Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.

E-Learning 2.0 in hydraulic engineering education

In this contribution the experiences with e-Learning 2.0 applications by using a Wiki for the education in hydraulic engineering are shown. Up to now important information for the students has been prepared by the instructor. For this project the students were asked to collaborate and search on their own for the information they needed. Therefore a Wiki-system was used. For the engineering practice a self dependent realisation of tasks is an important requirement which students should be prepared for. With the help of online communication there should be shown the possibilities for students for working together in an interdisciplinary team. The positive experiences as well as the results of the evaluation of this project plead for a continuation of the application of e-Learning 2.0 for education. The comparison of results of tests without using Wiki and with using Wiki shows a qualitative tendency of better marks. In this contribution we present the application of Wiki in hydraulic engineering but the results can also be used for other engineering disciplines.

A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm.

BACKGROUND Most guidelines recommend at least 2-cm excision margin for melanomas thicker than 2 mm. OBJECTIVE We evaluated whether 1- or 2-cm excision margins for melanoma (>2 mm) result in different outcomes. METHODS This is a retrospective cohort study on patients with melanomas (>2 mm) who underwent tumor excision with 1-cm (228 patients) or 2-cm (97 patients) margins to investigate presence of local recurrences, locoregional and distant metastases, and disease-free and overall survival. RESULTS In all, 325 patients with mean age of 61.84 years and Breslow thickness of 4.36 mm were considered for the study with a median follow-up of 1852 days (1995-2012). There was no significant difference in the frequency of locoregional and distant metastasis between the 2 groups (P = .311 and .571). The survival analysis showed no differences for disease-free (P = .800; hazard ratio 0.948; 95% confidence interval 0.627-1.433) and overall (P = .951; hazard ratio 1.018; 95% confidence interval 0.575-1.803) survival. LIMITATIONS The study was not prospectively randomized. CONCLUSIONS Our study did not show any significant differences in important outcome parameters such as local or distant metastases and overall survival. A prospective study testing 1- versus 2-cm excision margin is warranted.

Ms.Ff.F.Stoltze 3. 627 - Brief von Marie Stoltze an Lyda Stoltze

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