ± 3% (P < 0.001); practical ultrasound skills improved, and correct LUS was performed in 94%. Subgroup analysis revealed that learning success was independent from the trainees' previous ultrasound experience. Conclusions. THOLUUSE significantly improves theoretical and practical skills for the diagnosis of acute thoracic lesions. We propose to implement THOLUUSE in emergency medicine training.

A consensus statement on practical skills in medical school - a position paper by the GMA Committee on Practical Skills.

INTRODUCTION: Encouraged by the change in licensing regulations the practical professional skills in Germany received a higher priority and are taught in medical schools therefore increasingly. This created the need to standardize the process more and more. On the initiative of the German skills labs the German Medical Association Committee for practical skills was established and developed a competency-based catalogue of learning objectives, whose origin and structure is described here. Goal of the catalogue is to define the practical skills in undergraduate medical education and to give the medical schools a rational planning basis for the necessary resources to teach them. METHODS: Building on already existing German catalogues of learning objectives a multi-iterative process of condensation was performed, which corresponds to the development of S1 guidelines, in order to get a broad professional and political support. RESULTS: 289 different practical learning goals were identified and assigned to twelve different organ systems with three overlapping areas to other fields of expertise and one area of across organ system skills. They were three depths and three different chronological dimensions assigned and the objectives were matched with the Swiss and the Austrian equivalent. DISCUSSION: This consensus statement may provide the German faculties with a basis for planning the teaching of practical skills and is an important step towards a national standard of medical learning objectives. LOOKING AHEAD: The consensus statement may have a formative effect on the medical schools to teach practical skills and plan the resources accordingly.

Does the 23-valent pneumococcal vaccine protect cochlear implant recipients?

OBJECTIVES/HYPOTHESIS: The incidence of meningitis is increased in cochlear implant (CI) recipients. Besides malformations, immunological deficiencies are predisposing factors. Therefore, the immunological background of CI recipients and the immunogenicity of the recommended 23-valent pneumococcal polysaccharide vaccine (PPV-23) were investigated. STUDY DESIGN: Prospective study in a tertiary care referral center. METHODS: One hundred twenty CI recipients who were at least 5 years of age were vaccinated with PPV-23. Levels of immunoglobulins G, A, and M (IgG, IgA, and IgM, respectively) and IgG subclasses IgG1-IgG4 before vaccination and serum concentrations of antibodies against seven pneumococcal serotypes before and 4 weeks after vaccination were determined. The cohort was subdivided by patient age into groups A1 (5-8 y), A2 (8-12 y), and A3 (>12 y). RESULTS: Geometric mean concentrations of pneumococcal antibodies before vaccination were remarkably low in all three groups, emphasizing the importance of vaccination in this risk group. All groups showed a statistically significant increase in geometric mean concentrations after immunization. For group A1 compared with groups A2 and A3, response was limited, especially for serotypes 6B (geometric mean concentration, 1.71 microg/mL; P = .0007), 23F (geometric mean concentration, 2.28 microg/mL; P = .04), and 14 (geometric mean concentration, 3.98 microg/mL; P = .0004). The percentages of patients reaching the presumed protective threshold of at least 1 microg/mL pneumococcal antibody concentration were at least 71.1% in group A1, 93.8% in group A2, and 90.5% in group A3. This raises the question of whether PPV-23 evokes satisfying seroprotection in CI recipients younger than 8 years of age. CONCLUSION: With regard to the increased risk for bacterial meningitis, the authors recommend priming CI recipients younger than 8 years of age with pneumococcal conjugate vaccine followed by a PPV-23 booster.

Immunogenicity of pneumococcal vaccination of patients with cochlear implants.

BACKGROUND: Pneumococcal meningitis is a rare but potentially fatal complication of cochlear implantation. METHODS: A prospective study was conducted of the immunogenicity of pneumococcal vaccination in 174 patients with cochlear implants (CIs). The cohort was divided into groups of patients with impaired hearing due to meningitis (P(1)), cranial malformations (P(2)), or an unknown cause (P(3)) and was stratified by age as follows: <2 years (A(1)), 2-5 years (A(2)), and >5 years (A(3)). We determined immunoglobulin (Ig) levels for IgG subclasses 1-4 and serum concentrations of antibodies against pneumococci before and 4-6 weeks after vaccination. Group A(1) received the 7-valent pneumococcal conjugate vaccine (PCV-7), group A(2) received PCV-7 or the 23-valent pneumococcal polysaccharide vaccine (PPV-23), and group A(3) received PPV-23. RESULTS: IgG, IgM, and IgG1 levels were significantly lower in group P(1), compared with the other patient groups and with historic data for healthy control subjects, suggesting a decreased antibody response. Group P(1) had lower levels of pneumococcal antibodies, compared with groups P(2) and P(3) before vaccination (P<.05, pneumococcal serotypes 4 and 9V). Irrespective of the underlying condition, all patients showed a sufficient antibody response after 1 dose of vaccine. In children 2-5 years of age, PCV-7 was significantly more immunogenic than PPV-23. CONCLUSIONS: PCV-7 should be administered to all CI recipients younger than 6 years and older than 6 years who are at an increased risk for bacterial meningitis. CI recipients with a history of bacterial meningitis should undergo immunological evaluation.