1,720,959 research outputs found

    Ipossia ed infiammazione nella progressione del carcinoma vescicale

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    Dimostrare che il microambiente del tumore della vescica, nel corso della fase iniziale di crescita diventa ipossico, attivando l’asse HIF/NFkB e mediante i geni così trascritti, è responsabile della progressione maligna. Mediante la microdissezione dei campioni chirurgici ed estrazione degli acidi nucleici e proteine dalle frazioni omogenee (cellule di tessuto tumorale e cellule di tessuto ospite) si è proceduto all’analisi molecolare tramite card microfluide customizzate con geni HIF e NFkB dipendenti ed analisi delle proteine in Western Blot per confermare i livelli di espressione dei geni rilevati (sia nel tessuto ospite che nel tumorale) responsabili dell’acquisizione delle proprietà della malignità. Conferma dell'attivazione e della sovraespressione dei geni dipendenti da HIF-1: geni per la neoangiogenesi VEGFs; geni per i recettori delle allarmine RAGE/P2X7; geni proinfiammatori CXCR4; geni per l’invasione tumorale MMP9/SOCS-1; geni per la riparazione del danno tissutale EGFR. Confermata l’attivazione e la sovraespressione di NFkB e dei geni dipendenti: geni proinfiammatori COX2/NOS2; proteine di fase acuta PTX3, etc. È stato studiato l’effetto dell’ipossia sulle cellule staminali isolate dal carcinoma vescicale uroteliale con lo scopo di verificare che le sovraespressioni geniche indotte dall’ipossia siano presenti anche in esse. Le cellule staminali tumorali rispondono ai vari modificatori biologici e svolgono un ruolo fondamentale nella formazione delle metastasi. Tali cellule sono state incubate in condizioni di ipossia per 60 minuti. L’analisi trascrittomica ottenuta utilizzando la nostra inflammocard (contenente un totale di 48 geni rappresentativi dell’espressione dipendente dall’asse HIF/NFkB) rivela un’aumentata espressione genica di tutti i geni HIF/NFkB-dipendenti rispetto alle condizioni normossiche in varia maniera associati alle caratteristiche della malignità. È stato eseguito un Western Blot sia sui campioni vescicali tumorali che su quelli ospite del tumore per escludere la presenza di infiltrati leucocitari (cellule CD45+). L’analisi dell’espressione proinfiammatoria delle cellule tumorali indotta dall’attivazione dell’asse HIF/NFkB si presenta simile ad una risposta Th1 o risposta cellulo-mediata. Le cellule tumorali producono soprattutto citochine Th1, rispondono con la migrazione alle chemochine e ai fattori chemiotattici per linfociti, NK e macrofagi e producono mediatori con la stessa cinetica della risposta Th1. Inoltre, nel tessuto tumorale richiamano soprattutto linfociti, macrofagi, NK e cellule dendritiche. La risposta migratoria del tumore primitivo all’homing per la metastasi è prevalentemente legata a stimoli periferici di tipo Th1. Infine, la definizione del ruolo dell’asse HIF/NFkB nella progressione maligna, suggerisce che un array a bassa densità (contenente 48-96 geni opportunamente selezionati tra le varie famiglie geniche dimostrate coinvolte nell’acquisizione delle caratteristiche della malignità) può definire la progressione di un tumore della vescica e, pertanto, dare una base molecolare e meccanicistica alla stadiazione di un tumore, indipendentemente dal grado istologico

    Role of percutaneous tibial nerve stimulation in the treatment of neurogenic overactive bladder syndrome

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    Aim: Overactive Bladder Syndrome (OAB) is characterized by a series of urinary symptoms such as incontinence, urgency, frequency, nocturia and it is nowadays differentiated in OAB due to an involuntary urodynamic detrusor contraction responsible of the symptoms and Neurogenic Detrusor Overactivity (NDO). Most of the neurologic pathologies can be responsible of NDO such as Parkinson disease, multiple sclerosis, spinal cord injury, cerebral palsy, brain tumors, cerebrovascular pathologies and meningomyelocele and the lower urinary tract dysfunction depend on the site and the completeness of the associated neurological lesions. Aim of the study is to evaluate preliminary results on symptoms and urodynamic findings of posterior tibial nerve stimulation (PTNS) in patients with NDO. Methods: Twelve patients (pts), 9 men and 3 females, age ranged from 25 and 76 years with clinical and urodynamic diagnosis of NDO were included in the study. Electrical stimulations were applied unilaterally from the medial malleolus and posterior to the edge of the tibia twice a week for a total of 6 weeks. Urodynamic parameters were evaluated before and after treatment. Overactive bladder questionnaire (AOB-q) and voiding diary were performed in all pts before treatment after 6 electrical stimulations and at the end of treatment. Results: PTNS was found to be effective on OAB symptoms in all pts according to the data of the questionnaires and voiding diary. Mean 1st involuntary detrusor contraction (IDC) and mean maximum cistometric capacity (MCC) were significantly improved on standard cystometry. 8 pts (66.6%) showed a complete disappearance of IDC and the other 4 pts (33.3%) showed an increased filling volume to IDC. No complications have been reported and pts compliance to treatment was very high. Conclusions: PTNS is an effective and safe option to treat pts with symptoms from NDO. Further studies are needed to assess the role of this technique and to establish the length of treatment in order to maintain the results obtaine

    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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    The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression

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    The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from the initiation to the malignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a "physiological" response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progressi
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