The anticancer properties of dietary polyphenols and its relation with apoptosis

Aberrantly regulated apoptosis is involved in the pathogenesis of several diseases and defective apoptosis leads to uncontrolled cell proliferation and tumorigenesis. Cancer is an example of a pathologic condition where the normal mechanisms of cell cycle regulation are dysfunctional either by excessive cell proliferation, inhibited/suppressed apoptosis or both. Dietary habits are estimated to contribute to, at least, one third of all human cancers, showing that dietary components can exacerbate or interfere with carcinogenesis. However, several epidemiological studies have revealed that some dietary factors can decrease the risk of different types of cancer. Apoptosis is suggested to be a crucial mechanism for the chemopreventive properties associated with several dietary factors by eliminating potentially deleterious (damaged/mutated) cells. Food, a readily available item, contains several promising chemopreventive agents. Polyphenols are serious candidates since they are responsible for the cancer protective properties of a diet rich in vegetables and fruits: numerous phenolic compounds showed antiproliferative and cytotoxic effects, and more specifically pro-apoptotic activities, in several cancer cells lines and animal tumor models. The aim of the present review is to analyze and summarize several aspects related to the molecular mechanisms of apoptosis induced by dietary factors with particular emphasis on polyphenols. Dietary factors that can activate cell death signals and induce apoptosis, preferentially in precancerous or malignant cells, and the study of their apoptotic inducing targets can represent a mean to devise new strategies for cancer prevention in the future

The systematicity challenge to anti-representational dynamicism

After more than twenty years of representational debate in the cognitive sciences, anti-representational dynamicism may be seen as offering a rival and radically new kind of explanation of systematicity phenomena. In this paper, I argue that, on the contrary, anti-representational dynamicism must face a version of the old systematicity challenge: either it does not explain systematicity, or else, it is just an implementation of representational theories. To show this, I present a purely behavioral and representation-free account of systematicity. I then consider a case of insect sensorimotor systematic behavior: communicating behavior in honey bees. I conclude that anti-representational dynamicism fails to capture the fundamental trait of systematic behaviors qua systematic, i.e., their involving exercises of the same behavioral capacities. I suggest, finally, a collaborative strategy in pursuit of a rich and powerful account of this central phenomenon of high cognition at all levels of explanation, including the representational level

Algorithmic iteration for computational intelligence

Machine awareness is a disputed research topic, in some circles considered a crucial step in realising Artificial General Intelligence. Understanding what that is, under which conditions such feature could arise and how it can be controlled is still a matter of speculation. A more concrete object of theoretical analysis is algorithmic iteration for computational intelligence, intended as the theoretical and practical ability of algorithms to design other algorithms for actions aimed at solving well-specified tasks. We know this ability is already shown by current AIs, and understanding its limits is an essential step in qualifying claims about machine awareness and Super-AI. We propose a formal translation of algorithmic iteration in a fragment of modal logic, formulate principles of transparency and faithfulness across human and machine intelligence, and consider the relevance to theoretical research on (Super)-AI as well as the practical import of our results

Fibrinolysis or Primary PCI in ST-Segment Elevation Myocardial Infarction

BACKGROUNDIt is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI).METHODSAmong 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients >= 75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. the primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days.RESULTSThe primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P = 0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P = 0.04; after protocol amendment, 0.5% vs. 0.3%, P = 0.45). the rates of nonintracranial bleeding were similar in the two groups.CONCLUSIONSPrehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.)Boehringer IngelheimEli LillyMerckRocheDaiichi SankyoMedicines CompanyAstraZenecaSanofiBayerSchering-PloughSanofi-AventisBristol-Myers SquibbAbbottMedtronicEdwards LifesciencesServierPfizerUniv Alberta, Canadian Virtual Coordinating Ctr Global Collabor, Edmonton, AB, CanadaUniv Alberta, Mazankowski Alberta Heart Inst, Edmonton, AB, CanadaUniv Hosp Leicester Trust, Leicester Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester, Leics, EnglandUniv Nottingham, Dept Cardiovasc Med, Nottingham NG7 2RD, EnglandLille Univ Hosp, Emergency Dept, Lille, FranceLille Univ Hosp, SAMU, Lille, FranceBoehringer Ingelheim GmbH & Co KG, Reims, FranceCtr Hosp Versailles, SAMU 78, Versailles, FranceMobile Intens Care Unit, Versailles, FranceFirst Moscow State Med Univ, Dept Internal Dis, Moscow, RussiaEmpresa Publ Emergencias Sanitarias, Almeria, SpainUniv Belgrade, Sch Med, Belgrade, SerbiaUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniv Athens, Dept Cardiol 3, GR-10679 Athens, GreeceBenjamin Franklin Med Ctr, Charite, Berlin, GermanyUniv Oslo, Ulleval Hosp, Dept Cardiol, Oslo, NorwayWilhelminenhosp, Dept Med Cardiol & Emergency Med 3, Vienna, AustriaPoznan Univ Med Sci, Dept Cardiol, Poznan, PolandAzienda Osped Univ Udine, Dept Cardiothorac Sci, Udine, ItalyBoehringer Ingelheim GmbH & Co KG, Biberach, GermanyBoehringer Ingelheim GmbH & Co KG, Basel, SwitzerlandKatholieke Univ Leuven, Dept Cardiovasc Sci, B-3000 Louvain, BelgiumKatholieke Univ Leuven, Interuniv Inst Biostat & Stat Bioinformat, B-3000 Louvain, BelgiumUniv Hasselt, Hasselt, BelgiumUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilWeb of Scienc

The Left Ventricular Dysfunction Questionnaire: Italian translation and validation.

Patients affected by heart failure have a compromised quality of life (QOL) and in the last few years "health related quality of life" has become an important outcome indicator for the evaluation of heart failure treatment. Methods: Translation into Italian of the Left Ventricular Dysfunction Questionnaire (LVD-36), a new, 36-item, disease-specific health status instrument for patients with congestive heart failure, and its subsequent validation by administration to 50 consecutive patients in our heart failure outpatient clinic. The Italian LVD-36 was compared to the "The Minnesota Living with Heart Failure Questionnaire" (MLHF). Results: The Italian version of the LVD-36 correlates well with MLHF for ejection fraction (EF), NYHA class I and II, etiology and therapy. Since, however, the LVD-36 has only one domain, it may be able to offer more synthetic information than MLHF about patients' status. Conclusions: The Italian version of the LVD-36 appears to be a reliable instrument for assessing patients' QOL and the degree of limitations imposed on them by the disease. It is short, clear and easy to complete. In patients with heart failure the LVD-36 correlates well with the MLHF and may be considered a new disease- specific instrument to estimate changes in health status, and an useful support in optimizing therapeutic options

Characterization and applications of a Crimean-Congo hemorrhagic fever virus nucleoprotein-specific Affimer: Inhibitory effects in viral replication and development of colorimetric diagnostic tests

Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera