61 research outputs found

    Scaffold attachment factor B1 (SAFB1) heterozygosity does not influence Wnt-1 or DMBA-induced tumorigenesis

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    <p>Abstract</p> <p>Background</p> <p>Scaffold Attachment Factor B1 (SAFB1) is a multifunctional protein which has been implicated in breast cancer previously. We recently generated SAFB1 knockout mice (SAFB1<sup>-/-</sup>), but pleiotropic phenotypes including high lethality, dwarfism associated with low IGF-I levels, and infertility and subfertility in male and female mice, respectively, do not allow for straightforward tumorigenesis studies in these mice. Therefore, we asked whether SAFB1 heterozygosity would influence tumor development and progression in MMTV-Wnt-1 oncomice or DMBA induced tumorigenicity, in a manner consistent with haploinsufficiency of the remaining allele.</p> <p>Methods</p> <p>We crossed female SAFB1<sup>+/- </sup>(C57B6/129) mice with male MMTV-Wnt-1 (C57B6/SJL) mice to obtain SAFB1<sup>+/+</sup>/Wnt-1, SAFB1<sup>+/-</sup>/Wnt-1, and SAFB1<sup>+/- </sup>mice. For the chemical induced tumorigenesis study we treated 8 weeks old SAFB1<sup>+/- </sup>and SAFB<sup>+/+ </sup>BALB/c mice with 1 mg DMBA once per week for 6 weeks. Animals were monitored for tumor incidence and tumor growth. Tumors were characterized by performing H&E, and by staining for markers of proliferation and apoptosis.</p> <p>Results</p> <p>We did not detect significant differences in tumor incidence and growth between SAFB1<sup>+/+</sup>/Wnt-1 and SAFB1<sup>+/-</sup>/Wnt-1 mice, and between DMBA-treated SAFB1<sup>+/+ </sup>and SAFB1<sup>+/-</sup>mice. Histological evaluation of tumors showed that SAFB1 heterozygosity did not lead to changes in proliferation or apoptosis. There were, however, significant differences in the distribution of tumor histologies with an increase in papillary and cribriform tumors, and a decrease in squamous tumors in the SAFB1<sup>+/-</sup>/Wnt-1 compared to the SAFB1<sup>+/+</sup>/Wnt-1 tumors. Of note, DMBA treatment resulted in shortened survival of SAFB1<sup>+/- </sup>mice compared to their wildtype littermates, however this trend did not reach statistical significance.</p> <p>Conclusion</p> <p>Our data show that SAFB1 heterozygosity does not influence Wnt-1 or DMBA-induced mammary tumorigenesis.</p

    Integration of robotic surgery into routine practice and impacts on communication, collaboration, and decision making: A realist process evaluation protocol

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    Background: Robotic surgery offers many potential benefits for patients. While an increasing number of healthcare providers are purchasing surgical robots, there are reports that the technology is failing to be introduced into routine practice. Additionally, in robotic surgery, the surgeon is physically separated from the patient and the rest of the team, with the potential to negatively impact teamwork in the operating theatre. The aim of this study is to ascertain: how and under what circumstances robotic surgery is effectively introduced into routine practice; and how and under what circumstances robotic surgery impacts teamwork, communication and decision making, and subsequent patient outcomes. Methods and design: We will undertake a process evaluation alongside a randomised controlled trial comparing laparoscopic and robotic surgery for the curative treatment of rectal cancer. Realist evaluation provides an overall framework for the study. The study will be in three phases. In Phase I, grey literature will be reviewed to identify stakeholders' theories concerning how robotic surgery becomes embedded into surgical practice and its impacts. These theories will be refined and added to through interviews conducted across English hospitals that are using robotic surgery for rectal cancer resection with staff at different levels of the organisation, along with a review of documentation associated with the introduction of robotic surgery. In Phase II, a multi-site case study will be conducted across four English hospitals to test and refine the candidate theories. Data will be collected using multiple methods: the structured observation tool OTAS (Observational Teamwork Assessment for Surgery); video recordings of operations; ethnographic observation; and interviews. In Phase III, interviews will be conducted at the four case sites with staff representing a range of surgical disciplines, to assess the extent to which the results of Phase II are generalisable and to refine the resulting theories to reflect the experience of a broader range of surgical disciplines. The study will provide (i) guidance to healthcare organisations on factors likely to facilitate successful implementation and integration of robotic surgery, and (ii) guidance on how to ensure effective communication and teamwork when undertaking robotic surgery

    Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice

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    and why disruption of circadian rhythm may lead to tumorigenesis. oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor

    Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

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    To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Validation of maternal and terminal sheep breeding objectives using Irish field data

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    peer-reviewedGenetic evaluations provide producers with a tool to aid in breeding decisions and highlight the increase in performance achievable at the farm level through genetic gain. Despite this, large-scale validation of sheep breeding objectives using field data is lacking in the scientific literature. The objective of the present study was to evaluate the phenotypic differences for a range of economically important traits for animals divergent in genetic merit for the Irish national maternal and terminal sheep breeding objectives. A dataset of 17,356 crossbred ewes and 54,322 progeny differing in their maternal and terminal breeding index recorded in 139 commercial flocks was available. The association of the maternal index of the ewe or terminal index of the ram and a range of phenotypic performance traits, including lambing, lamb performance, ewe performance, and health traits, were undertaken. Ewes excelling on the maternal index had higher litter sizes and produced progeny with greater perinatal lamb survival, heavier live weights from birth to postweaning and reduced days to slaughter (P  0.05). Results from this study highlight that selecting either ewes or rams of superior maternal or terminal attributes will result in an improvement on pertinent performance traits of the national sheep flock, resulting in greater flock productivity and profitability.Irish Department of Agricultur
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