Alternative splicing of the human gene SYBL1 modulates protein domain architecture of longin VAMP7/TI-VAMP, showing both non-SNARE and synaptobrevin-like isoforms

<p>Abstract</p> <p>Background</p> <p>The control of intracellular vesicle trafficking is an ideal target to weigh the role of alternative splicing in shaping genomes to make cells. Alternative splicing has been reported for several Soluble <it>N</it>-ethylmaleimide-sensitive factor Attachment protein REceptors of the vesicle (v-SNAREs) or of the target membrane (t-SNARES), which are crucial to intracellular membrane fusion and protein and lipid traffic in Eukaryotes. However, splicing has not yet been investigated in Longins, i.e. the most widespread v-SNAREs. Longins are essential in Eukaryotes and prototyped by VAMP7, Sec22b and Ykt6, sharing a conserved N-terminal Longin domain which regulates membrane fusion and subcellular targeting. Human VAMP7/TI-VAMP, encoded by gene SYBL1, is involved in multiple cell pathways, including control of neurite outgrowth.</p> <p>Results</p> <p>Alternative splicing of SYBL1 by exon skipping events results in the production of a number of VAMP7 isoforms. In-frame or frameshift coding sequence modifications modulate domain architecture of VAMP7 isoforms, which can lack whole domains or domain fragments and show variant or extra domains. Intriguingly, two main types of VAMP7 isoforms either share the inhibitory Longin domain and lack the fusion-promoting SNARE motif, or vice versa. Expression analysis in different tissues and cell lines, quantitative real time RT-PCR and confocal microscopy analysis of fluorescent protein-tagged isoforms demonstrate that VAMP7 variants have different tissue specificities and subcellular localizations. Moreover, design and use of isoform-specific antibodies provided preliminary evidence for the existence of splice variants at the protein level.</p> <p>Conclusions</p> <p>Previous evidence on VAMP7 suggests inhibitory functions for the Longin domain and fusion/growth promoting activity for the Δ-longin molecule. Thus, non-SNARE isoforms with Longin domain and non-longin SNARE isoforms might have somehow opposite regulatory functions. When considering splice variants as "natural mutants", evidence on modulation of subcellular localization by variation in domain combination can shed further light on targeting determinants. Although further work will be needed to characterize identified variants, our data might open the route to unravel novel molecular partners and mechanisms, accounting for the multiplicity of functions carried out by the different members of the Longin proteins family.</p

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p&lt;0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p&lt;0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p&lt;0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p&lt;0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

Anais do V Encontro Brasileiro de Educomunicação: Educação midiática e políticas públicas

A presente coletânea, que chega ao público através de um suporte digital, tem como objetivo disponibilizar os papers, bem como os relatos de experiências educomunicativas apresentados durante o V ENCONTRO BRASILEIRO DE EDUCOMUNICAÇÃO, que teve como tema central: “Educação Midiática e Políticas Públicas”. O evento foi realizado em São Paulo, entre 19 e 21 de setembro de 2013, a partir de uma parceria entre o NCE/USP - Núcleo de Comunicação e Educação da USP, a Licenciatura em Educomunicação da ECA/USP, a ABPEducom – Associação Brasileira de Pesquisadores e Profissionais da Educomunicação e a FAPCOM – Faculdade Paulus de Tecnologia e Comunicação, que ofereceu seu campus, na Vila Mariana, para os atos do evento. Os presentes anais disponibilizam o texto de abertura, de autoria do coordenador geral do evento, denominado “Educação midiática e políticas públicas: vertentes históricas da emergência da Educomunicação na América Latina”. Na sequência, apresentam 61 papers sobre aspectos específicos da temática geral, resultantes de pesquisas na área, seguidos de 27 relatos de práticas educomunicativas, em nível nacional

Management delle cisti ovariche in menopausa

Il trattamento di una cisti ovarica dipende dalla sua natura, per cui un’accurata diagnosi differenziale tra patologia maligna e benigna è di cruciale importanza, specialmente dopo la menopausa poichè aumenta il rischio di cancro ovarico. La discriminazione preoperatoria di una cisti ovarica è una sfida avvincente. Dalla review della letteratura da noi effettuata concernente la diagnosi ed il trattamento delle cisti ovariche dopo la menopausa, si può osservare come siano stati discussi diversi criteri discriminativi quali l’età, lo status post-menopausale, la morfologia ecografica, l’eco colorDoppler, l’indice di rischio di malignità (RMI). In generale è raccomandabile un atteggiamento di attesa in donne con cisti non sospette, uniloculate, anecogene con livelli normali di CA-125. L’intervento chirurgico è invece raccomandato in cisti di diametro superiore ai 5 cm e/o con livelli elevati di CA-125. In donne sintomatiche, inoltre, l’indicazione alla chirurgia è assoluta. L’utilizzo combinato di più metodiche incrementa la possibilità di fare una diagnosi corretta. Purtroppo, però, siamo ancora ben lontani dal raggiungere una metodica che ci permetta con una adeguata sensibilità e specificità di poter porre una diagnosi certa. I primi risultati su studi di proteomica sul siero sembrano promettenti, e si spera che, in combinazione con altre metodiche diagnostiche, si possa giungere ad un approccio diagnostico multimodale nella diagnosi di carcinoma ovarico. Si auspica in tal maniera di migliorare la capacità di discriminare tra cisti benigne e maligne in modo tale da evitare un intervento chirurgico non necessario

Management clinico della gravidanza post-termine

Secondo la definizione internazionale approvata dalla World Health Organization (WHO) e dall’International Federation of Gynecology and Obstetrics (FIGO), con il termine di gravidanza post-termine viene indicata una gravidanza che si protrae per un tempo maggiore o uguale a 42 settimane di amenorrea (oppure 294 giorni di amenorrea). Senza nessun intervento ostetrico si stima che approssimativamente il 10% (range 3-14%) di tutte le gravidanze continui oltre le 42 settimane, ed il 4% oltre le 43 settimane complete. L’eziologia di tale condizione clinica è sconosciuta anche se sono state individuate specifiche condizioni predisponenti. Il meccanismo patogenetico è da ricondurre probabilmente ad anomalie dei fattori in causa nell’iniziare il travaglio di parto. Il management delle gravidanze post-termine è estremamente controverso: vanno considerati l’età gestazionale, i risultati dei test antenatali fetali, le condizioni del collo uterino, oltre alle preferenze espresse dalla madre dopo esauriente spiegazione dei rischi e benefici connessi alle alternative possibili, costituite dall’induzione contro l’attesa con monitoraggio. Attualmente la maggior parte dei ginecologi induce il travaglio tra la 41ª e la 42ª settimana, e quasi tutti non permettono che la gravidanza perduri oltre la 43ª settimana di gestazione