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    ROLE OF BIOACTIVE-RICH DIET IN THE MODULATION OF RISK FACTORS FOR CHRONIC-DEGENERATIVE DISEASES: IN VIVO AND EX VIVO APPROACHES

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    Il rapido aumento dell’incidenza delle malattie cronico-degenerative è probabilmente uno dei maggiori problemi di sanità pubblica attuali. Sono numerosi gli studi che supportano il ruolo che determinati modelli alimentari ricchi in specifici alimenti o composti bioattivi hanno nella riduzione del rischio di sviluppare malattie. L’intervento di tipo nutrizionale è sempre più considerato una strategia di prevenzione primaria che risulta tra le più efficaci, convenienti e facilmente perseguibili. Recentemente, un interesse crescente si sta sempre più focalizzando su interventi dietetici personalizzati accuratamente studiati per soddisfare le specifiche esigenze nutrizionali di gruppi di popolazione target. Infatti, un approccio nutrizionale personalizzato sembra essere molto più efficace nell’ottenimento di uno specifico risultato, soprattutto in quei gruppi di popolazione target considerati più a rischio di sviluppare malattie croniche. Sulla base di queste premesse, lo scopo della presente tesi di dottorato è stato quello di valutare, attraverso approcci in vivo ed ex vivo, l'effetto del consumo di specifici alimenti e dei loro composti bioattivi nella modulazione di alcuni fattori di rischio per le malattie cronico-degenerative, in gruppi di popolazione “a rischio”. La prima parte della tesi (approccio in vivo) ha avuto l’obiettivo di valutare l’impatto di due diversi interventi dietetici in una popolazione di bambini ed adolescenti italiani affetti da iperlipidemia primaria, e quindi considerati a maggior rischio di possibili eventi cardiovascolari futuri. In primo luogo, la popolazione pediatrica in studio è stata caratterizzata per il profilo lipidico sierico e per la composizione degli acidi grassi dei fosfolipidi delle membrane eritrocitarie, mostrando delle differenze in base al sesso e al tipo specifico di iperlipidemia. Inoltre, in questi soggetti è stata osservato un basso indice omega 3 (acido eicosapentaenoico, EPA + acido docosaesaenoico, DHA: <4%), un marker che è stato suggerito essere associato a un elevato rischio di sviluppare malattie cardiovascolari. In secondo luogo, nella stessa popolazione di pazienti pediatrici iperlipidemici è stato studiato l’effetto del consumo regolare di uno specifico alimento (nocciole, HZN) o un supplemento alimentare (olio di semi di canapa, HSO), entrambi ricchi in acidi grassi insaturi e altri bioattivi, nella modulazione di diversi biomarker di rischio cardiovascolare collegati all’iperlipidemia. Entrambi gli interventi dietetici sono risultati efficaci nella gestione dell’iperlipidemia pediatrica. In particolare, abbiamo dimostrato che l’assunzione per 8 settimane di nocciole, consumate con la cuticola (HZN+S) oppure pelate (HZN-S), migliorava significativamente il profilo lipidico sierico e aveva un impatto favorevole anche sulla composizione degli acidi grassi delle membrane eritrocitarie. Inoltre, i trattamenti dietetici con le nocciole sono stati in grado di ridurre i livelli di danno al DNA, un marker di stress ossidativo. Tuttavia, le concentazioni plasmatiche di LDL ossidate (ox-LDL) non hanno subito alcun cambiamento in seguito all’intervento con le nocciole. L’effetto della supplementazione con olio di semi di canapa nella modulazione del profilo lipidico in bambini iperlipidemici è stato valutato attraverso uno studio pilota. Anche se preliminari, i risultati di questo studio hanno mostrato un miglioramento dell’indice omega 3 e della composizione degli acidi grassi delle membrane eritrocitarie in seguito all’assunzione dell’olio di semi di canapa per 8 settimane. La seconda parte della tesi di dottorato è stata svolta su modelli ex vivo presso il Dipartimento di Fisiologia e Biochimica della Nutrizione del Max Rubner-Institut (Karlsruhe, Germania). Considerando che le malattie cronico-degenerative sono spesso associate ad una risposta immunitaria compromessa, l’obiettivo di questa parte di ricerca è stato quello di studiare il potenziale effetto immunomodulatorio di diverse concentrazioni di acidi grassi polinsaturi a lunga catena (LC-PUFA), in combinazione con dosi standard di vitamina D3, in cellule immunitarie ex vivo prelevate da volontari sani. L’effetto di questi composti bioattivi è stato valutato su due meccanismi implicati nella risposta immunitaria innata, che agiscono specificatamente contro le cellule tumorali e gli agenti patogeni: l’attivita delle cellule natural killer (NK) e la fagocitosi. I risultati ottenuti hanno mostrato che gli LC-PUFA ad elevate dosi, indipendentemente dalla presenza o meno della vitamina D, interferiscono negativamente sulla capacità delle cellule NK di lisare e contrastare le cellule tumorali target, mostrando una risposta dose-dipendente. Al contrario, è stato osservato un miglioramento dell’attività fagocitaria dei monociti quando gli LC-PUFA erano coincubati con la vitamina D, suggerendo un potenziale effetto sinergico e immunomodulatorio della vitamina D. In conclusione, attraverso questa tesi di dottorato è stato possibile aumentare le conoscenze sul potenziale effetto di diete ricche in composti bioattivi nella modulazione di alcuni fattori di rischio per le malattie cronico-degenerative. Questo aspetto risulta particolarmente importante soprattutto nelle popolazioni target considerate più a rischio e per le quali un intervento nutrizionale appropriato e personalizzato viene considerato l’approccio di prevenzione primario. Studi futuri su gruppi di popolazione più ampi e volti a valutare i meccanismi d’azione specifici sono necessari al fine di fornire delle dimostrazioni aggiuntive che confermino i nostri risultati.The rapid increase in prevalence of chronic-degenerative diseases is probably the major global health problem nowadays. Several studies have emphasized the role that dietary patterns rich in specific foods or their bioactive compounds may play in the reduction of disease risk. In fact, nutritional intervention is considered one of the most significant, easily achieved and affordable primary prevention strategy. Recently, increasing interest has been focused on personalized dietary interventions accurately designed to meet specific nutritional needs of target groups of population. The personalized approach seems to be more effective to achieve a defined outcome, especially in targeted subgroups of population considered “at higher risk” to develop chronic diseases. Based on these premises, the aim of the present Ph.D. thesis was to evaluate the effect of specific foods and their bioactives in the modulation of risk factors for chronic-degenerative diseases in “at risk” groups of population, thorough both in vivo and ex vivo approaches. The first part (in vivo approach) was focused on the impact of two different dietary interventions in a population of Italian children and adolescents affected by primary hyperlipidemia and thus considered at “higher risk” to develop cardiovascular (CV) events later in life. Firstly, the study population was characterized for serum lipid profile and fatty acid (FA) composition of red blood cell (RBC) phospholipids, showing differences according to sex and diagnosis of hyperlipidemia. Moreover, in the hyperlipidemic pediatric patients we observed an overall low omega 3 index (eicosapentaenoic acid, EPA + docosahexaenoic acid, DHA: <4%), an emerging risk factor for cardiovascular diseases (CVD). Secondly, in the same population of hyperlipidemic pediatric patients, it was investigated the effect of regular intake of a specific food (hazelnuts, HZN) or food supplement (hempseed oil, HSO) rich in unsaturated fats and other bioactives, in the modulation of different CVD biomarkers related to hyperlipidemia. We documented that both dietary treatments were effective in the management of primary hyperlipidemia at pediatric age. In particular, we showed that 8-week of hazelnuts intake, consumed with skin (HZN+S) or without skin (peeled, HZN-S), significantly improve the serum lipid profile and had a favorable impact on FAs composition of RBC membranes. In addition, HZN treatments were able to reduce the levels of DNA damage, a marker of oxidative stress, even if the concentrations of plasma oxidized LDL (ox-LDL) did not change following the HZN intervention. The effect of HSO supplementation on lipid profile of hyperlipidemic children was evaluated through a pilot study. Even if preliminary, the results from this study showed an enhancement of the omega-3 index and the RBC phospholipid composition following the intake of HSO for 8 weeks. The second part of the Ph.D thesis was performed at the Department of Physiology and Biochemistry of Nutrition of Max Rubner-Institut (Karlsruhe, Germany) and devoted to ex vivo approaches. Considering that chronic diseases are often associated to a compromised immune response, the objective of this part of research was to investigate the potential immunomodulatory properties of different concentrations of long-chain polyunsaturated fatty acids (LC-PUFA) in conjunction with standard dose of vitamin D3 on ex vivo immune cells from healthy volunteers. The effect of these bioactives was evaluated on two mechanisms crucially involved in the innate immune response that specifically act against cancer cells as well as infectious agents: the natural killer (NK) cell activity and the phagocytosis. The findings showed that high dose of LC-PUFA, independently by the presence of the vitamin D, negatively affect the lytic activity of NK cell of target cancer cells, with a dose-dependent response. On the contrary, an enhancement of phagocytic activity of monocytes was observed only when LC-PUFA were combined with vitamin D, suggesting a potential synergic and immunomodulatory role of vitamin D. In conclusion, through this Ph.D thesis it was possible to increase knowledge on the potential benefits of bioactives rich-diet in the modulation of different risk factors for chronic-degenerative diseases. This aspect is particulary important in at risk target groups of population for whom appropriate and personalized nutritional interventions are considered the primary prevention approach. Future studies on largest population groups aimed to clarify the specific mechanisms of action involved are needed to provide additional demonstration that confirm our results

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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