481 research outputs found

    Successful Implementation of Pharmacy Retail Store Loyalty Reward Programs

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    Loyalty reward programs are utilized within various industries as a key marketing strategy. A successfully implemented loyalty reward program benefits both the consumer and the company. The purpose of this multicase study was to explore strategies that pharmacy retail managers use to deliver loyalty reward programs. The theory of planned behavior was used as the conceptual framework to guide the study. Mobile technology, customer involvement, brand management, and tier-based rewards were the themes that emerged during data analysis. The findings are of interest to pharmacy retail managers and marketers because they are instrumental in implementing a successful loyalty reward program

    High school EFL students’ beliefs about oral corrective feedback: The role of gender, motivation and extraversion

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    This study employed an explanatory sequential mixed-methods research design to examine the beliefs of Vietnamese EFL students concerning oral corrective feedback (CF) and the role of some individual differences in these beliefs. The data consisted of questionnaires completed by 250 Vietnamese high school students and follow-up interviews with 15 of them. Exploratory factor analysis revealed six latent factors underlying students’ beliefs about CF, namely, (1) output-prompting CF and eliciting recasts, (2) desire for CF, (3) non-verbal cues, (4) important errors, (5) input-providing CF, and (6) less important errors. Descriptive statistics and thematic analysis of the interviews showed that students were positive about CF. They liked both input-providing CF and output-prompting CF for all error types. Metalinguistic feedback was the most strongly preferred, while clarification request was the least preferred. Further statistical analyses revealed some interesting relationships between students’ beliefs about CF and their gender, English learning motivation, and self-rated introversion/extraversion. Females were more positive about CF than males, and extraverted females were more positive about input-providing CF than introverted females. Also, students learning English for exams were more positive about CF than those learning English for communication. Pedagogical implications for effective feedback provision in EFL contexts are discussed

    A non-apoptotic role for caspase-9 in muscle differentiation

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    Caspases, a family of cysteine proteases most often investigated for their roles in apoptosis, have also been demonstrated to have functions that are vital for the efficient execution of cell differentiation. One such role that has been described is the requirement of caspase-3 for the differentiation of skeletal myoblasts into myotubes but, as yet, the mechanism leading to caspase-3 activation in this case remains elusive. Here, we demonstrate that caspase-9, an initiator caspase in the mitochondrial death pathway, is responsible for the activation of caspase-3 in differentiating C2C12 cells. Reduction of caspase-9 levels, using an shRNA construct, prevented caspase-3 activation and inhibited myoblast fusion. Myosin-heavy-chain expression, which accompanies myoblastic differentiation, was not caspase-dependent. Overexpression of Bcl-xL, a protein that inhibits caspase-9 activation, had the same effect on muscle differentiation as knockdown of caspase-9. These data suggest that the mitochondrial pathway is required for differentiation; however, the release of cytochrome c or Smac (Diablo) could not be detected, raising the possibility of a novel mechanism of caspase-9 activation during muscle differentiation.</jats:p

    Distinct Clinical and Pathological Features Are Associated with the BRAFT1799A(V600E) Mutation in Primary Melanoma

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    The BRAFT1799A mutation encodes BRAFV600E that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAFT1799A mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAFT1799A mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAFT1799A mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAFT1799A mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); ≤50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAFT1799A mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAFT1799A mutation is associated with a lower rate of tumor proliferation

    Chemokine (C-C motif) ligand 2 mediates direct and indirect fibrotic responses in human and murine cultured fibrocytes

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    <p>Abstract</p> <p>Background</p> <p>Fibrocytes are a population of circulating bone-marrow-derived cells that express surface markers for leukocytes and mesenchymal cells, and are capable of differentiating into myofibroblasts. They have been observed at sites of active fibrosis and increased circulating numbers correlate with mortality in idiopathic pulmonary fibrosis (IPF). Inhibition of chemokine (C-C motif) receptor 2 (CCR2) during experimental models of lung fibrosis reduces lung collagen deposition, as well as reducing lung fibrocyte accumulation. The aim of the present study was to determine whether human and mouse fibrocytes express functional CCR2.</p> <p>Results</p> <p>Following optimized and identical human and murine fibrocyte isolation, both cell sources were shown to be positive for CCR2 by flow cytometry and this expression colocalized with collagen I and CD45. Human blood fibrocytes stimulated with the CCR2 ligand chemokine (C-C motif) ligand 2 (CCL2), demonstrated increased proliferation (<it>P </it>< 0.005) and differentiation into myofibroblasts (<it>P </it>< 0.001), as well as a chemotactic response (<it>P </it>< 0.05). Murine fibrocytes also responded to CCR2 stimulation, with CCL12 being more potent than CCL2.</p> <p>Conclusions</p> <p>This study directly compares the functional responses of human and murine fibrocytes to CCR2 ligands, and following comparable isolation techniques. We have shown comparable biological effects, strengthening the translatability of the murine models to human disease with respect to targeting the CCR2 axis to ameliorate disease in IPF patients.</p

    The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43

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    Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups of neurodegenerative disease. Kinase hyperactivity may be a consistent feature of ALS and FTLD-TDP, as phosphorylated TDP-43 is not observed in the absence of neurodegeneration. By examining changes in TDP-43 phosphorylation state, we have identified kinases controlling TDP-43 phosphorylation in a C. elegans model of ALS. In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes. Using refined methodology, we demonstrate TTBK1 and TTBK2 directly phosphorylate TDP-43 in vitro and promote TDP-43 phosphorylation in mammalian cultured cells. TTBK1/2 overexpression drives phosphorylation and relocalization of TDP-43 from the nucleus to cytoplasmic inclusions reminiscent of neuropathologic changes in disease states. Furthermore, protein levels of TTBK1 and TTBK2 are increased in frontal cortex of FTLD-TDP patients, and TTBK1 and TTBK2 co-localize with TDP-43 inclusions in ALS spinal cord. These kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as ALS and FTLD-TDP

    Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines

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    Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles—the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation—with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature

    Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort

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    To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time. We studied 1700 patients with a mean (s.d.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis. GCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SL

    The Impact of HIV, an Antiretroviral Programme and Tuberculosis on Mortality in South African Platinum Miners, 1992–2010

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    HIV and tuberculosis (TB) are the most common causes of death in South Africa. Antiretroviral therapy (ART) programmes should have had an impact on mortality rates. This study describes the impact of HIV, a Wellness (HIV/ART) programme and TB on population-wide trends in mortality and causes of death among South African platinum miners, from before the HIV epidemic into the ART era
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