Sub-chronic toxicity study in rats orally exposed to nanostructured silica

Synthetic Amorphous Silica (SAS) is commonly used in food and drugs. Recently, a consumer intake of silica from food was estimated at 9.4 mg/kg bw/day, of which 1.8 mg/kg bw/day was estimated to be in the nano-size range. Food products containing SAS have been shown to contain silica in the nanometer size range (i.e. 5 – 200 nm) up to 43% of the total silica content. Concerns have been raised about the possible adverse effects of chronic exposure to nanostructured silica

Early gene expression changes during embryonic stem cell differentiation into cardiomyocytes and their modulation by monobutyl phthalate.

The Embryonic Stem cell Test (EST) is an in vitro alternative test designed for the prediction of embryotoxicity. The endpoint of the test is the interference with mesoderm-derived cardiac muscle differentiation observed under the microscope as beating muscle foci. The relative subjectivity of this endpoint, as well as the applicability domain and related predictivity need further to be defined to facilitate implementation of the EST into regulatory strategies. The use of transcriptomics techniques to monitor differentiation-related gene expression changes in the EST might improve the EST in each of these aspects. Therefore, we studied the gene expression profile in embryonic stem cells (ESC) in the early phase of differentiation and its modulation by exposure to the well known embryotoxicant monobutyl phthalate (MBP). Cells were exposed from the early embryoid body stage onwards and RNA was collected after 6, 12 and 24h of exposure. Samples were hybridized to spotted microarrays, containing 21,997-mer oligonucleotides. Differential gene expression patterns were analyzed. A total number of 43 genes that were found to be upregulated in this study as a consequence of induction of cardiomyocyte differentiation were combined in a gene set, named 'VAN_DARTEL_HEARTDIFF_24H'. Gene Set Enrichment Analysis (GSEA) comparative analysis using multiple gene set collections clearly showed that temporal changes in gene expression were functionally related to cardiomyocyte differentiation. Furthermore, exposure of embryoid bodies (EB) to MBP increased expression of pluripotency-, proliferation- and nonmesodermal differentiation-related gene sets, which indicates inhibition of mesodermal differentiation. The inhibition of mesoderm-derived cardiomyocyte differentiation by MBP exposure was most obvious through the downregulation of our novel gene set identified in this study, 'VAN_DARTEL_HEARTDIFF_24H', which specifically describes the niche of early cardiomyocyte differentiation. The gene set defined in this study might serve as a starting point for defining a dedicated gene set for early detection of embryotoxicity in the EST. Such a gene set may serve as an improved endpoint in the EST as compared to morphology, and will allow a more detailed definition of the applicability domain and predictivity of EST

Optical-field-ionization EUV lasing in a xenon cluster jet

The present work focused on the potential involvement of selective adaptations of the androgen receptor pathway in the initiation and progression of prostate cancer. We defined the androgen receptor pathway by selecting 200 genes that were androgen responsive in prostate cancer cell lines and/or xenografts. This androgen receptor pathway gene signature was then used for profiling prostate cancer xenografts and patient-derived samples. Approximately half of the androgen receptor pathway genes were up-regulated in well-differentiated prostate cancer compared with normal prostate. Functionally distinct parts of the androgen receptor pathway were specifically down-regulated in high-grade cancers. Unexpectedly, metastases have down-regulated the vast majority of androgen receptor pathway genes. The significance of this progressive down-regulation of androgen receptor pathway genes was shown for a few androgen receptor-regulated genes. Lower mRNA expression of HERPUD1, STK39, DHCR24, and SOCS2 in primary prostate tumors was correlated with a higher incidence of metastases after radical prostatectomy. HERPUD1 mRNA expression predicted the occurrence of metastases almost perfectly. In vitro experiments showed that overexpression of the stress response gene HERPUD1 rapidly induces apoptosis. Based on the functions of the genes within the distinct subsets, we propose the following model. Enhanced androgen receptor activity is involved in the early stages of prostate cancer. In well-differentiated prostate cancer, the androgen receptor activates growth-promoting as well as growth-inhibiting and cell differentiation genes resulting in a low growth rate. The progression from low-grade to high-grade prostate carcinoma and metastases is mediated by a selective down-regulation of the androgen receptor target genes that inhibit proliferation, induce differentiation, or mediate apoptosis

Improved Aortic Pulse Wave Velocity Assessment From Multislice Two-Directional In-Plane Velocity-Encoded Magnetic Resonance Imaging

Purpose: To evaluate the accuracy and reproducibility of aortic pulse wave velocity (PWV) assessment by in-plane velocity-encoded magnetic resonance imaging (MRI). Materials and Methods: In 14 patients selected for cardiac catheterization on suspicion of coronary artery disease and 15 healthy volunteers, PWV was assessed with multislice two-directional in-plane velocity-encoded MRI (PWVi.p.) and compared with conventionally assessed PWV from multisite one-directional through-plane velocity-encoded MRI (PWVt.p.). In patients, PWV was also obtained from intraarterially acquired pressure-time curves (PWVpressure), which is considered the gold standard reference method. In volunteers, PWVi.p. and PWVt.p. were obtained in duplicate in the same examination to test reproducibility. Results: In patients, PWVi.p. showed stronger correlation and similar variation with PWVpressure than PWVt.p.). (Pearson correlation r = 0.75 vs. r = 0.58, and coefficient of variation [COV] = 10% vs. COV = 12%, respectively). In volunteers, repeated PWVi.p. assessment showed stronger correlation and less variation than repeated PWVt.p. (proximal aorta: r = 0.97 and COV = 10% vs. r = 0.69 and COV = 17%; distal aorta: r = 0.94 and COV = 12% vs. r = 0.90 and COV = 16%; total aorta: r = 0.97 and COV = 7% vs. r = 0.90 and COV = 13%). Conclusion: PWVi.p. is an improvement over conventional PWVt.p. by showing higher agreement as compared to the gold standard (PWVpressure) and higher reproducibility for repeated MRI assessment.Vascular Biology and Interventio

Preventive home care of frail older people: a review of recent case management studies.

Preventive actions targeting community-dwelling frail older people will be increasingly important with the growing number of very old and thereby also frail older people. This study aimed to explore and summarize the empirical literature on recent studies of case/care management interventions for community-dwelling frail older people and especially with regard to the content of the interventions and the nurse's role and outcome of it. Very few of the interventions took either a preventive or a rehabilitative approach using psycho-educative interventions focusing, for instance, on self-care activities, risk prevention, health complaints management or how to preserve or strengthen social activities, community involvement and functional ability. Moreover, it was striking that very few included a family-oriented approach also including support and education for informal caregivers. Thus it seems that the content of case/care management needs to be expanded and more influenced by a salutogenic health care perspective. Targeting frail older people seemed to benefit from a standardized two-stage strategy for inclusion and for planning the interventions. A comprehensive geriatric assessment seemed useful as a base. Nurses, preferably trained in gerontological practice, have a key role in case/care management for frail older people. This approach calls for developing the content of case/care management so that it involves a more salutogenic, rehabilitative and family-oriented approach. To this end it may be useful for nurses to strengthen their psychosocial skills or develop close collaboration with social workers. The outcome measures examined in this study represented one of three perspectives: the consumer's perspective, the perspective of health care consumption or the recipient's health and functional ability. Perhaps effects would be expected in all three areas and thus these should be included in evaluative studies in addition to measures for family and/or informal caregiver's strain and satisfaction