High intra- and inter-rater chance variation of the movement assessment battery for children 2, ageband 2

The aim of the present study was to evaluate the intra- and inter-tester reliability of the movement assessment battery for children – second edition (MABC-2), ageband 2. We wanted to analyze the collected data, with adequate statistical methods, to provide relevant recommendations for physical therapists who are interpreting changes in the context of daily clinical practice. Forty-five healthy children, 23 girls and 22 boys with a mean age of 8.7 ± 0.7 years, participated in the study, the inter-tester procedures were performed the same day and the intra-tester procedures within a one to two week interval. The statistical methods used were intra-class correlation coefficient (ICC), standard error of measurement (SEM), and smallest detectable change (SDC).The children had no failed items during the tests. The ICC values ranged from 0.23 to 0.76. The items “treading lace” and “one-board balance” showed the highest measurement errors both for the intra- and inter-rater reliability. The SDC_90% values were 9.7 and 18.5 for the intra- and inter-rater reliability, respectively. The present study showed high intra- and inter-rater chance variation MABC-2, ageband 2. A change of more than ±9.7 and ±18.5 on the total test score (TTS) should be required to state (with a 90% confidence) that a real change in a single individual has occurred, for intra- and inter-rater testing, respectively. These findings may indicate that the MABC-2 might be more suitable for diagnostic or clinical decision making purposes, than for evaluation of change over time.     

Implications of caries diagnostic strategies for clinical management decisions

Baelum V, Hintze H, Wenzel A, Danielsen B, Nyvad B. Implications of caries diagnostic strategies for clinical management decisions. Community Dent Oral Epidemiol 2011. © 2011 John Wiley & Sons A/S Abstract – Objectives: In clinical practice, a visual–tactile caries examination is frequently supplemented by bitewing radiography. This study evaluated strategies for combining visual–tactile and radiographic caries detection methods and determined their implications for clinical management decisions in a low‐caries population. Methods: Each of four examiners independently examined preselected contacting interproximal surfaces in 53 dental students aged 20–37 years using a visual–tactile examination and bitewing radiography. The visual–tactile examination distinguished between noncavitated and cavitated lesions while the radiographic examination determined lesion depth. Direct inspection of the surfaces following tooth separation for the presence of cavitated or noncavitated lesions was the validation method. The true‐positive rate (i.e. the sensitivity) and the false‐positive rate (i.e. 1‐specificity) were calculated for each diagnostic strategy. Results: Visual–tactile examination provided a true‐positive rate of 34.2% and a false‐positive rate of 1.5% for the detection of a cavity. The combination of a visual–tactile and a radiographic examination using the lesion in dentin threshold for assuming cavitation had a true‐positive rate of 76.3% and a false‐positive rate of 8.2%. When diagnostic observations were translated into clinical management decisions using the rule that a noncavitated lesion should be treated nonoperatively and a cavitated lesion operatively, our results showed that the visual–tactile method alone was the superior strategy, resulting in most correct clinical management decisions and most correct decisions regarding the choice of treatment.     

MCS-18, a novel natural product isolated from Helleborus purpurascens, inhibits dendritic cell activation and prevents autoimmunity as shown in vivo using the EAE model

Here we report for the first time that MCS-18, a novel natural product isolated from Helleborus purpurascens, is able to inhibit the expression of typical molecules of mature dendritic cells (DC) such as CD80, CD86, and especially of CD83 subsequently leading to a clear and dose-dependent inhibition of the DC-mediated T-cell stimulation. Furthermore, MCS-18 impeded the formation of the typical DC/T-cell clusters, which are essential to induce potent immune responses. Interestingly, MCS-18 also inhibited CCR7 expression on DC which subsequently lead to a dose-dependent block of the CCL19-mediated DC migration. MCS-18 not only inhibited the DC-mediated T-cell stimulation but also the anti-CD3/anti-CD28-mediated T-cell stimulation. Strikingly, MCS-18 also strongly reduced the paralysis associated with the experimental autoimmune encephalomyelitis (EAE), which is a murine model for human multiple sclerosis, in a prophylactic as well as in a "real" therapeutic setting. Even when the EAE was induced for a second time, the MCS-18-treated animals were still protected, suggesting that MCS-18 induces a long-lasting suppressive effect. In addition, and very important for the potential practical application in humans, MCS-18 was also active when administered orally. MCS-18 treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In conclusion, using in vitro as well in vivo assays we were able to show that MCS-18 exerts a strong immunosuppressive activity with remarkable potential for the therapy of diseases characterized by a pathologically over-activated immune system.     

Einführung in die Vergangenheit,Gegenwart und Zukunft von Serious Games (for Health)

Background

(Serious) Games have been used for several educational and health-related interventions in health promotion and prevention. The use of games for serious purposes is strategy that dates back to the beginning of humankind.

Objectives

The following article will outline the evolutionary lines of Serious Games, starting with the first traces of games in human history up to the present. In-depth consideration of factors influencing the development of Serious Games in the past and present outline possible future developments and may lead to a better understanding of today’s developments.

Materials and methods

The present work is a narrative review and outlines the most important developments of games. The development of Serious Games for Health will be considered in more detail. The various influencing factors from the entertainment and military sectors are outlined as well as new technologies that change the use of games for serious purposes.

Results

The development of Serious Games in the history of humankind is shown in a timeline. Games with a serious intention have been part of the culture since the beginning of humanity. Serious Games is not a new technology trigger, but has always been closely linked to learning. Various factors influencing the development of Serious Games have led to a very diverse, interprofessional and interdisciplinary field of research and application.

Conclusions

Serious Games (for Health) and playful applications like gamification offer great potential for work in prevention, health promotion, medicine and health education. Due to the widespread use of the medium of play as an integral aspect of everyday life and culture, the achievement of hard-to-reach groups through this type of medium is very well possible. Aspects such as immersion, flow, storytelling and high interactivity and direct feedback make games an effective intervention strategy.

     

Prospective evaluation of intra-observer variability of the hydronephrosis index in sonographic examination of 44 patients with acute renal colic

Purpose

The aim of our prospective designed study was to confirm the intra-observer agreement of assessments of the hydronephrosis index (HI) with a sonographic technique that potentially provides additional information in patients with acute renal colic (ARC).

Methods

Sonographic measurement of HI and valuation of common clinical criteria were performed in 44 consecutive patients presenting with unilateral stone-related ARC. HI of colic side was recorded twice in predefined time intervals. Intra-observer agreement was evaluated with the Spearman’s rank correlation/rho (ρ) for attributive-metric characteristics. Data of HI-measurement on the colic side were compared with data of the unaffected side using t test.

Results

Intra-observer agreement was significant for HI in the colic side (ρ = 0.918, p < 0.001) and in the unaffected side (ρ = 0.826, p < 0.001). The mean HI between colic and unaffected side differed significantly on the first evaluation (85.2 vs. 93.7, respectively; p < 0.001) and on the second evaluation (85.1 vs. 93.6, respectively; p < 0.001) as well.

Conclusions

The HI method is a slightly feasible examination method in patients presenting with stone-related renal colic. Moreover, it offers a solid discrimination between obstruction and non-obstruction. Our prospective trial illustrates HI as a reproducible method with a high-grade intra-observer agreement. However, potential change of values under medical expulsive therapy and coherency with the functionality of the obstructed kidney may lead to bias and therefore remain to be analyzed. Further studies to specify exact thresholds for this method and to state our findings are required.     

Streptococcus mitis Strains Causing Severe Clinical Disease in Cancer Patients

The genetically diverse viridans group streptococci (VGS) are increasingly recognized as the cause of a variety of human diseases. We used a recently developed multilocus sequence analysis scheme to define the species of 118 unique VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68 patients) and S. oralis (22 patients) were the most frequently identified strains. Compared with patients infected with non–S. mitis strains, patients infected with S. mitis strains were more likely to have moderate or severe clinical disease (e.g., VGS shock syndrome). Combined with the sequence data, whole-genome analyses showed that S. mitis strains may more precisely be considered as >2 species. Furthermore, we found that multiple S. mitis strains induced disease in neutropenic mice in a dose-dependent fashion. Our data define the prominent clinical effect of the group of organisms currently classified as S. mitis and lay the groundwork for increased understanding of this understudied pathogen.     

The PML domain of PML–RARα blocks senescence to promote leukemia

In most acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein–retinoic acid receptor α (PML–RARα) fusion gene. Although expression of the human PML fusion in mice promotes leukemia, its efficiency is rather low. Unexpectedly, we find that simply replacing the human PML fusion with its mouse counterpart results in a murine PML–RARα (mPR) hybrid protein that is transformed into a significantly more leukemogenic oncoprotein. Using this more potent isoform, we show that mPR promotes immortalization by preventing cellular senescence, impeding up-regulation of both the p21 and p19^ARF cell-cycle regulators. This induction coincides with a loss of the cancer-associated ATRX/Daxx–histone H3.3 predisposition complex and suggests inhibition of senescence as a targetable mechanism in APL therapy.Acute promyelocytic leukemia (APL) is characterized by chromosomal translocations involving retinoic acid receptor alpha (RARα) with a limited number of translocation partners. A common feature of APL-promoting fusion proteins is their ability to self-associate. Indeed, previous studies have shown that fusion of RARα with self-associating domains is sufficient to render RARα leukemogenic (1). In APL patients, the predominant leukemogenic protein found in 95–99% of cases is the result of the fusion of promyelocytic leukemia protein (PML) with RARα (human PML–RARα; hPR) (2, 3). RARα and PML are regulatory proteins implicated in multiple aspects of differentiation and development (4) and apoptosis and cellular senescence (5, 6), respectively. Despite speculation, the relevance of senescence in APL is not fully understood (7, 8).Current mouse models recapitulate many key features of the human disease, including a malignant promyelocytic phenotype and sensitivity to all-trans retinoic acid (ATRA), but suffer from incomplete penetrance and long latency until disease presentation (1, 9, 10). We reasoned that the relatively low leukemogenic activity of hPR in mice might be due to modest sequence identity between human and mouse PML (PML: 63% identity; RARα: 98% identity). Consistent with this notion, we have designed an “experimental oncoprotein” corresponding to the fusion of mouse PML with RARα (mPR), which produced myelocytic leukemia similar to hPR-induced murine APL (10) but with higher penetrance and shorter latency periods. Notably, expression of mPR disrupted PML nuclear bodies (PML-NBs), phenocopying hPR-induced APL (11, 12). We show here that senescence-related up-regulation of p21 and p19 is completely lost in primary murine bone marrow cells upon expression of mPR. Furthermore, we find that the assembly of the death domain associated protein (Daxx)–alpha thalassemia/mental retardation syndrome X-linked (ATRX) complex at PML-NBs is disrupted by mPR expression, implicating this PML–ATRX–Daxx (PAX) complex in cellular senescence and tumor suppressor activity for PML (13). This study provides experimental evidence for the relevance of PML-NB disruption in APL genesis.