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 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

Fibulin-1 is required for morphogenesis of neural crest-derived structures

AbstractHere we report that mouse embryos homozygous for a gene trap insertion in the fibulin-1 (Fbln1) gene are deficient in Fbln1 and exhibit cardiac ventricular wall thinning and ventricular septal defects with double outlet right ventricle or overriding aorta. Fbln1 nulls also display anomalies of aortic arch arteries, hypoplasia of the thymus and thyroid, underdeveloped skull bones, malformations of cranial nerves and hemorrhagic blood vessels in the head and neck. The spectrum of malformations is consistent with Fbln1 influencing neural crest cell (NCC)-dependent development of these tissues. This is supported by evidence that Fbln1 expression is associated with streams of cranial NCCs migrating adjacent to rhombomeres 2–7 and that Fbln1-deficient embryos display patterning anomalies of NCCs forming cranial nerves IX and X, which derive from rhombomeres 6 and 7. Additionally, Fbln1-deficient embryos show increased apoptosis in areas populated by NCCs derived from rhombomeres 4, 6 and 7. Based on these findings, it is concluded that Fbln1 is required for the directed migration and survival of cranial NCCs contributing to the development of pharyngeal glands, craniofacial skeleton, cranial nerves, aortic arch arteries, cardiac outflow tract and cephalic blood vessels

DSM-5 insomnia disorder in pregnancy: associations with depression, suicidal ideation, and cognitive and somatic arousal, and identifying clinical cutoffs for detection

STUDY OBJECTIVES: The study had three primary goals. First, we estimated survey-assessed DSM-5 insomnia disorder rates in pregnancy, and described associated sociodemographics, and sleep-wake and mental health symptoms. Second, we derived cutoffs for detecting DSM-5 insomnia disorder using common self-report measures of sleep symptoms. Third, we identified clinically relevant cut-points on measures of nocturnal cognitive and somatic arousal. METHODS: Ninety-nine women (85.9% in the 2nd trimester) completed online surveys including DSM-5 insomnia disorder criteria, the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Presleep Arousal Scale’s Cognitive (PSASC) and Somatic (PSASS) factors, and Edinburgh Postnatal Depression Scale. RESULTS: DSM-5 insomnia disorder rate was 19.2%. Insomnia was associated with depression, suicidality, nocturnal cognitive and somatic arousal, and daytime sleepiness. An ISI scoring method that aligns with DSM-5 criteria yielded excellent metrics for detecting insomnia disorder and good sleep. Regarding quantitative cutoffs, ISI ≥ 10 and ISI ≥ 11 (but not ISI ≥ 15) were supported for detecting DSM-5 insomnia, whereas ISI ≤ 7 and ISI ≤ 9 performed well for detecting good sleep. PSQI cutoff of 5 was supported for detecting insomnia and good sleep. The optimal cutoff for nocturnal cognitive arousal was PSASC ≥ 18, whereas the optimal cutoff for somatic arousal was PSASS ≥ 13. CONCLUSIONS: Insomnia disorder affects a large segment of pregnant women. Empirically derived cutoffs for insomnia, good sleep, cognitive arousal, and somatic arousal may inform case identification and future perinatal sleep research methodology

Proceso de re-diseño de un prototipo doméstico de precipitador electrostático tubular

El principal problema para el desarrollo de precipitadores electrostáticos cilíndricos [1] es que el gas sucio atraviesa el interior prototipo, donde se encuentran alojados los elementos que sujetan el electrodo emisor de campo eléctrico, por lo que, durante su funcionamiento, la alta concentración de partículas de combustión, sumada a la gran turbulencia en el interior de la tubería hace que se formen capas de partículas que cubren la totalidad del área interna de la tubería, creando problemas de descarga del campo. Esta capa de partículas es conductora (de hecho es precisamente esa la propiedad que se aprovecha para su retención), por lo que cuando el nivel de ensuciamiento llega a un punto crítico, se establece una capa de partículas entre los electrodos en la zona de entrada de humo y la electricidad fluye a través de la capa desde el electrodo emisor hasta el electrodo colector, sin que llegue a formarse el campo eléctrico de carga, impidiendo por tanto la carga y retención de las partículas durante cortos periodos de tiempo, insuficientemente largos como para aguantar las tandas de funcionamiento de las máquinas térmicas domésticas más comunes. Para solucionar el problema, se modifica el diseño de la conducción donde tiene lugar la retención, [2] para evitar el paso de gas sucio por las zonas sensibles donde tienen lugar la gestión de los dispositivos de carga de las partículas. El nuevo diseño está constituido por una innovadora doble T a 135º de acero soldado calorifugado, de tal manera que se disponga de cuatro ramales que permitan gestionar el humo y el electrodo por separado: • Dos ramales inferiores: uno para la entrada del gas y otro separado para el alojamiento del montaje y centrado inferior del electrodo. • Dos ramales superiores: uno para la salida del gas y otro separado y enfrentado con el de alojamiento inferior que garantice la tensión y el centrado correctos del electrodo emisor. De ese modo, las partículas contenidas en el gas entran directamente a la zona de carga y se depositan a lo largo de la zona recta, donde el campo eléctrico es más intenso, sin que se amontonen en las cavidades próximas al alojamiento del electrodo y se formen los anteriormente citados puentes. En el re-diseño juegan un papel fundamental el uso de materiales estándar, la consecución de un buen acabado interior para evitar el cebado de arcos voltaicos hacia las imperfecciones del metal, y la combinación de una buena masa metálica de descarga con un diseño modular, sencillo y seguro.Los autores agradecen el apoyo financiero del Ministerio de Economía y Competitividad a través del proyecto ENE2012-3640