Endocrine Active Compounds: From Biology to Dose Response Assessment

Histone deacetylase (HDAC) inhibitors target key steps of tumor development: They inhibit proliferation, induce differentiation and/or apoptosis, and exhibit potent antimetastatic and antiangiogenic properties in transformed cells in vitro and in vivo. Preliminary studies in animal models have revealed a relatively high tumor selectivity of HDAC inhibitors, strenghtening their promising potential in cancer chemotherapy. Until now, preclinical in vitro research has almost exclusively been performed in cancer cell lines and oncogene-transformed cells. However, as cell proliferation and apoptosis are essential for normal tissue and organ homeostasis, it is important to investigate how HDAC inhibitors influence the regulation of and interplay between proliferation, differentiation, and apoptosis in primary cells as well. This review highlights the discrepancies in molecular events triggered by trichostatin A, the reference compound of hydroxamic acid-containing HDAC inhibitors, in hepatoma cells and primary hepatocytes (which are key targets for drug-induced toxicity). The implications of these differential outcomes in both cell types are discussed with respect to both toxicology and drug development. In view of the future use of HDAC inhibitors as cytostatic drugs, it is highly recommended to include both tumor cells and their healthy counterparts in preclinical developmental studies. Screening the toxicological properties of compounds early in their development process, using a battery of different cell types, will enable researchers to discard those compounds bearing undesirable adverse activity before entering into expensive clinical trials. This will not only reduce the risk for harmful exposure of patients but also save time and money.     

Nawracające zapalenie opłucnej jako wiodący objaw rodzinnej gorączki śródziemnomorskiej

Familial Mediterranean Fever (FMF) is a disease with an autosomal recessive inheritance affecting inhabitants of the Mediterranean Sea basin area. It is the most prevalent fever-inflammatory syndrome manifested by fever episodes, serositis and rash. The symptoms regress spontaneously and between recurrent attacks of fever the child is healthy. Amyloidosis is the most serious complication. A case of a 8 year-old boy, a son of Armenian immigrants, with recurrent pleuritis is presented.     

Condition-Specific Pamphlets to Improve End-of-life Communication in Long-term Care: Staff Perceptions on Usability and Use

Objectives

This article reports findings on the usability and staff use of 5 condition- specific pamphlets of high prevalence in long-term care (LTC): dementia, heart failure, chronic obstructive pulmonary disease, renal failure, and frailty. The pamphlets were created in response to residents', families', and staff's recommendations for activating early reflections and communication about end-of-life care.

Resilience of African migrants: An integrative review

African migrant women represent a rapidly growing cohort of new arrivals in many countries. Many of these women demonstrate strength and resilience throughout the stressful migration process. In this integrative review, we explore the literature on African migrants' resilience using an ecological framework. Nine peer-reviewed journal articles and six grey literature documents were reviewed. Key internal and external factors in achieving resilience were identified, discussed, and diagrammatically represented using Bronfenbrenner's Ecological Framework under micro-, meso-, exo-, and macro-levels. Our findings show that the capacity for resilience demonstrated during migration could have implications for policy and practice.     

Primary hepatocyte cultures as in vitro tools for toxicity testing: quo vadis?

Cultures of primary hepatocytes are versatile tools that can serve many in vitro toxicity testing purposes. However, they cope with dedifferentiation, a process that is already initiated during the hepatocyte isolation procedure and that is manifested as the progressive loss of functionality upon subsequent cultivation. A number of strategies to prevent dedifferentiation have been introduced over the last decades, all which aim at re-establishing the in vivo hepatocyte micro-environment in vitro, but that are of merely limited success. Recent mechanistic insight into the mechanisms that underlie hepatocyte dedifferentiation has opened new avenues for the development of novel approaches that target the actual causes of this deteriorative process and thus for the generation of a long-term hepatic in vitro tool. Such experimental system is urgently needed, especially in the light of the stringent European legislative modifications that are currently encountered by the pharmaceutical, chemical and, particularly, the cosmetic industry.     

The use of narrative analysis to study transformative learning in associate degree nursing students: a focus on the methodology

The aim of this article is to describe the use of narrative inquiry as the research method used to investigate the transformative learning experiences of associate degree nursing students. The process of participant selection and recruitment, data collection and analysis, and development of narrative threads is defined. Implications for use of narrative inquiry in associate degree nursing education are explored. The traditional use of narratives in nursing education and practice is also defined.     

Does Tweeting Improve Citations? One-Year Results From the TSSMN Prospective Randomized Trial

1. Download : Download high-res image (181KB)
2. Download : Download full-size image

     

Estratificación basal de riesgo en pacientes mayores de 75 años con infarto y shock cardiogénico referidos para angioplastia primaria

Background and objectivesPatients older than 75 years with ST-segment elevation myocardial infarction undergoing primary angioplasty in cardiogenic shock have high mortality. Identification of preprocedural predictors of short- and long-term mortality could be useful to guide decision-making and further interventions.MethodsWe analyzed a nationwide registry of primary angioplasty in the elderly (ESTROFA MI + 75) comprising 3576 patients. The characteristics and outcomes of the subgroup of patients in cardiogenic shock were analyzed to identify associated factors and prognostic predictors in order to derive a baseline risk prediction score for 1-year mortality. The score was validated in an independent cohort.ResultsA total of 332 patients were included. Baseline independent predictors of mortality were anterior myocardial infarction (HR 2.8, 95%CI, 1.4-6.0; P = .005), ejection fraction < 40% (HR 2.3, 95%CI, 1.14-4.50; P = .018), and time from symptom onset to angioplasty > 6 hours (HR 3.2, 95%CI, 1.6-7.5; P = .001). A score was designed that included these predictive factors (score “6-ANT-40”). Survival at 1 year was 54.5% for patients with score 0, 32.3% for score 1, 27.4% for score 2 and 17% for score 3 (P = .004, c-statistic 0.70). The score was validated in an independent cohort of 124 patients, showing 1-year survival rates of 64.5%, 40.0%, 28.9%, and 22.2%, respectively (P = .008, c-statistic 0.68).ConclusionsA preprocedural score based on 3 simple clinical variables (anterior location, ejection fraction < 40%, and delay time > 6 hours) may be used to estimate survival after primary angioplasty in elderly patients with cardiogenic shock and to guide preinterventional decision-making.