Purpose: To quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investigate associations with other adipose tissue (AT) compartments. The relationship between IMAT and insulin sensitivity was also examined.Materials and Methods: Standardized quantification of IMAT was performed in a large cohort (N = 249) at increased risk for type 2 diabetes in the right calf by T1‐weighted fast spin‐echo imaging at 1.5T (Magnetom Sonata; Siemens Healthcare). Additionally, whole‐body AT distribution was assessed. Insulin sensitivity was determined by glucose clamp.Results: Males showed significantly more IMAT than females (2.1 ± 1.1 cm² vs. 1.5 ± 0.9 cm²; P < 0.001). IMAT correlated well with other AT depots, especially with visceral AT (VAT; r_females = 0.52, P < 0.0001 vs. r_males = 0.42, P < 0.0001). Moreover, IMAT showed a negative correlation with the glucose infusion rate (GIR; r_females = −0.43, P = 0.0002 vs. r_males = −0.40, P = 0.0007).Conclusion: Quantification of IMAT is possible by standard MR techniques. AT distribution of the lower leg is comparable to the visceral compartment with males having higher IMAT/VAT but lower subcutaneous AT (SCAT). IMAT seems to be involved in the pathogenesis of insulin resistance, as shown by the significant negative correlation with GIR. J. Magn. Reson. Imaging 2009.

Introduction: Breast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well as chemoresistance. Consequently, great efforts have been made to understand the molecular mechanisms underlying cancer stem cell maintenance. In order to study these rare cells in-vitro, they are typically enriched via mammosphere culture. Here we developed a mammosphere-based negative selection shRNAi screening system suitable to analyse the involvement of thousands of genes in the survival of cells with cancer stem cell properties. Methods: We describe a sub-population expressing the stem-like marker CD44⁺/CD24^-/low in SUM149 that were enriched in mammospheres. To identify genes functionally involved in the maintenance of the sub-population with cancer stem cell properties, we targeted over 5000 genes by RNAi and tested their ability to grow as mammospheres. The identified candidate ATG4A was validated in mammosphere and soft agar colony formation assays. Further, we evaluated the influence of ATG4A expression on the sub-population expressing the stem-like marker CD44⁺/CD24^low. Next, the tumorigenic potential of SUM149 after up- or down-regulation of ATG4A was examined by xenograft experiments. Results: Using this method, Jak-STAT as well as cytokine signalling were identified to be involved in mammosphere formation. Furthermore, the autophagy regulator ATG4A was found to be essential for the maintenance of a sub-population with cancer stem cell properties and to regulate breast cancer cell tumourigenicity in vivo. Conclusion: In summary, we present a high-throughput screening system to identify genes involved in cancer stem cell maintenance and demonstrate its utility by means of ATG4A.

Parents caring for children with rare diseases fear the long-term progression of the child’s disease. The current study aims to systematically investigate the quality of life (QoL) in parents of children with different rare diseases. We performed a systematic literature search including quantitative studies on QoL of parents caring for children and adolescents with rare diseases in five databases (APA PsycArticles, APA PsycInfo, MEDLINE, PSYNDEXplus, and PubMed) published between 2000–2020. Of the 3985 titles identified, 31 studies met the inclusion criteria and were selected for narrative review. Studies were included if they investigated predictors of parental QoL or reported QoL compared to normative samples, parents of healthy children, or children with other chronic diseases. We used the Newcastle–Ottawa Scale to assess methodological quality. The systematic review revealed that parents of children with rare diseases experience reduced QoL compared to parents with healthy children and norm values. Psychosocial factors, beyond disease-specific predictors, were shown to influence parental QoL substantially and may thus present an essential aspect within interventions for this highly burdened group. Health care professionals should consider and address the impairment of parental QoL due to the child’s rare disease. We discuss insights into existing research gaps and improvements for subsequent work.