In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate,

The growth inhibitory effects of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) were tested on three long-established endometrial carcinoma cell lines (HEC-1, KLE, and RL95-2) and on UM-EC-1, a new endometrial carcinoma cell line established in our laboratory. MPA and TAM were used in growth experiments either alone, simultaneously, or sequentially. The MCF-7 breast cancer cell line was used as a control. None of the endometrial carcinoma cell lines showed significant sensitivity to 0.1-10 [mu]M MPA. In contrast, 10 days exposure to 5 [mu]M TAM induced 83 and 70% growth inhibition in HEC-1 and KLE cultures, whereas the growth of UM-EC-1 was inhibited by 99.7% and RL95-2 cultures by 100%. TAM-induced growth inhibition was reversible since all cell lines resumed logarithmic growth when TAM was removed from the culture medium. Addition of 17-[beta]-estradiol (E2) to the culture medium did not accelerate recovery, and reversal of TAM-induced growth inhibition was not seen when TAM and E2 were added simultaneously. This is consistent with our finding that, except for MCF-7, these cell lines did not show detectable estrogen receptor (ER) activity in assays performed at the time of these experiments. When treated sequentially with TAM and MPA, all cell lines resumed logarithmic growth when medium containing TAM was replaced with medium containing MPA. Simultaneous exposure to 5 [mu]M MPA and 5 [mu]M TAM resulted in a slight additive growth inhibitory effects only in KLE cultures. Our results show that MPA does not have growth inhibitory effects in these endometrial carcinoma cell cultures, whereas TAM exerts a potent growth inhibitory effect that is not reversed by estrogen and may thus be mediated through a mechanism different from blockade of ER. In vitro results with the UM-EC-1 cell line correlated with the clinical response of the cell line donor. Her disease progressed during postoperative MPA therapy, but subsequently she responded to TAM therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27275/1/0000291.pd

Appendicolith appendicitis is clinically complicated acute appendicitis – is it histopathologically different from uncomplicated acute appendicitis

Purpose: Acute appendicitis may present as uncomplicated and complicated and these disease forms differ both epidemiologically and clinically. Complicated acute appendicitis has traditionally been defined as an appendicitis complicated by perforation or a periappendicular abscess, and an appendicolith represents a predisposing factor of complicated disease. There are histopathological differences between uncomplicated acute appendicitis and the previously established traditional forms of complicated acute appendicitis, but to our knowledge, the histopathological differences between uncomplicated acute appendicitis and complicated acute appendicitis presenting with an appendicolith have not yet been reported. The study purpose was to assess these differences with two prospective patient cohorts: (1) computed tomography (CT) confirmed uncomplicated acute appendicitis patients enrolled in the surgical treatment arm of the randomized APPAC trial comparing appendectomy with antibiotics for the treatment of uncomplicated acute appendicitis and (2) patients with CT-verified acute appendicitis presenting with an appendicolith excluded from the APPAC trial.Methods: The following histopathological parameters were assessed: appendiceal diameter, depth of inflammation, micro-abscesses, density of eosinophils, and neutrophils in appendiceal wall and surface epithelium degeneration.Results: Using multivariable logistic regression models adjusted for age, gender, and symptom duration, statistically significant differences were detected in the depth of inflammation = 150/mm(2) (adjusted OR 0.97 (95%CI: 0.95-0.99, p=0.013), adjusted OR 3.04 (95%CI: 1.82-5.09, pConclusions: These results corroborate the known clinical association of an appendicolith to complicated acute appendicitis.</div

Adaptation of an Evaluation System for e-Health Environments

Proceedings of: 14th International Conference, KES 2010, Cardiff, UK, September 8-10, 2010The increase in ageing of European population implies a high cost in economy and society in any European country and it can be reduced if we pay attention and develop home care systems. Evaluation of these systems is a critical and challenging issue but seldom tackled. It is important before evaluating a system to figure out what is the evaluation goal. In our case, such a goal is to evaluate enhanced user experience and beyond the evaluation goal it is also a central concern about what to evaluate. In this paper we propose a multi-agent home care system where we describe how agents coordinate their decisions to provide e-services to patients when at home after hospitalization. Finally we center our proposal on the adaptation of an evaluation system, previously developed, to support the challenges of an e-Health environment and also the multi-user evaluation. These evaluation methods (online/offline) will provide user's (patients, patient's relatives and healthcare professionals) feedback into the system.This work was supported in part by Projects CICYT TIN2008-06742-C02-02/ TSI, CICYT TEC2008-06732-C02-02/TEC, CAM CONTEXTS (S2009/ TIC-1485) and DPS2008-07029-C02-02.Publicad

Emotions in business-to-business service relationships

Emotion in business-to-business service relationships regarding cargo services is explored. The service relationship is characterised by mutual trust and cooperation. Contact is mainly via telephone or e-mail with some face-to-face interactions and participants providing a complex, multi-skilled seamless service. Experience rather than training plays a vital role with long-term service relationships built up and maintained. Emotional sensitivity is acquired partly by experience and a repeat customer base but mainly through a genuine desire to help and get to know others. In contrast to the view of emotional labour bringing managerial control or adverse affects to service staff, the emotion engendered by this work is authentic expression bringing personal satisfaction

Operationalizing Co-Production in Public Services Delivery: The contribution of service blueprinting

We have argued for public services to move away from product-dominant logic towards a service approach. By taking a services orientation, the experience, inter-organizational, and systemic nature of public services delivery can be considered along with the role of the service user as a co-producer. In this article, we unpack how co-production can be operationalized through the application of service blueprinting. This article presents an example within higher education where the creation of a blueprint brought together staff and students to focus on the design of student enrolment, resulting in improved student experience and supporting co-production

Fish, Fish-Derived n-3 Fatty Acids, and Risk of Incident Atrial Fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study

Results of observational and experimental studies investigating the association between intake of long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) have been inconsistent.We studied the association of fish and the fish-derived n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with the risk of incident AF in individuals aged 45-64 from the Atherosclerosis Risk in Communities (ARIC) cohort (n = 14,222, 27% African Americans). Intake of fish and of DHA and EPA were measured via food frequency questionnaire. Plasma levels of DHA and EPA were measured in phospholipids in a subset of participants (n = 3,757). Incident AF was identified through the end of 2008 using ECGs, hospital discharge codes and death certificates. Cox proportional hazards regression was used to estimate hazard ratios of AF by quartiles of n-3 PUFAs or by fish intake.During the average follow-up of 17.6 years, 1,604 AF events were identified. In multivariable analyses, total fish intake and dietary DHA and EPA were not associated with AF risk. Higher intake of oily fish and canned tuna was associated with a nonsignificant lower risk of AF (p for trend = 0.09). Phospholipid levels of DHA+EPA were not related to incident AF. However, DHA and EPA showed differential associations with AF risk when analyzed separately, with lower risk of AF in those with higher levels of DHA but no association between EPA levels and AF risk.In this racially diverse sample, dietary intake of fish and fish-derived n-3 fatty acids, as well as plasma biomarkers of fish intake, were not associated with AF risk

Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution

Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models

Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling

Examining the impact of digital technologies on students’ Higher Education outcomes:The case of the Virtual Learning Environment and social media

Digital natives is a term used to describe current higher education (HE) students, whose lives are proliferated by digital technologies. To cater to the needs of this new generation of students, HE institutions increasingly adopt digital tools such as virtual learning environments (VLE) and social media (SM). Little is known, however, about the impact of these digital technologies on students’ HE outcomes. Drawing from service productivity theories, this study aims to address this gap. Through exploratory sequential mixed research methods, we identify five HE outcomes and reveal that Learning-Oriented Outcomes are the most important in HE even when digital technologies are not used; and these outcomes are further enhanced when students use VLE. Learning-Oriented Outcomes, however, are the least important when SM is used in HE; students tend to prioritise outcomes related to Knowledge Transfer instead. Our research findings derive theoretical and practical contributions and open up avenues for future research