Simulated Microgravity Regulates Gene Transcript Profiles of 2T3 Preosteoblasts: Comparison of the Random Positioning Machine and the Rotating Wall Vessel Bioreactor

Microgravity of spaceflight induces bone loss due in part to decreased bone formation by osteoblasts. We have previously examined the microgravity-induced changes in gene expression profiles in 2T3 preosteoblasts using the Random Positioning Machine (RPM) to simulate microgravity conditions. Here, we hypothesized that exposure of preosteoblasts to an independent microgravity simulator, the Rotating Wall Vessel (RWV), induces similar changes in differentiation and gene transcript profiles, resulting in a more confined list of gravi-sensitive genes that may play a role in bone formation. In comparison to static 1g controls, exposure of 2T3 cells to RWV for 3 days inhibited alkaline phosphatase activity, a marker of differentiation, and downregulated 61 genes and upregulated 45 genes by more than two-fold as shown by microarray analysis. The microarray results were confirmed with real time PCR for downregulated genes osteomodulin, bone morphogenic protein 4 (BMP4), runx2, and parathyroid hormone receptor 1. Western blot analysis validated the expression of three downregulated genes, BMP4, peroxiredoxin IV, and osteoglycin, and one upregulated gene peroxiredoxin I. Comparison of the microarrays from the RPM and the RWV studies identified 14 gravi-sensitive genes that changed in the same direction in both systems. Further comparison of our results to a published database showing gene transcript profiles of mechanically loaded mouse tibiae revealed 16 genes upregulated by the loading that were shown to be downregulated by RWV and RPM. These mechanosensitive genes identified by the comparative studies may provide novel insights into understanding the mechanisms regulating bone formation and potential targets of countermeasure against decreased bone formation both in astronauts and in general patients with musculoskeletal disorders

Managing Opportunities and Challenges of Co-Authorship

Research with the largest impact on practice and science is often conducted by teams with diverse substantive, clinical, and methodological expertise. Team and interdisciplinary research has created authorship groups with varied expertise and expectations. Co-authorship among team members presents many opportunities and challenges. Intentional planning, clear expectations, sensitivity to differing disciplinary perspectives, attention to power differentials, effective communication, timelines, attention to published guidelines, and documentation of progress will contribute to successful co-authorship. Both novice and seasoned authors will find the strategies identified by the Western Journal of Nursing Research Editorial Board useful for building positive co-authorship experiences

Comparison of the Population Excess Fraction of <i>Chlamydia trachomatis</i> Infection on Pelvic Inflammatory Disease at 12-months in the Presence and Absence of Chlamydia Testing and Treatment:Systematic Review and Retrospective Cohort Analysis

Background: The impact of Chlamydia trachomatis (chlamydia) control on the incidence of pelvic inflammatory disease (PID) is theoretically limited by the proportion of PID caused by chlamydia. We estimate the population excess fraction (PEF) of treated chlamydia infection on PID at 12-months in settings with widespread chlamydia control (testing and treatment) and compare this to the estimated PEF of untreated chlamydia. Methods: We used two large retrospective population-based cohorts of women of reproductive age from settings with widespread chlamydia control to calculate the PEF of treated chlamydia on PID at 12-months. We undertook a systematic review to identify further studies that reported the risk of PID in women who were tested for chlamydia (infected and uninfected). We used the same method to calculate the PEF in eligible studies then compared all estimates of PEF. Results: The systematic review identified a single study, a randomised control led trial of chlamydia screening (POPI-RCT). In the presence of testing and treatment <10% of PID at 12-months was attributable to treated (baseline) chlamydia infections (Manitoba: 8.86%(95%CI 7.15-10.75); Denmark: 3.84%(3.26-4.45); screened-arm POPI-RCT: 0.99%(0.00-29.06)). In the absence of active chlamydia treatment 26.44% (11.57-46.32) of PID at 12-months was attributable to untreated (baseline) chlamydia infections (deferred-arm POPI-RCT). The PEFs suggest that eradicating baseline chlamydia infections could prevent 484 cases of PID at 12-months per 100,000 women in the untreated setting and 13- 184 cases of PID per 100,000 tested women in the presence of testing and treatment. Conclusion: Testing and treating chlamydia reduced the PEF of chlamydia on PID by 65% compared to the untreated setting. But in the presence of testing and treatment over 90% of PID could not be attributed to a baseline chlamydia infection. More information is needed about the aetiology of PID to develop effective strategies for improving the reproductive health of women

CLIENTS AS TEACHERS: THE 7 QUALITIES MOST DESIRED IN A THERAPIST

Little previous research has directly asked clients to identify the qualities they most desire in a therapist. The current study took place over the summer of 2016 utilizing a questionnaire format that asked over 120 individuals receiving out-patient and residential clinical therapeutic services, to identify the top seven qualities they most desired in a therapist. Participants chose from a list of 33 client-generated adjectives derived from an original focus group of partial-hospitalization and intensive outpatient therapy clients. This study’s participants had the opportunity to also identify and add qualities that were not listed among the original 33 options provided. The study found that clients most valued qualities that can be developed through Mindfulness practices, shedding light on an under-emphasized, but potentially rich area of development in the conception of graduate psychology training curricula. The research outcomes identified domains that, from a client-centered perspective, enhance clients’ engagement in therapy, decrease and repair therapeutic ruptures, and advance the field’s understanding of how therapeutic interventions are most effectively delivered

Development and psychometric properties of a brief measure of subjective decision quality for breast cancer treatment

Abstract Background Breast cancer patients face several preference-sensitive treatment decisions. Feelings such as regret or having had inadequate information about these decisions can significantly alter patient perceptions of recovery and recurrence. Numerous objective measures of decision quality (e.g., knowledge assessments, values concordance measures) have been developed; there are far fewer measures of subjective decision quality and little consensus regarding how the construct should be assessed. The current study explores the psychometric properties of a new subjective quality decision measure for breast cancer treatment that could be used for other preference sensitive decisions. Methods 320 women aged 20–79 diagnosed with AJCC stage 0 – III breast cancer were surveyed at two cancer specialty centers. Decision quality was assessed with single items representing six dimensions: regret, satisfaction, and fit as well as perceived adequacy of information, time, and involvement. Women rated decision quality for their overall treatment experience and surgery, chemotherapy, and radiation decisions separately. Principle components was used to explore factor structure. After scales were formed, internal consistency was computed using Cronbach’s alpha. The association of each of the four final scales with patient characteristics scores was examined by Pearson correlation. Results For overall breast cancer treatment as well as surgery, chemotherapy, and radiation decisions, the six items yielded a single factor solution. Factor loadings of the six decision items were all above .45 across the overall and treatment-specific scales, with the exception of “Right for You” for chemotherapy and radiation. Internal consistency was 0.77, 0.85, 0.82, and 0.78 for the overall, surgery, chemotherapy, and radiation decision quality scales, respectively. Conclusions Our measure of subjective appraisal of breast cancer treatment decisions includes 5 related elements; regret and satisfaction as well as perceived adequacy of information, time, and involvement. Future research is needed to establish norms for the measure as is further psychometric testing, particularly to examine how it is associated with outcomes such as quality of life, psychological coping and objective decision quality.http://deepblue.lib.umich.edu/bitstream/2027.42/109727/1/12911_2014_Article_110.pd

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

STUDENT SERVICES IN DISTANT LEARNING ENVIRONMENTS

At the end of the millennium in which the idea of the university has blossomed, population growth is outpacing the world’s capacity to give people access to universities. A sizable new university would now be needed every week merely to sustain current participation rates in higher education....Sir John S. Daniel, Vice Chancellor of The Open University; 6; p. 1 Traditional higher education institutions will probably be successful in the distance learning market if these two services are carefully developed and maintained: 1. provide quality learning experiences for students. 2. provide quality STUDENT SUPPORT SERVICES

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al