Cross-species infectivity of H3N8 influenza virus in an experimental infection in swine

Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool.We thank Jaime Maldonado and HIPRA (Spain) for the A/Swine/Spain/ 54008/2004 (H3N2) strain, Edward J. Dubovi and Cornell University for the A/Canine/NY/105447/08 (H3N8) IAV strain, T. M. Chambers and the University of Kentucky for the A/Equine/OH/1/03 (H3N8) IAV strain, and Hon Ip and the U.S. Geological Survey National Wildlife Health Center for the A/American black duck/Maine/44411-532/2008 (H3N8) and the A/Harbor Seal/New Hampshire/179629/2011 (H3N8) IAV strains. We thank Sergio López, David Solanes, Francisco X. Abad, Jordi Alberola, Jaume Martorell, and Eduard J. Cunilleras for help in providing different samples and during the experimental infections, as well as the personnel in Cat3 laboratories and the animal house. We thank Adolfo García-Sastre for providing materials and for support as the principal investigator of the NIAID-funded Center for Research in Influenza Pathogenesis (HHSN266200700010C). The research leading to these results received funding from the European Community’s Seventh Framework Programme (FP7, 2007-2013), the Research Infrastructures Action under grant FP7-228393 (a NADIR project), and projects AGL2010-22200-C02-01 and AGL2007-60274 of the Spanish Ministry of Science and Innovation

Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; Potential marker of disease recurrence

Background: Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods. A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry. Results: Higher levels of methylation were associated with disease recurrence. In particular, MLH1, ATM and FHIT gene promoters were found to be significantly hypermethylated in recurring adenomas. Unconditional logistic regression analysis used to evaluate the relative risk (RR) of recurrence showed that FHIT and MLH1 were independent variables with an RR of 35.30 (95% CI 4.15-300.06, P = 0.001) and 17.68 (95% CI 1.91-163.54, P = 0.011), respectively. Conclusions: Histopathological classification does not permit an accurate evaluation of the risk of recurrence of colorectal lesions. Conversely, results from our methylation analysis suggest that a classification based on molecular parameters could help to define the mechanisms involved in carcinogenesis and prove an effective method for identifying patients at high risk of recurrence

Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy

<p>Abstract</p> <p>Background</p> <p>Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer.</p> <p>Methods</p> <p>Fresh surgical biopsy specimens were obtained from 30 patients with primary or recurrent peritoneal carcinomatosis from ovarian cancer. <it>ERCC1, GSTP1, MGMT, XPD</it>, and <it>BRCA1 </it>gene expression levels were determined by Real-Time RT-PCR. An <it>in vitro </it>chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.</p> <p>Results</p> <p><it>MGMT </it>and <it>XPD </it>expression was directly and significantly related to resistance to platinum-containing treatment (p = 0.036 and p = 0.043, respectively). Significant predictivity in terms of sensitivity and resistance was observed for <it>MGMT </it>expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity of resistance (90.9%) but very low predictivity of sensitivity (37.5%) (p = 0.06) were observed for <it>XPD</it>. The best overall and significant predictivity was observed for chemosensitivity test results (85.7% sensitivity and 91.3% resistance; p = 0.0003).</p> <p>Conclusions</p> <p>The in vitro assay showed a consistency with results observed in vivo in 27 out of the 30 patients analyzed. Sensitivity and resistance profiles of different drugs used in vivo would therefore seem to be better defined by the in vitro chemosensitivity test than by expression levels of markers.</p

Serum angiogenesis associated proteins and clinical outcome in metastatic colorectal cancer patients receiving bevacizumab

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MMR vaccine in the postpartum does not expose seronegative women to untoward effects.

Contesto : Lo scopo di questo studio è stato quello di valutare se la vaccinazione rosolia immediatamente dopo il parto potrebbe esporre le donne sieronegative per effetti indesiderati specifici.Metodi : 163 donne rosolia-sieronegativi hanno ricevuto il vaccino MMR nel periodo post-partum; sono stati valutati a 1 mese a 3 mesi successivi attraverso interviste telefoniche. Come controlli, abbiamo confrontato 163 donne rosolia-sieropositivi, che potrebbe avere sintomi simili per qualsiasi motivo, nello stesso arco di tempo.Risultati : A un mese di follow-up, 161 donne nel gruppo dei casi e 162 controlli hanno risposto alla nostra intervista telefonica; alle tre mesi di follow-up, 154 casi e 159 controlli. Eruzione cutanea, faringite, artralgia, linfoadenopatia cervicale, mialgia e parestesia sono state le lamentele più frequentemente riportati in entrambi i gruppi. Una differenza statisticamente significativa nella frequenza di linfoadenopatia cervicale e rash cutaneo a un mese (p = 0.028 ep = 0.005, rispettivamente) è stata osservata tra i casi ei controlli; Tuttavia, nessuna differenza significativa è stata ancora osservata nella frequenza delle manifestazioni muscoloscheletriche acute e croniche a tre mesi.Conclusioni : Non sono sostanziali differenze sono stati segnalati tra casi e controlli per quanto riguarda la frequenza di artralgia e conseguente mialgia al MMR vaccinazione in post-partum . Postpartum rosolia la vaccinazione è sicura e consigliabile in caso di necessità per evitare la circolazione del virus e la sindrome da rosolia congenita

Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies.</p> <p>Methods</p> <p>Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade.</p> <p>Results</p> <p>Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions.</p> <p>Conclusions</p> <p>This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.</p> <p>The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].</p

Tra genere e generi. Tradurre e pubblicare testi per ragazze e ragazzi

Il volume nasce nell'ambito di un progetto AlmaIdea sulla traduzione di testi per l'infanzia in una prospettiva di genere, e propone una serie di contributi interdisciplinari, al crocevia fra studi traduttologici, letterari e di genere, focalizzati su svariate tipologie di testi per l'infanzia, letterari e non, tradotti dal francese, dall'inglese e dallo spagnolo, un ambito di ricerca ad oggi poco approfondito a livello internazionale e ancor più nel contesto accademico italiano. Nel testo viene proposto, infine, un documento ispirato al Codice Polite e volto a fornire alle case editrici così come a traduttrici e traduttori alcuni suggerimenti al fine di tradurre e pubblicare testi in una prospettiva di inclusione e sensibilità per gli aspetti di genere e delle diversità tutte