Representativeness of personality and involvement preferences in a web-based survey on healthcare decision-making

Background: Obtaining a sample that is representative of the group of interest is of utmost importance in questionnaire studies. In a survey using a state authorized web-portal for citizen communication with authorities, we wanted to investigate the view of adult men on patient involvement in health care decision-making regarding Prostate-Specific Antigen test for prostatic cancer. In this paper, we report on sample characteristics and representativeness of our sample in terms of personality and baseline involvement preferences. Methods: We compared personality profiles (BFI-10) and baseline healthcare decision-making preferences (CPS) in our sample (n = 6756) to internationally available datasets. Pooled data from a) US, UK, Canada, Australia, and New Zealand (n = 1512), b) Germany, Netherlands, Switzerland, and Belgium (n = 1136), and c) Norway, Sweden, Finland, and Denmark (n = 1313) were used for BFI-10 comparisons. Regarding CPS, we compared our sample with three previous datasets relating to decision-making in cancer (n = 425, 387, and 199). Results: Although statistically significant differences particularly appeared in large dataset comparisons, sample BFI-10 and CPS profiles mostly were within the range of those previously reported. Similarity was greatest in BFI-10 comparisons with group a) where no statistically significant difference could be established in factors 'agreeableness' and 'neuroticism' (p = .095 and .578, respectively). Conclusion: Despite some variation, our sample displays personality and baseline preference profiles that are generally similar to those described in previous international studies. For example, this was the case with the BFI-10 'agreeableness' measure (incl. trust and fault-finding items), an important factor in healthcare decision-making

Elucidation of time-dependent systems biology cell response patterns with time course network enrichment

Advances in OMICS technologies emerged both massive expression data sets and huge networks modelling the molecular interplay of genes, RNAs, proteins and metabolites. Network enrichment methods combine these two data types to extract subnetwork responses from case/control setups. However, no methods exist to integrate time series data with networks, thus preventing the identification of time-dependent systems biology responses. We close this gap with Time Course Network Enrichment (TiCoNE). It combines a new kind of human-augmented clustering with a novel approach to network enrichment. It finds temporal expression prototypes that are mapped to a network and investigated for enriched prototype pairs interacting more often than expected by chance. Such patterns of temporal subnetwork co-enrichment can be compared between different conditions. With TiCoNE, we identified the first distinguishing temporal systems biology profiles in time series gene expression data of human lung cells after infection with Influenza and Rhino virus. TiCoNE is available online (https://ticone.compbio.sdu.dk) and as Cytoscape app in the Cytoscape App Store (http://apps.cytoscape.org/)

Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells

Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSC

Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells.

Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSC

Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility

Summary: Obesity is associated with increased risk for fragility fractures. However, the cellular mechanisms are unknown. Using a translational approach combining RNA sequencing and cellular analyses, we investigated bone marrow stromal stem cells (BM-MSCs) of 54 men divided into lean, overweight, and obese groups on the basis of BMI. Compared with BM-MSCs obtained from lean, obese BM-MSCs exhibited a shift of molecular phenotype toward committed adipocytic progenitors and increased expression of metabolic genes involved in glycolytic and oxidoreductase activity. Interestingly, compared with paired samples of peripheral adipose tissue-derived stromal cells (AT-MSCs), insulin signaling of obese BM-MSCs was enhanced and accompanied by increased abundance of insulin receptor positive (IR+) and leptin receptor positive (LEPR+) cells in BM-MSC cultures. Their hyper-activated metabolic state was accompanied by an accelerated senescence phenotype. Our data provide a plausible explanation for the bone fragility in obesity caused by enhanced insulin signaling leading to accelerated metabolic senescence of BM-MSCs. : Tencerova et al. show that in human obesity, BM-MSCs exhibit a hypermetabolic state defined by upregulation of insulin signaling with enhanced adipogenesis and increased intracellular reactive oxygen species (ROS), leading to a senescence bone microenvironment contributing to bone fragility. Moreover, increased abundance of IR+ and LEPR+ BM-MSCs is characteristic of this phenotype, with an activated metabolic rate in obese subjects. Keywords: obesity, skeletal fragility, bone marrow skeletal stem cells, adipose-derived stem cells, differentiation potential, adipogenesis, insulin signalin

Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor gamma

<p>Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of short-chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor gamma (PPAR gamma), as demonstrated using PPAR gamma antagonist, PPAR gamma knockdown, and transactivation assays, which show activation of PPAR gamma but not PPAR alpha and PPAR delta by SCFA. At concentrations required for PPAR gamma activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPAR gamma in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPAR gamma modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPAR gamma. Our data point to activation of PPARs as a novel mechanism of gene regulation by SCFA in the colon, in addition to other mechanisms of action of SCFA.</p>