227 research outputs found

    Whole genome expression analysis within the angiotensin II-apolipoprotein E deficient mouse model of abdominal aortic aneurysm

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    Abstract\ud Background: An animal model commonly used to investigate pathways and potential therapeutic\ud interventions relevant to abdominal aortic aneurysm (AAA) involves subcutaneous infusion of\ud angiotensin II within the apolipoprotein E deficient mouse. The aim of this study was to investigate\ud genes differentially expressed in aneurysms forming within this mouse model in order to assess the\ud relevance of this model to human AAA.\ud Results: Using microarrays we identified genes relevant to aneurysm formation within\ud apolipoprotein E deficient mice. Firstly we investigated genes differentially expressed in the\ud aneurysm prone segment of the suprarenal aorta in these mice. Secondly we investigated genes that\ud were differentially expressed in the aortas of mice developing aneurysms relative to those that did\ud not develop aneurysms in response to angiotensin II infusion. Our findings suggest that a host of\ud inflammation and extracellular matrix remodelling pathways are upregulated within the aorta in\ud mice developing aneurysms. Kyoto Encyclopedia of Genes and Genome categories enriched in the\ud aortas of mice with aneurysms included cytokine-cytokine receptor interaction, leukocyte\ud transendothelial migration, natural killer cell mediated cytotoxicity and hematopoietic cell lineage.\ud Genes associated with extracellular matrix remodelling, such as a range of matrix\ud metalloproteinases were also differentially expressed in relation to aneurysm formation.\ud Conclusion: This study is the first report describing whole genome expression arrays in the\ud apolipoprotein E deficient mice in relation to aneurysm formation. The findings suggest that the\ud pathways believed to be critical in human AAA are also relevant to aneurysm formation in this\ud mouse model. The findings therefore support the value of this model to investigate interventions\ud and mechanisms of human AAA

    The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E

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    Schwann cell factor 1 (SC1), a p75 neurotrophin receptor–interacting protein, is a member of the positive regulatory/suppressor of variegation, enhancer of zeste, trithorax (PR/SET) domain-containing zinc finger protein family, and it has been shown to be regulated by serum and neurotrophins. SC1 shows a differential cytoplasmic and nuclear distribution, and its presence in the nucleus correlates strongly with the absence of bromodeoxyuridine (BrdU) in these nuclei. Here, we investigated potential transcriptional activities of SC1 and analyzed the function of its various domains. We show that SC1 acts as a transcriptional repressor when it is tethered to Gal4 DNA-binding domain. The repressive activity requires a trichostatin A–sensitive histone deacetylase (HDAC) activity, and SC1 is found in a complex with HDACs 1, 2, and 3. Transcriptional repression exerted by SC1 requires the presence of its zinc finger domains and the PR domain. Additionally, these two domains are involved in the efficient block of BrdU incorporation by SC1. The zinc finger domains are also necessary to direct SC1's nuclear localization. Lastly, SC1 represses the promoter of a promitotic gene, cyclin E, suggesting a mechanism for how growth arrest is regulated by SC1

    Factors associated with burnout among healthcare providers in a rural context, South Africa

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    Background: Healthcare providers (HCPs) are at risk of burnout in sub-Saharan Africa. However, there is little research in rural and primary care settings. Aim: To evaluate burnout and its associated factors among public sector HCPs in South Africa. Setting: Primary health care clinics, community health centres and district hospitals in Nkomazi Local Municipality, Mpumalanga province. Methods: Quantitative study design using a cross-sectional survey. Healthcare providers (n = 1139) working in Nkomazi Local Municipality were invited to participate. Burnout was assessed using the Maslach Burnout Inventory. A demographic and occupational questionnaire, the General Help-Seeking Questionnaire and the Health and Safety Executive Indicator Tool were used. Results: A total of 302 HCPs, between 23 and 61 years, mostly female (n = 252; 83.44%) and nurses (n = 235; 77.81%) participated. High burnout was observed for Emotional Exhaustion (median score 26 [IQR {interquartile range}: 34–16]) and Personal Accomplishment (median score 29 [IQR: 34–25]). Most participants (n = 215; 71.19%) would seek help if they had an emotional problem. Bivariate analysis revealed significant associations between workplace demands, control, management support, peer support, relationships, role and change with all subscales of burnout. Multivariate regression analysis found that Personal Accomplishment improved by 0.49 (95% CI: 0.10–0.89) for every point in improved work demands, by 0.84 (95% CI: 0.01–1.67) for every point towards improved management support and by 1.19 (95% CI: 0.48–1.90) for every point towards having an improved role. Conclusions: During 2022, HCPs working in a rural area in South Africa displayed high levels of burnout for Emotional Exhaustion and Personal Accomplishment but not for Depersonalisation. Contributions: Improvements in work demands, managerial support and role clarity may reduce burnout among HCP in a rural, primary care setting

    La influencia del biocomercio en la cadena de valor de exportación de la nuez del Brasil entre los años 2012 y 2019

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    El presente trabajo tiene como finalidad analizar la influencia del BioComercio en la cadena de valor de exportación de la nuez del Brasil entre los años 2012 y 2019. Se empleó una metodología de investigación mixta en la cual hicimos uso de distintas bases de datos numéricos, como SUNAT, Veritrade, Trademap; así como entrevistas a distintos gerentes de empresas, asociaciones y expertos/especialistas. En la parte inicial de la investigación se habla acerca de los antecedentes, tanto nacionales como internacionales, que permitieron crear una base para nuestra investigación. Además, se explican las bases teóricas que permiten explicar nuestra investigación. Se plantearon cuatro hipótesis para poder analizar la influencia del BioComercio en la cadena de valor de exportación de la nuez del Brasil, también conocida como castaña. Dentro de los resultados más importantes podemos mencionar que la nuez del Brasil es un fruto seco de la biodiversidad nativa y que cumple desde ya con la definición del BioComercio. Finalmente, presentaremos los resultados y análisis realizados a la cadena de valor de exportación de la nuez del Brasil, así como al BioComercio. Estos resultados incluyen figuras, tablas y cuadros con la relación de las variables antes mencionadas. El análisis se realizó junto con las respuestas de los entrevistados y con la recolección de datos, como el total FOB en millones de dólares, cantidades exportadas en toneladas y precios.The purpose of this research is to analyse the influence of BioTrade on the Brazilian nuts exports value chain between 2012 and 2019. A mixed research methodology were used, in which we made use of different numerical databases, such as SUNAT, Veritrade, Trademap; as well as interviews with different managers of companies, associations and experts/specialists. In the initial part of the investigation, we will talk about the national and international background that allowed us to create the basis for our investigation. In addition, it explains the theoretical bases that allow us to explain our research. Four hypotheses were proposed to be able to analyse the influence of BioTrade in the export value chain of the Brazilian nut. Among the most important results, we can assert that the Brazilian nut is a dried fruit of the native biodiversity and that it already complies with the definition BioTrade. Finally, we will present the results and analysis carried out on the Brazilian nuts exports value chain, as well as BioTrade. These results include figures, tables and descriptions of the relationship of the aforementioned variables. The analysis was carried out together with the responses of the interviewees and with the collection of data, such as total FOB in millions of dollars, quantities exported in tons and prices

    The Lilead Survey: A National Study of District-Level Library Supervisors: The Position, Office, and Characteristics of the Supervisor

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    The school district library supervisor occupies a pivotal position in library and information services programs that support and enhance the instructional efforts of a school district: providing leadership; advocating for the programs; supporting, advising, and providing professional development to building-level librarians; and representing school library programs to stakeholders in the school system and the community at large. With funding from the Institute of Museum and Library Services, the Lilead Project was founded at the University of Maryland in 2011 to study, support, and build community among school district library supervisors (Lilead Project n.d.). To gain a better understanding of supervisors--who they are, the duties they perform, and the challenges they face--and to establish baseline data upon which further research can be built, in 2012 the project team conducted a survey of supervisors nationwide: the Lilead Survey. In this paper, which is the first of two planned reports on the results of the survey, we present findings related to the position and office of the supervisor; demographic information, qualifications, and career paths of the incumbents of the position; and changes in policies, curriculum, and resources that impact the supervisor\u27s responsibilities for library services. Survey findings related to responsibilities and tasks assigned to the position, professional development needs of supervisors and staff, and challenges and needs that supervisors face will be presented in the second report

    The Lilead Survey: A National Study of District-Level Library Supervisors: Roles, Responsibilities, Challenges, and Professional Development Needs

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    The school district library supervisor plays a pivotal role in supporting, advising, and providing professional development to building-level librarians; advocating for the program; providing leadership; and representing school library programs to stakeholders in the school system and the larger community. To gain a better understanding of supervisors\u27 roles, responsibilities, demographics, and challenges, and to establish baseline data upon which further research can be built, the Lilead Project was initiated in 2011 at the University of Maryland with funding from the Institute of Museum and Library Services. In 2012 the project team conducted the Lilead Survey, a survey of supervisors nationwide. In this paper, the second of two reports on the results of the survey, we present findings related to the responsibilities and tasks assigned to the position, professional development needs of supervisors and staff, and the range of stakeholder groups with which supervisors work

    Gender-based differences in injecting drug use by young adults who experienced maltreatment in childhood: findings from an Australian birth cohort study

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    Background Childhood maltreatment has been associated with a range of adverse mental and psychosocial outcomes, but its association with subsequent injecting drug use (IDU) is less clear. This study investigates the associations between specific and multiple forms of substantiated childhood maltreatment and IDU reported at 21 years. Method The Mater-University of Queensland Study of Pregnancy is a prospective birth cohort study. It recruited pregnant women at their first antenatal clinic visit and collected data on their children at 21 years. Data from 3750 participants (1769 males and 1981 females) were analysed using agency substantiated childhood maltreatment from birth to 14 years of age and self-reports of ever IDU at 21 years. We used multivariable logistic regression analyses to control for possible confounders. Results The sample's mean age was 20.6 years. Some 4.1% (n\ua0=\ua072) of males and 4.6% (n\ua0=\ua091) of females had experienced substantiated childhood maltreatment. The prevalence of IDU was 6.6% (n\ua0=\ua0118) and 4.6% (n\ua0=\ua091) for males and females, respectively. In adjusted models, all forms of substantiated childhood maltreatment, with the exception of sexual abuse, were associated with IDU in females (adjusted odds ratios (AORs)\ua0=\ua02.69–3.02) but only emotional abuse (AOR\ua0=\ua02.51) was associated with IDU in males. Multiply occurring forms of childhood maltreatment were also associated with IDU in females (AORs\ua0=\ua02.36–3.41) but not in males. Conclusions Injecting drug use appears to be an adverse outcome of childhood maltreatment particularly in females. Additional research is needed to better understand why females appear to be more affected than males

    Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity

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    Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML

    Outcomes of bailout percutaneous ventricular assist device versus prophylactic strategy in patients undergoing nonemergent percutaneous coronary intervention

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    OBJECTIVES: To compare in-hospital outcomes of bailout support to prophylactic support with percutaneous ventricular assist devices (pVAD) for high-risk nonemergent percutaneous coronary intervention (HRPCI). BACKGROUND: Prophylactic support with pVAD for a HRPCI is used in patients felt to be at risk for hemodynamic collapse during PCI. An alternative strategy of bailout pVAD support in the event of hemodynamic collapse is also entertained. METHODS: We compared the outcomes of patients entered in the cVAD database who underwent Impella Protected PCI (ProPCI group) with patients from the cVAD and USpella databases receiving bailout Impella support for hemodynamic collapse during HRPCI (Bailout group). RESULTS: A total of 1,028 patients supported with Impella pVAD were entered into the cVAD database as of July 2019 and were included in this analysis. Of those 971 were in the ProPCI group and 57 in the Bailout group. Patients in the Bailout group were more often female (50.9%vs. 27.2%, p = .0002) with higher median baseline left ventricular ejection fraction (LVEF) (40%vs. 30%, p \u3c .0001) and with lower prevalence of both heart failure (42.1%vs. 56.9%, p = .0385) and left main disease (40.0%vs. 56.1%, p = .0250) compared to the ProPCI group. Unadjusted and adjusted in-hospital mortality was significantly higher in the Bailout group (49.1%vs. 4.3%, and 57.8%vs. 4.4%, p \u3c .0001 for both). CONCLUSIONS: In our study population, the bailout group was associated with significant increased mortality compared to ProPCI group. Female gender was more frequently observed in patients requiring bailout pVAD. Further investigation is warranted in order to generalize the findings of our study
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