Movement behavior patterns composition remains stable, but individuals change their movement behavior pattern over time in people with a first-ever stroke

Background: Movement behaviors (i.e., physical activity levels, sedentary behavior) in people with stroke are not self-contained but cluster in patterns. Recent research identified three commonly distinct movement behavior patterns in people with stroke. However, it remains unknown if movement behavior patterns remain stable and if individuals change in movement behavior pattern over time. Objectives: 1) To investigate the stability of the composition of movement behavior patterns over time, and 2) determine if individuals change their movement behavior resulting in allocation to another movement behavior pattern within the first two years after discharge to home in people with a first-ever stroke. Methods: Accelerometer data of 200 people with stroke of the RISE-cohort study were analyzed. Ten movement behavior variables were compressed using Principal Componence Analysis and K-means clustering was used to identify movement behavior patterns at three weeks, six months, one year, and two years after home discharge. The stability of the components within movement behavior patterns was investigated. Frequencies of individuals’ movement behavior pattern and changes in movement behavior pattern allocation were objectified. Results: The composition of the movement behavior patterns at discharge did not change over time. At baseline, there were 22% sedentary exercisers (active/sedentary), 45% sedentary movers (inactive/sedentary) and 33% sedentary prolongers (inactive/highly sedentary). Thirty-five percent of the stroke survivors allocated to another movement behavior pattern within the first two years, of whom 63% deteriorated to a movement behavior pattern with higher health risks. After two years there were, 19% sedentary exercisers, 42% sedentary movers, and 39% sedentary prolongers. Conclusions: The composition of movement behavior patterns remains stable over time. However, individuals change their movement behavior. Significantly more people allocated to a movement behavior pattern with higher health risks. The increase of people allocated to sedentary movers and sedentary prolongers is of great concern. It underlines the importance of improving or maintaining healthy movement behavior to prevent future health risks after stroke

Astroculture – Figurations of Cosmology in Media and Arts

Astroculture is a testament to the literary imagination and theoretical innovation of the late Sonja A.J. Neef, who devised the term as an expanding horizon of collaborative research – into the powerful gravitational force exerted on culture by astronomical phenomena and imagery. It is also the name of a conference on the topic inspired by Neef and held at the Center for Advanced Studies Morphomata at the University of Cologne in November, 2011. Indeed, Astroculture is a perfect instance of a morphome, the overall target of the Cologne College’s ongoing symposia: a persistent trope or topos of cultural fascination and transcription appearing across a gamut of civilizations and historical periods. Commentary in this volume ranges from Claudius Ptolemy’s mapping of the universe and the emergence of a pluralistic cosmology in seventeenth-century Europe to the spread of planetariums, the Whole Earth Catalog, and the contemporary artwork of Ingo Günter. With interventions by David Aubin, Lucía Ayala, Monika Bernold, Dietrich Boschung, Bruce Clarke, Gerd Graßhoff, Hans-Christian von Hermann, Martina Leeker, Patricia Pisters, and Henry Sussman

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

BackgroundIn the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.MethodsFrom 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.FindingsWe found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.InterpretationWe showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT

Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher\u27s least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status

The MD Anderson prostate cancer patient-derived xenograft series (MDA PCa PDX) captures the molecular landscape of prostate cancer and facilitates marker-driven therapy development

BACKGROUND: Advances in prostate cancer (PCa) lag behind other tumor types partly due to the paucity of models reflecting key milestones in PCa progression. OBJECTIVE: To develop clinically relevant PCa models. DESIGN: Since 1996 we have generated clinically annotated patient-derived xenografts (PDXs) (the MDA PCa PDX series) linked to specific phenotypes reflecting all aspects of clinical PCa. RESULTS: We studied two cell line-derived xenografts and the first 80 PDXs derived from 47 human PCa donors. Of these, 47 PDXs derived from 22 donors are working models and can be expanded either as cell lines (MDA PCa 2a and 2b) or PDXs. The histopathologic, genomic, and molecular characteristics (AR, ERG, and PTEN loss) maintain fidelity with the human tumor and correlate with published findings. PDX growth response to mouse castration and targeted therapy illustrate their clinical utility. Comparative genomic hybridization and sequencing show significant differences in oncogenic pathways in pairs of PDXs derived from different areas of the same tumor. We also identified a recurrent focal deletion in an area that includes the SPOPL gene in PDXs derived from 7 human donors out of 28 studied (25%). SPOPL is a SPOP paralog, and SPOP mutations define a molecular subclass of PCa. SPOPL deletions are found in 7% of TCGA PCas, which suggests that our cohort is a reliable platform for targeted drug development. CONCLUSIONS: The MDA PCa PDX series is a dynamic resource that captures the molecular landscape of PCas progressing under novel treatments and enables optimization of PCa-specific, marker-driven therapy

Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series

PURPOSE: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer. EXPERIMENTAL DESIGN: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. RESULTS: The cohort recapitulates clinically reported alterations in prostate cancer genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped on the basis of morphologic classification. DNA damage response-associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine prostate cancer in a cross-interrogation of PDX/patient datasets. CONCLUSIONS: We addressed the gap in clinically relevant prostate cancer models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives