Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer

Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. But it is unclear whether microRNAs play a role in regulating oncogene expression in fulvestrant-treated prostate cancer. Here, this study reports hsa-miR-765 as the first fulvestrant-driven, ERβ-regulated miRNA exhibiting significant tumor suppressor activities like fulvestrant, against prostate cancer cell growth via blockage of cell-cycle progression at the G2/M transition, and cell migration and invasion possibly via reduction of filopodia/intense stress-fiber formation. Fulvestrant was shown to upregulate hsa-miR-765 expression through recruitment of ERβ to the 5′-regulatory-region of hsa-miR-765. HMGA1, an oncogenic protein in prostate cancer, was identified as a downstream target of hsa-miR-765 and fulvestrant in cell-based experiments and a clinical study. Both the antiestrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression. In a neo-adjuvant study, levels of hsa-miR-765 were increased and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose (250 mg) of fulvestrant 28 days before prostatectomy. These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer. © 2014 Leung et al

Barriers to and facilitators of successful implementation of a palliative approach to care in primary care practices: a mixed methods study

Objective Integrating a palliative approach to care into primary care is an emerging evidence-based practice. Despite the evidence, this type of care has not been widely adopted into primary care settings. The objective of this study was to examine the barriers to and facilitators of successful implementation of a palliative approach to care in primary care practices by applying an implementation science framework.Design This convergent mixed methods study analysed semistructured interviews and expression of interest forms to evaluate the implementation of a protocol, linked to implementation strategies, for a palliative approach to care called Early Palliation through Integrated Care (EPIC) in three primary care practices. This study assessed barriers to and facilitators of implementation of EPIC and was guided by the Consolidated Framework for Implementation Research (CFIR). A framework analysis approach was used during the study to determine the applicability of CFIR constructs and domains.Setting Primary care practices in Canada. Interviews were conducted between September 2020 and November 2021.Participants 10 individuals were interviewed, who were involved in implementing EPIC. Three individuals from each practice were reinterviewed to clarify emerging themes.Results Overall, there were implementation barriers at multiple levels that caused some practices to struggle. However, barriers were mitigated when practices had the following facilitators: (1) a high level of intra-practice collaboration, (2) established practices with organisational structures that enhanced communications, (3) effective leveraging of EPIC project supports to transition care, (4) perceptions that EPIC was an opportunity to make a long-term change in their approach to care as opposed to a limited term project and (5) strong practice champions.Conclusions Future implementation work should consider assessing facilitators identified in our results to better gauge primary care pre-implementation readiness. In addition, providing primary care practices with support to help offset the additional work of implementing innovations and networking opportunities where they can share strategies may improve implementation success

A Behavioral analysis of nurses’ and pharmacists’ role in addressing vaccine hesitancy: scoping review

The purpose of this review was to identify, characterize, and map the existing knowledge on a) nurses’ and pharmacists’ perceived barriers and enablers to addressing vaccine hesitancy among patients; and b) strategies or interventions for nurses and pharmacists to address vaccine hesitancy in their practice. Our comprehensive search strategy targeted peer-reviewed and grey literature. Two independent reviewers screened papers and extracted data. We coded narrative descriptions of barriers and enablers and interventions using the Behavior Change Wheel. Sixty-six records were included in our review. Reported barriers (n = 9) and facilitators (n = 6) were identified in the capability, opportunity and motivation components. The majority of the reported interventions were categorized as education (n = 47) and training (n = 26). This current scoping review offers a detailed behavioral analysis of known barriers and enablers for nurses and pharmacists to address vaccine hesitancy and interventions mapped onto these behavioral determinants

Knowledge translation strategies used for sustainability of an evidence-based intervention in child health: a multimethod qualitative study

Abstract Background Sustainability of evidence-based interventions (EBIs) is suboptimal in healthcare. Evidence on how knowledge translation (KT) strategies are used for the sustainability of EBIs in practice is lacking. This study examined what and how KT strategies were used to facilitate the sustainability of Alberta Family Integrated Care (FICare)™, a psychoeducational model of care scaled and spread across 14 neonatal intensive care units, in Alberta, Canada. Methods First, we conducted an environmental scan of relevant documents to determine the use of KT strategies to support the sustainability of Alberta FICare™. Second, we conducted semi-structured interviews with decision makers and operational leaders to explore what and how KT strategies were used for the sustainability of Alberta FICare™, as well as barriers and facilitators to using the KT strategies for sustainability. We used the Expert Recommendations for Implementation Change (ERIC) taxonomy to code the strategies. Lastly, we facilitated consultation meetings with the Alberta FICare™ leads to share and gain insights and clarification on our findings. Results We identified nine KT strategies to facilitate the sustainability of Alberta FICare™: Conduct ongoing training; Identify and prepare local champions; Research co-production; Remind clinicians; Audit and provide feedback; Change record systems; Promote adaptability; Access new funding; and Involve patients/consumers and family members. A significant barrier to the sustainability of Alberta FICare™ was a lack of clarity on who was responsible for the ongoing maintenance of the intervention. A key facilitator to sustainability of Alberta FICare was its alignment with the Maternal, Newborn, Child & Youth Strategic Clinical Network (MNCY SCN) priorities. Co-production between researchers and health system partners in the design, implementation, and scale and spread of Alberta FICare™ was critical to sustainability. Conclusion This research highlights the importance of clearly articulating who is responsible for continued championing for the sustainability of EBIs. Additionally, our research demonstrates that the adaptation of interventions must be considered from the onset of implementation so interventions can be tailored to align with contextual barriers for sustainability. Clear guidance is needed to continually support researchers and health system leaders in co-producing strategies that facilitate the long-term sustainability of effective EBIs in practice

Ecophysiology of “Halarsenatibacter silvermanii” Strain SLAS-1T, gen. nov., sp. nov., a Facultative Chemoautotrophic Arsenate Respirer from Salt-Saturated Searles Lake, California ▿ †

Searles Lake occupies a closed basin harboring salt-saturated, alkaline brines that have exceptionally high concentrations of arsenic oxyanions. Strain SLAS-1T was previously isolated from Searles Lake (R. S. Oremland, T. R. Kulp, J. Switzer Blum, S. E. Hoeft, S. Baesman, L. G. Miller, and J. F. Stolz, Science 308:1305-1308, 2005). We now describe this extremophile with regard to its substrate affinities, its unusual mode of motility, sequenced arrABD gene cluster, cell envelope lipids, and its phylogenetic alignment within the order Halanaerobacteriales, assigning it the name “Halarsenatibacter silvermanii” strain SLAS-1T. We also report on the substrate dynamics of an anaerobic enrichment culture obtained from Searles Lake that grows under conditions of salt saturation and whose members include a novel sulfate reducer of the order Desulfovibriales, the archaeon Halorhabdus utahensis, as well as a close homolog of strain SLAS-1T

The Impact of Exercise on Cardiotoxicity in Pediatric and Adolescent Cancer Survivors: A Scoping Review

Childhood and adolescent cancer survivors are disproportionately more likely to develop cardiovascular diseases from the late effects of cardiotoxic therapies (e.g., anthracycline-based chemotherapy and chest-directed radiotherapy). Currently, dexrazoxane is the only approved drug for preventing cancer treatment-related cardiac damage. While animal models highlight the beneficial effects of exercise cancer treatment-related cardiac dysfunction, few clinical studies have been conducted. Thus, the objective of this scoping review was to explore the designs and impact of exercise-based interventions for managing cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors. Reviewers used Joanna Briggs Institute’s methodology to identify relevant literature. Then, 4616 studies were screened, and three reviewers extracted relevant data from six reports. Reviewers found that exercise interventions to prevent cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors vary regarding frequency, intensity, time, and type of exercise intervention. Further, the review suggests that exercise promotes positive effects on managing cancer treatment-related cardiac dysfunction across numerous indices of heart health. However, the few clinical studies employing exercise interventions for childhood and adolescent cancer survivors highlight the necessity for more research in this area

Trainee-led research using an integrated knowledge translation or other research partnership approaches: a scoping reviews

Abstract Background There are increasing expectations for researchers and knowledge users in the health system to use a research partnership approach, such as integrated knowledge translation, to increase the relevance and use of research findings in health practice, programmes and policies. However, little is known about how health research trainees engage in research partnership approaches such as IKT. In response, the purpose of this scoping review was to map and characterize the evidence related to using an IKT or other research partnership approach from the perspective of health research trainees in thesis and/or postdoctoral work. Methods We conducted this scoping review following the Joanna Briggs Institute methodology and Arksey and O’Malley’s framework. We searched the following databases in June 2020: MEDLINE, Embase, CINAHL and PsycINFO. We also searched sources of unpublished studies and grey literature. We reported our findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Results We included 74 records that described trainees’ experiences using an IKT or other research partnership approach to health research. The majority of studies involved collaboration with knowledge users in the research question development, recruitment and data collection stages of the research process. Intersecting barriers to IKT or other research partnerships at the individual, interpersonal and organizational levels were reported, including lack of skills in partnership research, competing priorities and trainees’ “outsider” status. We also identified studies that evaluated their IKT approach and reported impacts on partnership formation, such as valuing different perspectives, and enhanced relevance of research. Conclusion Our review provides insights for trainees interested in IKT or other research partnership approaches and offers guidance on how to apply an IKT approach to their research. The review findings can serve as a basis for future reviews and primary research focused on IKT principles, strategies and evaluation. The findings can also inform IKT training efforts such as guideline development and academic programme development