51 research outputs found

    Discontinuation of rLH two days before hCG may increase the number of oocytes retrieved in IVF

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    <p>Abstract</p> <p>Background</p> <p>Administration of recombinant luteinizing hormone (rLH) in controlled ovarian hyperstimulation may benefit a subpopulation of patients. However, late follicular phase administration of high doses of rLH may also reduce the size of the follicular cohort and promote monofollicular development.</p> <p>Methods</p> <p>To determine if rLH in late follicular development had a negative impact on follicular growth and oocyte yield, IVF patients in our practice who received rFSH and rLH for the entire stimulation were retrospectively compared with those that had the rLH discontinued at least two days prior to hCG trigger.</p> <p>Results</p> <p>The two groups had similar baseline characteristics before stimulation with respect to age, FSH level and antral follicle count. However, the group which had the rLH discontinued at least two days prior to their hCG shot, had a significantly higher number of oocytes retrieved, including a higher number of MII oocytes and number of 2PN embryos.</p> <p>Conclusions</p> <p>When using rLH for controlled ovarian hyperstimulation, administering it from the start of stimulation and stopping it in the late follicular phase, at least two days prior to hCG trigger, may increase oocyte and embryo yield.</p

    BORIS expression in ovarian cancer precursor cells alters the CTCF cistrome and enhances invasiveness through GALNT14

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    High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy

    The Time to Act Is Now: Addressing the Challenges of Being a Student, Staff, or Faculty Member at DU While Also Being a Parent to Young Children

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    The growing number of undergraduate and graduate students who are simultaneously raising children while attending school requires the attention of institutions that want to support their students through the completion of their intended program. Compared to traditional students, these students have greater time and financial restraints, lower graduation rates, and require accommodation, support, and resources to help them maintain their academic standing. This issue is not isolated to just students however. Staff and faculty at academic institutions are also balancing their family and work responsibilities. With an increase in the number of households where one or two adults work full time, more institutional employees are having to negotiate issues of childcare, parental leave, and the ways in which their family responsibilities are perceived by colleagues and employers. In 2017, it was found that many DU community members were struggling with issues of childcare, a child friendly environment at work, and institutional policies related to childcare at the University. These findings led to a study, conducted by the Applied Anthropology class of 2018, aimed at identifying solutions and recommendations for the aforementioned challenges. The study was exploratory and utilized mixed qualitative data collection and analysis methods. The class conducted interviews, surveys, and archival research and used thematic analysis techniques to identify overarching themes that informed the findings and suggestions of this project. Through this research three major needs were identified: clear communication of policies, accommodations for students, and on-site day care. Respondents from this and previous studies at DU identified that classroom policies, policies regarding parental leave, available childcare, and Fisher were being communicated either ineffectively or inaccurately. This has led to confusion, frustration, feelings of job insecurity, and unmet expectations regarding what resources and support DU actually offers parents. There is also a lack of policies in place for student parents, which makes creating schedules and fulfilling academic requirements more challenging for these nontraditional students. The most significant issue identified however was the lack of childcare at DU and the desire for an on-site daycare center. Respondents explained that Denver has a limited number of available, convenient, and affordable daycare options, that Fisher is not meeting their needs, and that they would like to see a facility designed specifically for DU students, staff, and faculty. In response to these challenges, this study suggests the assemblage and dissemination of accurate and clearly communicated childcare related policies, the creation of policies for student parents, and an on-site daycare facility for the DU community. Research and efforts to understand and alleviate these challenges have occurred at DU since the 1970s, and many of the identified needs and desired solutions have not changed over the past fifty years. However, because previous efforts have been powered by those in need of services, the momentum behind each effort has inevitably dissolved. A way to accomplish and sustain these suggestions and actively work towards making DU a more child and family friendly campus is by creating a permanent employee position at DU to handle these issues. This would help centralize information and policies, assist with their clear communication, and focus consistent and sustainable efforts towards helping DU students, staff, and faculty balance their work and family life

    Family physician leadership during the COVID-19 pandemic: roles, functions and key supports.

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    PURPOSE: Strong leadership in primary care is necessary to coordinate an effective pandemic response; however, descriptions of leadership roles for family physicians are absent from previous pandemic plans. This study aims to describe the leadership roles and functions family physicians played during the COVID-19 pandemic in Canada and identify supports and barriers to formalizing these roles in future pandemic plans. DESIGN/METHODOLOGY/APPROACH: This study conducted semi-structured qualitative interviews with family physicians across four regions in Canada as part of a multiple case study. During the interviews, participants were asked about their roles during each pandemic stage and the facilitators and barriers they experienced. Interviews were transcribed and a thematic analysis approach was used to identify recurring themes. FINDINGS: Sixty-eight family physicians completed interviews. Three key functions of family physician leadership during the pandemic were identified: conveying knowledge, developing and adapting protocols for primary care practices and advocacy. Each function involved curating and synthesizing information, tailoring communications based on individual needs and building upon established relationships. PRACTICAL IMPLICATIONS: Findings demonstrate the need for future pandemic plans to incorporate formal family physician leadership appointments, as well as supports such as training, communication aides and compensation to allow family physicians to enact these key roles. ORIGINALITY/VALUE: The COVID-19 pandemic presents a unique opportunity to examine the leadership roles of family physicians, which have been largely overlooked in past pandemic plans. This study\u27s findings highlight the importance of these roles toward delivering an effective and coordinated pandemic response with uninterrupted and safe access to primary care

    Models for Access to Maternal Smoking cessation Support (MAMSS): a study protocol of a quasi-experiment to increase the engagement of pregnant women who smoke in NHS Stop Smoking Services

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    Background: Maternal smoking is a key cause of poor outcomes for mothers, babies and children and Wales has higher rates of smoking in pregnancy than any other UK country. Despite various improvements within the NHS Stop Smoking Service to strengthen the intervention for pregnant women, referrals and successful quit attempts for this group have continued to remain extremely low. A key element of UK national guidance for smoking cessation during pregnancy is to provide a flexible and tailored service to help increase levels of engagement. This study aims to test the effectiveness of three different models of service delivery to address the gap in the evidence base about how to deliver a flexible, tailored smoking cessation service to pregnant women. Methods: This study will adopt a quasi-experimental design over a 12 month period. The setting is four of Wales’ seven Health Boards using an integrated approach between maternity services, local public health teams and the NHS Stop Smoking Service. Core recommendations from UK public health guidance are being implemented across intervention and usual care sites. Stop smoking support for pregnant women in intervention sites is being delivered more flexibly than in usual care sites. Both qualitative and quantitative approaches will be adopted to capture important contextual information and consider multiple perspectives. A health economic analysis will be undertaken using a cost-consequences analysis approach. The primary outcome measure is engagement with stop smoking services (defined as having at least one face-to-face therapeutic contact with a clinician). Discussion: Supporting pregnant women to stop smoking is a challenging area of public health. The proposed study will address several areas where there are key evidence gaps relating to smoking cessation interventions for pregnant women. Specifically, how best to encourage pregnant women to attend a specialist stop smoking support service, how to deliver the service and who should provide it

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Analysis of Centruroides (Scorpion) Immune F(ab’)2 (Equine) administration by slow intravenous push

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    AbstractScorpion envenomation is a common emergency department presentation in Arizona and antivenom is often administered . This study evaluates the safety of Centruroides (Scorpion) Immune F(ab’)2 (Equine) administered as a single-vial-serial dosing strategy via slow intravenous push (IVP) over five minutes in the emergency department. This was a retrospective chart review of patients who received at least one vial of antivenom between April 1, 2019, and July 31, 2021. The primary outcome of this study was the rate of the serious antivenom administration-related adverse events. Twenty-five patients were included. One patient met criteria for a serious administration-related adverse event. No other serious administration, non-serious administration, or non-administration related adverse events were found. Neither grade of envenomation, repeat doses, nor total number of vials affected the rate of serious, non-serious, or non-administration-related adverse events. The primary outcome of a serious administration-related adverse event occurred in one patient (4%) with a grade IV envenomation

    The Effects of Biophilic Art on Affective Well-Being

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    Current research indicates the positive benefits of biophilia as well as art on affective well-being. However, there is a knowledge gap surrounding the effects of biophilic art on affective well-being, specifically when integrated into design. This study examines the effects of biophilic art compared to actual biophilia on affective well-being in the context of biophilic design elements. We hypothesise that actual biophilia and biophilic art have similar effects on affective well-being. We conducted an independent-samples T-test between the two conditions on 10 measures: Motivated, Calm, Tired, Bored, Gloomy, Active, At ease, Anxious, Annoyed, and Happy. Our preliminary findings reveal there is no significant difference found between the two conditions on any measure, indicating that biophilic art may be an appropriate substitute for actual biophilia in interior design. Disclaimer: “UBC SEEDS provides students with the opportunity to share the findings of their studies, as well as their opinions, conclusions and recommendations with the UBC community. The reader should bear in mind that this is a student project/report and is not an official document of UBC. Furthermore readers should bear in mind that these reports may not reflect the current status of activities at UBC. We urge you to contact the research persons mentioned in a report or the SEEDS Coordinator about the current status of the subject matter of a project/report.”Arts, Faculty ofPsychology, Department ofUnreviewedUndergraduat
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