Physical forces in myelination and repair: a question of balance?

A recent report in BMC Cell Biology examines how the balance of extracellular forces and intracellular contractions regulate the shape changes required for oligodendrocyte myelination. A failure of remyelination such as seen in multiple sclerosis could be caused by loss of this balance

Bestimmung des relativen Sprachinformationsgehalts in einzelnen Frequenzbändern und der Transferfunktion zur Vorhersage der Sprachverständlichkeit auf der Basis des Hörbarkeitsindex AI für das Sprachmaterial des Freiburger Sprachverständlichkeitstests

Für die Sprachverständlichkeitsberechnung anhand akustischer Faktoren mittels des Hörbarkeitsindex AI ist entscheidend für die Qualität der Vorhersage, dass für das jeweilige Sprachmaterial passende Wichtigkeits- und Transferfunktionen zugrundegelegt werden. Für den Freiburger Sprachverständlichkeitstest, einen in Deutschland sehr häufig verwendeten sprachaudiometrischen Einsilbertest, existieren bisher keine exakt zu diesem Sprachmaterial passenden Wichtigkeits- und Transferfunktionen. In dieser Studie wurde eine Wichtigkeits- sowie eine Transferfunktion für das Sprachmaterial des Freiburger Sprachverständlichkeitstests erstellt. Diese Funktionen können verwendet werden, um zunächst Werte des Hörbarkeitsindex AI und im Anschluss Werte der Sprachverständlichkeit für dieses Sprachmaterial zu berechnen. Die Funktionen wurden aus Messwerten der Sprachverständlichkeit von 68 normalhörenden Probanden unter verschiedenen Filter- und Maskierungsbedingungen mit sprechersimulierendem Rauschen erstellt. Die Wichtigkeitsfunktion zeigte sich eingipflig mit einem Maximum bei 1500-3000 Hz und einer Crossover Frequenz von 1451 Hz. Die Transferfunktion verläuft eher flach, wie es bei anderen Einsilbertests ebenfalls der Fall ist

Kartographierung des Digitalen in der Bildung: Über den Versuch des Abbildens, Ordnens und (Neu-)Denkens eines umfassenden Digitalisierungsbegriffs

Der Diskurs um Digitalisierung ist umfangreich und heterogen. Im Bildungskontext zeigt sich eine eher unreflektierte Begriffsverwendung, was etwa in der Rede von einer unmöglichen Digitalisierung von Bildung gipfelt. Zudem ist der Diskurs von einer westlich-industriellen Perspektive geprägt, die globale Fragen nach ökologischen, ökonomischen, anthropologischen und sozio-kulturellen Bedingungen der Entwicklung, Erzeugung, Nutzung und Entsorgung digitaler Medien außer Acht lässt. Kritisch gefragt: Denken wir etwa über Herstellungsbedingungen neuer Tablets oder die fachgerechte Entsorgung von Altgeräten nach? Wohl wissend, dass der Anspruch, die unterschiedlichen Aspekte der Digitalisierung im Bildungskontext zu kartographieren, vermessen ist, ein nicht abschließbares und damit notwendigerweise unvollständiges Unterfangen darstellt, wagen die Autoren eine Kartographierung einer umfassend gedachten Digitalisierung im Bildungskontext. Jede Kartographierung verringert durch Sammeln und (Neu-)Ordnen Unwissenheit. Ziel des Beitrags ist, die vielschichtigen Perspektiven auf den Diskurs um Digitalisierung freizulegen, die bisher eher verborgen und unthematisiert geblieben sind, um in einem umfassend gedachten Kontext zu verorten. Dabei entstehen unterschiedliche Versionen einer Kartographierung der Digitalisierung im Bildungskontext. (DIPF/Orig.

Patterns of local recurrence and dose fractionation of adjuvant radiation therapy in 462 patients with soft tissue sarcoma of extremity and trunk wall

Purpose To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.publishedVersio

Distinct multivariate structural brain profiles are related to variations in short- and long-delay memory consolidation across children and young adults

From early to middle childhood, brain regions that underlie memory consolidation undergo profound maturational changes. However, there is little empirical investigation that directly relates age-related differences in brain structural measures to memory consolidation processes. The present study examined memory consolidation of intentionally studied object-location associations after one night of sleep (short delay) and after two weeks (long delay) in normally developing 5-to-7-year-old children (n = 50) and young adults (n = 39). Behavioural differences in memory retention rate were related to structural brain measures. Our results showed that children, in comparison to young adults, retained correctly learnt object-location associations less robustly over short and long delay. Moreover, using partial least squares correlation method, a unique multivariate profile comprised of specific neocortical (prefrontal, parietal, and occipital), cerebellar, and hippocampal head and subfield structures in the body was found to be associated with variation in short-delay memory retention. A different multivariate profile comprised of a reduced set of brain structures, mainly consisting of neocortical (prefrontal, parietal, and occipital), hippocampal head, and selective hippocampal subfield structures (CA1-2 and subiculum) was associated with variation in long-delay memory retention. Taken together, the results suggest that multivariate structural pattern of unique sets of brain regions are related to variations in short-and long-delay memory consolidation across children and young adults

A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network

BACKGROUND: The nuclear receptors are a large family of eukaryotic transcription factors that constitute major pharmacological targets. They exert their combinatorial control through homotypic heterodimerisation. Elucidation of this dimerisation network is vital in order to understand the complex dynamics and potential cross-talk involved. RESULTS: Phylogeny, protein-protein interactions, protein-DNA interactions and gene expression data have been integrated to provide a comprehensive and up-to-date description of the topology and properties of the nuclear receptor interaction network in humans. We discriminate between DNA-binding and non-DNA-binding dimers, and provide a comprehensive interaction map, that identifies potential cross-talk between the various pathways of nuclear receptors. CONCLUSION: We infer that the topology of this network is hub-based, and much more connected than previously thought. The hub-based topology of the network and the wide tissue expression pattern of NRs create a highly competitive environment for the common heterodimerising partners. Furthermore, a significant number of negative feedback loops is present, with the hub protein SHP [NR0B2] playing a major role. We also compare the evolution, topology and properties of the nuclear receptor network with the hub-based dimerisation network of the bHLH transcription factors in order to identify both unique themes and ubiquitous properties in gene regulation. In terms of methodology, we conclude that such a comprehensive picture can only be assembled by semi-automated text-mining, manual curation and integration of data from various sources

Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analyzed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: -11.8 ± 4.3 ml min-1·1.73 m-2, p = 0.006). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex. Further randomized controlled studies are necessary to confirm this potential negative effect

Oral HPV Infection and Sexuality: A Cross-Sectional Study in Women

Human Papillomavirus (HPV) is the main risk factor for cervical cancers and is associated with close to 36% of oropharyngeal cancers. There is increasing evidence that oral HPV transmission is related to sexual behavior but to our knowledge studies that involve women who have sex with women have not been performed. We examined the prevalence of oral HPV according to sexual behavior among a population-based sample of 118 women and have made some inferences of possible predictors of oral HPV infection. Women were categorized as heterosexual (history of vaginal sex and/or oral sex with males only, n = 75), bisexual (history of vaginal sex and oral sex with females, n = 32) and other (no history of vaginal sex but oral sex with females [homosexuals], virgins and women with incomplete sexual exposure data, n = 11) The prevalence of oral HPV infection was 12/118 (10.2%) for the overall study population and was not significantly different between heterosexual and bisexual women (10.7% (8/75) vs. 12.5% (4/32), p = 0.784). There was no oral HPV detected among homosexual women, virgins or among women where sexual exposure was unknown. Never smokers were more likely to be oral HPV+ compared to former smokers (Adjusted Odds Ratio (Adj OR) = 0.1, 95% CI, 0.0–1.1) and there was no difference in risk between never smokers and current smokers (Adj OR = 0.7, 95% CI, 0.1–4.6). Twenty-five percent (3/12) of oral HPV+ women had a history of HPV and/or genital warts compared to 9% (10/106) of oral HPV-women (p = 0.104). For the women with a history of vaginal sex (n = 110), oral HPV status was statistically significantly different according to oral sex exposure (p = 0.039). A higher proportion of oral HPV-positive women reported that they had no history of oral sex exposure compared to oral HPV-negative women (4/12, 33% vs. 7/98, 8%). The prevalence of cervical HPV infection did not vary between heterosexuals and bisexuals (35.7% (25/70) vs. 35.5% (11/31), p-value 0.411) and for all other women the cervical HPV prevalence was significantly lower (11.1%, 1/9). Our study suggests that smoking and sexual behavior involving males rather than female partners may be possible predictors of oral HPV infection in women. Further studies with larger sample size are needed to confirm these findings