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    La sorveglianza del morbillo per la Regione Liguria negli ultimi cinque anni.

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    Introduzione: Il virus del morbillo appartiene al genere Morbillivirus della famiglia dei Paramixoviridae. Il virione contiene un RNA non–segmentato, a singolo strand, di senso negativo di circa 16 kb. Il genoma contiene 6 geni che codificano per 6 proteine: proteina del nucleocapside (N), fosfoproteina (P), proteina della matrice (M), proteina di fusione (F), emoagglutinina (H) e proteina grande (L). Il virus del morbillo è nato come una zoonosi da quello della peste bovina (bovini peste). Ad oggi l'uomo è l'unico serbatoio naturale del virus. Il contagio avviene per via aerea, con il virus trasportato dalle goccioline di Flugge ovvero le micro gocce di saliva che vengono emesse attraverso il respirare lo starnutire o il tossire, e per contatto diretto o indiretto con i fluidi corporei di una persona malata (saliva, sperma, muco). Il virus penetra attraverso le mucose respiratorie e la congiuntiva e raggiunge i linfonodi dove si moltiplica e si diffonde così per via sistemica. L'incubazione dura circa 10 giorni. La viremia ha un picco in corrispondenza del 12° giorno dopo il contagio. E' una patologia particolarmente contagiosa per cui rientra tra le patologie da notifica obbligatoria. E' disponibile un vaccino. Il PNPV 2017-2019 prevede il Vaccino anti Morbillo-Parotite-Rosolia. Il sistema di sorveglianza WHO si pone l’obiettivo di eliminare la trasmissione endemica mantenendo alti i livelli delle vaccinazioni e implementando il sistema di sorveglianza in particolar modo nell’ambito del WHO Global Measles and Rubella laboratory Network . A livello nazionale è stata istituita una rete di laboratori afferenti alla rete MoRoNet con obbligo di notifica all'Istituto Superiore di Sanità dei casi confermati positivi. Oggetto di questa tesi è la descrizione dell'attività di sorveglianza per il morbillo della Regione Liguria negli ultimi cinque anni di lavoro. Materiali e metodi: Il laboratorio dell’UO Igiene dell’Ospedale Policlinico San Martino IRCCS, Università di Genova, raccoglie urine e tampone faringeo di pazienti con probabile o possibile morbillo, i casi da confermare e notificare su piattaforma MoRoNet quindi vengono analizzati come segue: estrazione degli acidi nucleici, amplificazione e sequenziamento del gene NP. Ottenuta la sequenza è possibile determinare il genotipo del virus circolante e confrontarlo con altre sequenze di riferimento disponibili o con altri casi di morbillo. Questa informazione si ottiene costruendo un albero filogenetico con programmi bioinformatici di allineamento di sequenze e analisi di omologia tra sequenze. Risultati: Nel laboratorio di riferimento della Regione Liguria nel periodo 2015-2019 abbiamo raccolto 114 casi di morbillo da confermare. Di questi 57 casi sono stati confermati positivi. La media dell'età sul periodo è risultata essere 26,8 anni e la mediana 32 anni. In particolare abbiamo riscontrato la presenza dei focolai epidemici nella provincia di Imperia tra la fine 2017 e l' 2018. I risultati dei test di caratterizzazione molecolare hanno permesso di identificare nei campioni raccolti nel 2018 un’unica variante di genotipo B3 circolante, mentre nel 2019 si è osservata la circolazione di diverse varianti appartenenti al genotipo D8 clade Manchester.UNK/3. Precedentemente le stagioni epidemiologiche sono state caratterizzate dalla circolazione della variante B3, quindi si conclude considerando attualmente una alternanza quasi annuale delle varianti circolanti di virus del morbillo. Conclusioni e discussione: Il morbillo continua a circolare in Italia e causare epidemie per le coperture vaccinali inadeguate nel corso degli anni, che hanno portato all’accumulo di ampie quote di popolazione suscettibili all’infezione. Le adesioni alla prima e alla seconda dose di vaccino MPR sono in aumento ma ancora inferiori al target del 95% e con una rilevante variabilità tra regioni. Inoltre l'elevata età mediana dei casi indica che esistono ampie sacche di giovani adulti suscettibili, mentre i casi tra gli operatori sanitari Imperiesi evidenziano il problema della bassa copertura vaccinale tra questi ultimi. E' infine evidente la necessità di individuare nel Piano nazionale per l'eliminazione del morbillo e della rosolia congenita nuove azioni rispetto a quanto previsto nei precedenti Piani, per esempio rafforzare la copertura nella popolazione adulta. Si conclude ricordando che l'obiettivo generale da raggiungere entro il 2023 è: incidenza <1 caso di morbillo / 1,000,000 popolazione, e tra gli obiettivi specifici rimane fondamentale raggiungere e mantenere una copertura vaccinale maggiore o uguale al 95% per la prima dose di morbillo.Introduction: Measles virus belongs to the genus Morbillivirus of the Paramixoviridae family. The virion contains a non-segmented RNA, a single strand, of a negative sense of approximately 16 kb. The genome contains 6 genes that code for 6 proteins: nucleocapsid protein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin (H) and large protein (L). Measles virus originated as a zoonosis from that of the bovine plague ( Rinderpest) . To date, man is the natural reservoir user of the virus. Contagion occurs by air, with the virus carried by the droplets of Flugge or the micro drops of saliva that are emitted through breathing, sneezing or coughing, and by direct or indirect contact with the body fluids of a sick person (saliva, sperm, mucus). The virus penetrates through the respiratory mucous membranes and the conjunctiva and observes the lymph nodes where it multiplies and spreads systemically. Incubation lasts approximately 10 days. The viraemia peaks in the correspondence on the 12th day after the infection. It is a particularly contagious pathology for which it falls under the pathologies of mandatory notification. A vaccine is available. The PNPV 2017-2019 provides for the measles-mumps-rubella vaccine.nThe WHO surveillance system aims to eliminate endemic transmission by keeping vaccination levels high and by implementing the surveillance system especially within the WHO Global Measles and Rubella laboratory Network. At national level, a network of laboratories has been set up belonging to the MoRoNet network with the obligation to notify the Istituto Superiore di Sanità of confirmed positive cases. The subject of this thesis is the description of the surveillance activity for measles of the Liguria Region in the last five years of work. Materials and methods: The laboratory of the Hygiene Unit of the Policlinico San Martino IRCCS Hospital, University of Genoa, collects urine and pharyngeal swab of patients with probable or possible measles, the cases to be confirmed and notified on the MoRoNet platform are therefore analyzed as follows: extraction of nucleic acids , amplification and sequencing of the NP gene. Once the sequence is obtained, it is possible to determine the genotype of the circulating virus and compare it with other available reference sequences or with other cases of measles. This information is obtained by building a phylogenetic tree with bioinformatic programs of sequence alignment and homology analysis between sequences. Results: In the reference laboratory of the Liguria Region in the period 2015-2019 we collected 114 cases of measles to be confirmed. Of these 57 cases were confirmed positive. The average age over the period was 26.8 years and the median 32 years. In particular, we found the presence of epidemic outbreaks in the province of Imperia between the end of 2017 and 2018. The results of the molecular characterization tests made it possible to identify a single circulating variant of genotype B3 in the samples collected in 2018, while in 2019 the circulation of several variants belonging to the D8 clade Manchester genotype was observed.UNK / 3. Previously the epidemiological seasons have been characterized by the circulation of the B3 variant, therefore it concludes considering at present an almost annual alternation of the circulating variants of measles virus. Conclusions and discussion: Measles continues to circulate in Italy and cause epidemics for inadequate vaccination coverage over the years, which have led to the accumulation of large portions of the population susceptible to infection. The adhesions to the first and second dose of MPR vaccine are increasing but still lower than the target of 95% and with a significant variability between regions. Furthermore, the high median age of the cases indicates that there are large pockets of susceptible young adults, while the cases among Imperia health workers highlight the problem of low vaccination coverage among the latter. Lastly, there is a clear need to identify new actions in the National Plan for the elimination of measles and congenital rubella compared to the previous Plans, for example to strengthen coverage in the adult population. It concludes by recalling that the general objective to be achieved by 2023 is: incidence <1 case of measles / 1,000,000 population, and among the specific objectives it remains essential to achieve and maintain a vaccination coverage greater than or equal to 95% for the first dose of measles

    IL-27 induces the expression of IDO and PD-L1 in human cancer cells

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    IL-27 is a member of the IL-12 family that is produced by macrophages and dendritic cells. IL-27 inhibits the growth and invasiveness of different cancers and therefore represents a potential anti-tumor agent. By contrast, it may exert immune-regulatory properties in different biological systems. We reported that IL-27 induces the expression of the IL-18 inhibitor IL-18BP, in human Epithelial Ovarian Cancer (EOC) cells, thus potentially limiting the immune response. Here, we tested whether IL-27 may modulate other immune-regulatory molecules involved in EOC progression, including Indoleamine 2,3-dioxygenase (IDO) and Programmed Death-Ligand (PD-L)1. IDO and PD-L1 were not constitutively expressed by EOC cells in vitro, but IL-27 increased their expression through STAT1 and STAT3 tyrosine phosphorylation. Differently, cells isolated from EOC ascites showed constitutive activation of STAT1 and STAT3 and IDO expression. These findings, together with the expression of IL-27 in scattered leukocytes in EOC ascites and tissues, suggest a potential role of IL-27 in immune-regulatory networks of EOC. In addition, IL-27 induced IDO or PD-L1 expression in monocytes and in human PC3 prostate and A549 lung cancer cells. A current paradigm in tumor immunology is that tumor cells may escape from immune control due to "adaptive resistance" mediated by T cell-secreted IFN-γ, which induces PD-L1 and IDO expression in tumor cells. Our present data indicate that also IL-27 has similar activities and suggest that the therapeutic use of IL-27 as anti-cancer agent may have dual effects, in some tumors

    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

    Different subcellular localization of ALCAM molecules in neuroblastoma: Association with relapse

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    Background: The Activated Leukocyte Cell Adhesion Mol. (ALCAM/CD166), involved in nervous system development, has been linked to tumor progression and metastasis in several tumors. No information is available on ALCAM expression in neuroblastoma, a childhood neoplasia originating from the sympathetic nervous system. Methods: ALCAM expression was analyzed by immunofluorescence and immunohistochem. on differentiated neuroblastoma cell lines and on archival specimens of stroma-poor, not MYCN amplified, resectable neuroblastoma tumors, resp. Results: ALCAM is variously expressed in neuroblastoma cell lines, is shed by metalloproteases and is cleaved by ADAM17/TACE in vitro. ALCAM is expressed in neuroblastoma primary tumors with diverse patterns of subcellular localization and is highly expressed in the neuropil area in a subgroup of cases. Tumor specimens showing high expression of ALCAM at the membrane of the neuroblast body or low levels in the neuropil area are assocd. with relapse (P=0.044 and P<0.0001, resp.). In vitro differentiated neuroblastoma cells show strong ALCAM expression on neurites, suggesting that ALCAM expression in the neuropil is related to a differentiated phenotype. Conclusion: Assessment of ALCAM localization by immunohistochem. may help to identify patients who, in the absence of neg. prognostic factors, are at risk of relapse and require a more careful follow-up
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