Expression of decitabine-targeted oncogenes in meningiomas in vivo

Neurosurgical Review - Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine...     

Psychodramatiker*innen und ihr sehr persönlicher Umgang mit ihrem Handwerkszeug

Zeitschrift für Psychodrama und Soziometrie - In diesem Artikel der Zeitschrift für Psychodrama und Soziometrie geben fünf Psychodramatiker*innen Einblick in ihren Praxisalltag und...     

Temporal delimitation of the healing phases via monitoring of fracture callus stiffness in rats

The healing process consists of at least three phases: inflammatory, repair, and remodeling phase. Because callus stiffness correlates with the healing phases, it is suitable for evaluating the fracture healing process. Our aim was to develop a method which allows determination of callus stiffness in vivo, the healing time and the duration of the repair phase. The right femurs of 16 Wistar rats were osteotomized and stabilized with either more rigid or more flexible external fixation. Fixator deformation was measured using strain gauges during gait analysis. The strains were recalculated as the callus stiffness over the time course of healing, and the healing phases were identified based on stiffness thresholds. Our hypothesis was that stabilization with more flexible external fixation prolongs the repair phase, therefore resulting in an extended healing time. Confirming our hypothesis, the duration of the repair phase (rigid: approximately 15 days, flexible: approximately 41 days) and the healing time (rigid: approximately 27 days, flexible: approximately 62 days) were significantly longer for more flexible external fixation. Our method allows the quantitative detection of differences in the healing time and duration of the repair phase without multiple time‐point sacrifices, which reduces the number of animals in experimental studies. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1589–1595, 2014.     

Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells

Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron‐committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2‐based reporter cell line that expressed eGFP under the control of a neuron‐specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2′‐O‐methyl substituted 2‐deoxy‐β‐D‐ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest‐derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neurodegenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity.     

Head impact exposure in youth football—Are current interventions hitting the target?

Restrictions on heading in youth football have been implemented in some countries to limit head impact exposure. However, current interventions remain poorly guided by evidence. Our objective was to quantify heading exposure in youth football, assessing the effects of sex and age. Football matches played during an international youth football tournament with no heading restrictions were directly observed, including players from both sexes (11-19 years). The elite senior level was included for comparison, using video analysis. All heading events were registered, classified, and assigned to individual players. Heading rates were calculated for each sex and age group. We observed a total of 267 matches, corresponding to 4011 player hours (1927 player hours for females, 2083 player hours for males). Males headed more frequently than females (2.7 vs 1.8 headers/player hour; P < .001). Heading rates increased with age (ANOVA, P < .001), approaching the elite senior level for players 16 years and older. There was substantial variation within teams for all age and sex groups, with the widest range (1-18 headers) observed for girls aged 19. Girls younger than 12 years had the lowest exposure, with an average of <2 players per team heading the ball, each with 1-2 headers. In conclusion, age and sex influence head impact exposure in youth football, and warrants careful consideration when introducing injury prevention measures. Males are more frequently exposed than females, heading rates increase with age, and there is substantial variation between players. Heading is a rare event in the youngest age groups, especially among females.