THROMBOLYTIC THERAPY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

It is reported that the implementation in clinical practice thrombolytic (fibrinolytic) therapy resulted inmortality reduction during firstmonth after myocardial infarction from 17-18% to 5-8%. Different details of this therapy are considered: terms of thrombolysis since the beginning of myocardial infarction, alternative methods of coronary blood flow recovery , indications and contraindications, complications and side effects, estimation of thrombolysis efficacy. Fibrin-selective and fibrin-non-selective drugs are presented. Different fibrinolytics are described: streptokinase, anistreplase, alteplase, reteplase, tenekteplase. The results of large randomized clinical trials devoted to fibrinolytic therapy of myocardial infarction are analyzed: GISSI, ISSIS, TIMI, GUSTO, INJECT, ASSENT. The possibility to increase in efficacy and safety of fibrinolytics by their combination with acetylsalicylic acid, IIb/IIIa receptor inhibitors and heparins are discussed

The Challenge to Care in a Premier League Football Club

Elite men’s football in the UK has previously been portrayed as a harsh and competitive micro-political environment. This environment has been described as ‘uncaring’. Paradoxically, care has been identified as an essential aspect of coaching pedagogy. Thus, this study drew upon the experience of a case-study strength and conditioning coach to explore care in a Premier League Football Club. Specifically, a naturally occurring reflective diary served as a primary data source. Findings revealed that the coach ‘cared for’ an athlete through a ‘rules based’ approach, which thus far has not been described within coaching research. The narrative presented also suggested that care was constrained by the competitive context in which the coach operates. This context requires coaches to ‘care about’ results, and the associated implications for their own careers and other individuals around the club e.g. staff and supporters. Thus, this caring relationship was situated and influenced by wider contextual influences. This study should prompt significant consideration by coaches who might examine how their care is influenced by social, economic and micro-political factors, whilst simultaneously providing novel insights for coaching researchers who may further consider ‘rule based’ approaches to care. Keywords: Care; Elite Football; Coaching; Noddings; Micro-Politic

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project

Purpose: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). Methods: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. Results: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. Conclusion: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice

The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

BACKGROUND: The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT). METHODS: Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients. RESULTS: High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression. CONCLUSIONS: These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Evolution and Dynamics of Small RNA Response to a Retroelement Invasion in Drosophila

Although small RNAs efficiently control transposition activity of most transposons in the host genome, such an immune system is not always applicable against a new transposon's invasions. Here, we explored a possibility to introduce potentially mobile copy of the Penelope retroelement previously implicated in hybrid dysgenesis syndrome in Drosophila virilis into the genomes of two distant Drosophila species. The consequences of such introduction were monitored at different phases after experimental colonization as well as in D. virilis species, which is apparently in the process of ongoing Penelope invasion. We investigated the expression of Penelope and biogenesis of Penelope-derived small RNAs in D. virilis and D. melanogaster strains originally lacking active copies of this element after experimental Penelope invasion. These strains were transformed by constructs containing intact Penelope copies. We show that immediately after transformation, which imitates the first stage of retroelement invasion, Penelope undergoes transposition predominantly in somatic tissues, and may produce siRNAs that are apparently unable to completely silence its activity. However, at the later stages of colonization Penelope copies may jump into one of the piRNA-clusters, which results in production of homologous piRNAs that are maternally deposited and can silence euchromatic transcriptionally active copies of Penelope in trans and, hence, prevent further amplification of the invader in the host genome. Intact Penelope copies and different classes of Penelope-derived small RNAs were found in most geographical strains of D. virilis collected throughout the world. Importantly, all strains of this species containing full-length Penelope tested do not produce gonadal sterility in dysgenic crosses and, hence, exhibit neutral cytotype. To understand whether RNA interference mechanism able to target Penelope operates in related species of the virilis group, we correlated the presence of full-length and potentially active Penelope with the occurrence of piRNAs homologous to this transposable element in the ovaries of species comprising the group. It was demonstrated that Penelope-derived piRNAs are present in all virilis group species containing full-length but transcriptionally silent copies of this element that probably represent the remnants of its previous invasions taking place in the course of the virilis species divergent evolution

What's wrong with democracy at the moment, and why it matters for research and education

The article provides historical and political background to contemporary issues facing education and research. In doing so, it argues that there has been a fundamental inversion of democracy. What this means is that instead of democracy providing a political framework for the voices of people, it is employed as a cover for the interests of the wealthy. The article explores this inversion, drawing upon the theoretical insights of the Annaliste school of history and its contemporary expression in the work of such people as David Harvey and Immanuel Wallerstein. It is argued that, rather than an effective public historically emerging, there is what Walter Lipmann in 1927 called a 'phantom public' whose views, beliefs and conduct are open to manipulation. He called it the 'manufacture of consent'. The article explores the implications of the transformations of the economic and political scenes in conjunction with this shaping of public opinion for both research and education