179 research outputs found

    A role for ER-beta in the effects of Low-Density Lipoprotein Cholesterol and 27-hydroxycholesterol on Breast Cancer Progression:involvement of the IGF signalling pathway?

    Get PDF
    Cholesterol—in particular, high levels of low-density lipoprotein (LDL) and its metabolite, 27-hydroxycholesterol (27-OHC)—is correlated with increases in the risks of breast cancer and obesity. Although the high expression of LDL/27-OHC has been reported in breast cancer, its effects and mechanism of action remain to be fully elucidated. In this study, we found that the effects of LDL on cell proliferation were mediated by the activation of the cytochrome P450 enzyme, sterol 27 hydroxylase, and cholesterol 27-hydroxylase (CYP27A1) in both ER-α-positive and ER-α-negative breast cancer cells. We found that treatment with 27-OHC only increased cell growth in oestrogen receptor-α (ER-α)-positive breast cancer cells in an ER-α-dependent manner, but, interestingly, the effects of 27-OHC on cell migration and invasion were independent of ER-α. Using ER-α-negative MDA-MB-231 cells, we found that 27-OHC similarly promoted cell invasion and migration, and this was mediated by oestrogen receptor β (ER-β). These results suggest that 27-OHC promotes breast cancer cell proliferation in ER-α-positive breast cancer cells via ER-α, but migration and invasion are mediated via ER-β in ER-α positive and negative cell lines. The addition of LDL/27OHC increased the production of IGF-I and the abundance of IGF-IR in TNBC. We further found that modulating ER-β using an agonist or antagonist increased or decreased, respectively, levels of the IGF-I and EGF receptors in TNBC. The inhibition of the insulin-like growth factor receptor blocked the effects of cholesterol on cell growth and the migration of TNBC. Using TCGA and METABRIC microarray expression data from invasive breast cancer carcinomas, we also observed that higher levels of ER-beta were associated with higher levels of IGF-IR. Thus, this study shows novel evidence that ER-β is central to the effects of LDL/27OHC on invasion, migration, and the IGF and EGF axes. Our data suggest that targeting ER-β in TNBC could be an alternative approach for downregulating IGF/EGF signalling and controlling the impact of LDL in breast cancer patients

    Axiomatic/asymptotic evaluation of multilayered plate theories by using single and multi-points error criteria

    Get PDF
    AbstractThis paper deals with refined theories for multilayered composites plates. Layer-Wise (LW) and Equivalent Single Layer (ESL) theories are evaluated by means of axiomatic–asymptotic approach. Theories with forth order displacement fields in the thickness layer/plate direction z are implemented by referring to the Unified Formulation by Carrera. The effectiveness of each term of the made expansion is evaluated by comparing the related theories with a reference solution. As a result a reduced model is obtained which preserve the accuracy of the full-model (model that include the whole terms of the z-expansion) but it removes the not-significant terms in the same expansion (those terms that do no improve the results according to a given error criteria). Various single-point and multi-point error criteria have been analyzed and compared in order to establish such an effectiveness: error localized in an assigned point along z, error localized at each interface, error located at the z-value corresponding to the maximum value of the considered variables, etc. Applications are given in case of closed form solutions of orthotropic cross-ply, rectangular, simply supported plates loaded by bisinusoidal distribution of transverse pressure. Symmetrically and unsymmetrical laminated cases are considered along with sandwich plates. It is found the reduced model is strongly influenced by the used localized error and that in same case the reduced model which is obtained by of single point criteria can be very much improved by the use of multi-point criteria

    Assessed and discharged - diagnosis, mortality and revisits in short-term emergency department contacts

    Get PDF
    BACKGROUND: Emergency departments (EDs) experience an increasing number of patients. High patient flow are incentives for short duration of ED stay which may pose a challenge for patient diagnostics and care implying risk of ED revisits or increased mortality. Four hours are often used as a target time to decide whether to admit or discharge a patient. OBJECTIVE: To investigate and compare the diagnostic pattern, risk of revisits and short-term mortality for ED patients with a length of stay of less than 4 h (visits) with 4–24 h stay (short stay visits). METHODS: Population-based cohort study of patients contacting three EDs in the North Denmark Region during 2014–2016, excluding injured patients. Main diagnoses, number of revisits within 72 h of the initial contact and mortality were outcomes. Data on age, sex, mortality, time of admission and ICD-10 diagnostic chapter were obtained from the Danish Civil Registration System and the regional patient administrative system. Descriptive statistics were applied and Kaplan Meier mortality estimates with 95% CI were calculated. RESULTS: Seventy-nine thousand three hundred forty-one short-term ED contacts were included, visits constituted 60%. Non-specific diagnoses (i.e. symptoms and signs and other factors) were the most frequent diagnoses among both visits and short stay visits groups (67% vs 49%). Revisits were more frequent for visits compared to short stay visits (5.8% vs 4.2%). Circulatory diseases displayed the highest 0–48-h mortality within the visits and infections in the short stay visits (11.8% (95%CI: 10.4–13.5) and (3.5% (95%CI: 2.6–4.7)). 30-day mortality were 1.3% (95%CI: 1.2–1.5) for visits and 1.8% (95%CI: 1.7–2.0) for short stay visits. The 30-day mortality of the ED revisits with an initial visit was 1.0% (0.8–1.3), vs 0.7% (0.7–0.8) for no revisits, while 30-day mortality nearly doubled for ED revisits with an initial short stay visit (2.5% (1.9–3.2)). CONCLUSIONS: Most patients were within the visit group. Non-specific diagnoses constituted the majority of diagnoses given. Mortality was higher among patients with short stay visits but increased for both groups with ED revisits. This suggest that diagnostics are challenged by short time targets

    Bending Analysis of Functionally Graded Plates in the Context of Different Theories of Thermoelasticity

    Get PDF
    The quasistatic bending response is presented for a simply supported functionally graded rectangular plate subjected to a through-the-thickness temperature field under the effect of various theories of generalized thermoelasticity, namely, classical dynamical coupled theory, Lord and Shulman's theory with one relaxation time, and Green and Lindsay's theory with two relaxation times. The generalized shear deformation theory obtained by the first author is used. Material properties of the plate are assumed to be graded in the thickness direction according to a simple exponential law distribution in terms of the volume fractions of the constituents. The numerical illustrations concern quasistatic bending response of functionally graded square plates with two constituent materials are studied using the different theories of generalized thermoelasticit

    Sister Mary Joseph's Nodule at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 34 cases.

    Get PDF
    Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis

    Finite Element Analysis of Free Vibration of the Delaminated Composite Plate with Variable Kinematic Multilayered Plate Elements

    Get PDF
    Composite laminates are prone to delamination. Implementation of delamination in the Carrera Unified Formulation frame work using nine noded quadrilateral MITC9 element is discussed in this article. MITC9 element is devoid of shear locking and membrane locking. Delaminated as well as healthy structure is analyzed for free mode vibration. The results from the present work are compared with the available experimental or/and research article or/and the three dimensional finite element simulations. The effect of different kinds and different percentages of area of delamination on the first three natural frequencies of the structure is discussed. The presence of open-mode delamination mode shape for large delaminations within the first three natural frequencies is discussed. Also, the switching of places between the second bending mode, with that of the first torsional mode frequency is discussed. Results obtained from different ordered theories are compared in the presence of delamination. Advantage of layerwise theories as compared to equivalent single layer theories for very large delaminations is stated. The effect of different kinds of delamination and their effect on the second bending and first torsional mode shape is discussed. (C) 2014 Elsevier Ltd. All rights reserved
    • …
    corecore