FE-Simulation in der klinischen Osteoporoseforschung

Altersbedingte Osteoporose erhöht des Frakturrisiko. Übliche Diagnoseverfahren basieren auf DXA. Leider sind diese ungenau und erklären oft nicht die Effekte von Behandlungen. Eine neue Methode zur Bestimmung der Knochenfestigkeit beginnt derzeit, sich zu etablieren – die Finite-Elemente-Methode (FEM). Diese universelle, im Bereich der Technik weit verbreitete, Methode erlaubt es, die Diagnose und den Behandlungserfolg besser vorauszusagen als DXA. CT-basierende FE-Modelle sind stark von der Bildauflösung abhängig. In diesem Überblicksartikel werden drei unterschiedliche Modelltypen (μCT, HR-pQCT, QCT) vorgestellt und die Ergebnisse von densitometrischen und FE-Analysen verglichen. Dabei waren die FE-Ergebnisse den densitometrischen immer überlegen. Darüber hinaus erlaubt die FEM die Angabe eines biomechanischen Frakturrisikos. Dieser Vorteil der FE-Methode muss jedoch im Licht der höheren Röntgendosen und Betriebskosten der CT-Bildgebung betrachtet werden. Zukünftig wird die FE-Methode klinisch eine weite Verbreitung finden – die Frage ist nur wann und wie!

Temporal genetic structure and relatedness in the Tufted Duck Aythya fuligula suggests limited kin association in winter

Conspecific aggregation of waterfowl in winter is a common example of animal flocking behaviour, yet patterns of relatedness and temporal substructure in such social groups remain poorly understood even in common species. A previous study based on mark-recapture data showed that Tufted Ducks Aythya fuligula caught on the same day were re-caught together in subsequent winters more often than expected by chance, suggesting stable assortments of ‘socially familiar’ individuals between wintering periods. The genetic relationships within these social groups were not clear. Based on 191 individuals genotyped at 10 microsatellite markers, we investigated the temporal genetic structure and patterns of relatedness among wintering Tufted Ducks at Lake Sempach, Switzerland, in two consecutive winters. We found no evidence of genetic differentiation between temporal groups within or between winters. The average levels of relatedness in temporal groups were low and not higher than expected in random assortments of individuals. However, Mantel tests performed for each sex separately revealed significant negative correlations between the pairwise relatedness coefficients and the number of days between the capture dates of pairs of wintering Tufted Duck in males and females. This pattern suggests the presence of a small number of co-migrating same-sex sibling pairs in wintering flocks of Tufted Ducks. Our findings provide one of the first genetic analyses of a common duck species outside the breeding season and contribute to the understanding of social interactions in long-distance migratory birds.

The mini-clinical evaluation exercise during medical clerkships: are learning needs and learning goals aligned?

OBJECTIVES The generation of learning goals (LGs) that are aligned with learning needs (LNs) is one of the main purposes of formative workplace-based assessment. In this study, we aimed to analyse how often trainer–student pairs identified corresponding LNs in mini-clinical evaluation exercise (mini-CEX) encounters and to what degree these LNs aligned with recorded LGs, taking into account the social environment (e.g. clinic size) in which the mini-CEX was conducted. METHODS Retrospective analyses of adapted mini-CEX forms (trainers’ and students’ assessments) completed by all Year 4 medical students during clerkships were performed. Learning needs were defined by the lowest score(s) assigned to one or more of the mini-CEX domains. Learning goals were categorised qualitatively according to their correspondence with the six mini-CEX domains (e.g. history taking, professionalism). Following descriptive analyses of LNs and LGs, multi-level logistic regression models were used to predict LGs by identified LNs and social context variables. RESULTS A total of 512 trainers and 165 students conducted 1783 mini-CEXs (98% completion rate). Concordantly, trainer–student pairs most often identified LNs in the domains of ‘clinical reasoning’ (23% of 1167 complete forms), ‘organisation/efficiency’ (20%) and ‘physical examination’ (20%). At least one ‘defined’ LG was noted on 313 student forms (18% of 1710). Of the 446 LGs noted in total, the most frequently noted were ‘physical examination’ (49%) and ‘history taking’ (21%). Corresponding LNs as well as social context factors (e.g. clinic size) were found to be predictors of these LGs. CONCLUSIONS Although trainer–student pairs often agreed in the LNs they identified, many assessments did not result in aligned LGs. The sparseness of LGs, their dependency on social context and their partial non-alignment with students’ LNs raise questions about how the full potential of the mini-CEX as not only a ‘diagnostic’ but also an ‘educational’ tool can be exploited.

Independent polled mutations leading to complex gene expression differences in cattle

The molecular regulation of horn growth in ruminants is still poorly understood. To investigate this process, we collected 1019 hornless (polled) animals from different cattle breeds. High-density SNP genotyping confirmed the presence of two different polled associated haplotypes in Simmental and Holstein cattle co-localized on BTA 1. We refined the critical region of the Simmental polled mutation to 212 kb and identified an overlapping region of 932 kb containing the Holstein polled mutation. Subsequently, whole genome sequencing of polled Simmental and Holstein cows was used to determine polled associated genomic variants. By genotyping larger cohorts of animals with known horn status we found a single perfectly associated insertion/deletion variant in Simmental and other beef cattle confirming the recently published possible Celtic polled mutation. We identified a total of 182 sequence variants as candidate mutations for polledness in Holstein cattle, including an 80 kb genomic duplication and three SNPs reported before. For the first time we showed that hornless cattle with scurs are obligate heterozygous for one of the polled mutations. This is in contrast to published complex inheritance models for the bovine scurs phenotype. Studying differential expression of the annotated genes and loci within the mapped region on BTA 1 revealed a locus (LOC100848215), known in cow and buffalo only, which is higher expressed in fetal tissue of wildtype horn buds compared to tissue of polled fetuses. This implicates that the presence of this long noncoding RNA is a prerequisite for horn bud formation. In addition, both transcripts associated with polledness in goat and sheep (FOXL2 and RXFP2), show an overexpression in horn buds confirming their importance during horn development in cattle.

Postnatal Notch1 activation induces T‑cell malignancy in conditional and inducible mouse models

The Notch1 signaling pathway is essential for hematopoietic development. However, the effects of postnatal activation of Notch1 signaling on hematopoietic system is not yet fully understood. We previously generated ZEG‑IC‑Notch1 transgenic mice that have a floxed β‑geo/stop signal between a CMV promoter and intracellular domain of Notch1 (IC‑Notch1). Constitutively active IC‑Notch1 is silent until the introduction of Cre recombinase. In this study, endothelial/hematopoietic specific expression of IC‑Notch1 in double transgenic ZEG‑IC‑Notch1/Tie2‑Cre embryos induced embryonic lethality at E9.5 with defects in vascular system but not in hematopoietic system. Inducible IC‑Notch1 expression in adult mice was achieved by using tetracycline regulated Cre system. The ZEG‑IC‑Notch1/Tie2‑tTA/tet‑O‑Cre triple transgenic mice survived embryonic development when maintained on tetracycline. Post‑natal withdrawal of tetracycline induced expression of IC‑Notch1 transgene in hematopoietic cells of adult mice. The triple transgenic mice displayed extensive T‑cell infiltration in multiple organs and T‑cell malignancy of lymph nodes. In addition, the protein levels of p53 and alternative reading frame (ARF) were decreased in lymphoma‑like neoplasms from the triple transgenic mice while their mRNA expression remained unchanged, suggesting that IC‑Notch1 might repress ARF‑p53 pathway by a post‑transcriptional mechanism. This study demonstrated that activation of constitutive Notch1 signaling after embryonic development alters adult hematopoiesis and induces T‑cell malignancy.