The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development

Funding Information: This work was supported by the Italian Ministry of Health Ricerca Corrente 2022 Grant L1/10. M.I. Isaguliants was supported by the Latvian Science Fund, project LZP 2021/1-0484. Publisher Copyright: © 2022 by the authors.Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein–Barr virus (EBV) LMP1, Kaposi’s sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate on recent findings on virus–telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer-causing viruses.publishersversionPeer reviewe

Age above 70 years and Charlson Comorbidity Index higher than 3 are associated with reduced survival probabilities after radical cystectomy for bladder cancer. Data from a contemporary series of 334 consecutive patients.

Objective: To assess the joint effect of age and comorbidities on clinical outcomes of radical cystectomy (RC).Methods: 334 consecutive patients undergoing open RC for bladder cancer (BC) during the years 2005-2015 were analyzed. Pre-, peri- and post-operative parameters, including age at RC (ARC) and Charlson Comorbidity Index (CCI), were evaluated. Overall and cancer-specific survivals (OS, CSS) were assessed by univariate and multivariate modelling. Furthermore, a three-knot restricted cubic spline (RCS) was fitted to survival data to detect dependency between death-rate ratio (HR) and ARC. Results: Median follow-up time was 3.8 years (IQR = 1.3-7.5) while median OS was 5.9 years (95%CL = 3.8-9.1). Globally, 180 patients died in our cohort (53.8%), 112 of which (62.2%) from BC and 68 patients (37.8%) for unrelated causes. After adjusting for preoperative, pathological and perioperative parameters, patients with CCI > 3 showed significantly higher death rates (HR = 1.61; p = 0.022). The highest death rate was recorded in ARC = 71-76 years (HR = 2.25; p = 0.034). After fitting an RCS to both OS and CSS rates, two overlapping nonlinear trends, with common highest risk values included in ARC = 70-75 years, were observed. Conclusions: Age over 70 years and CCI > 3 were significant factors limiting the survival of RC and should both be considered when comparing current RC outcomes

Image-Guided Intraoperative Assessment of Surgical Margins in Oral Cavity Squamous Cell Cancer: A Diagnostic Test Accuracy Review

(1) Background: The assessment of resection margins during surgery of oral cavity squamous cell cancer (OCSCC) dramatically impacts the prognosis of the patient as well as the need for adjuvant treatment in the future. Currently there is an unmet need to improve OCSCC surgical margins which appear to be involved in around 45% cases. Intraoperative imaging techniques, magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS), have emerged as promising tools in guiding surgical resection, although the number of studies available on this subject is still low. The aim of this diagnostic test accuracy (DTA) review is to investigate the accuracy of intraoperative imaging in the assessment of OCSCC margins. (2) Methods: By using the Cochrane-supported platform Review Manager version 5.4, a systematic search was performed on the online databases MEDLINE-EMBASE-CENTRAL using the keywords "oral cavity cancer, squamous cell carcinoma, tongue cancer, surgical margins, magnetic resonance imaging, intraoperative, intra-oral ultrasound". (3) Results: Ten papers were identified for full-text analysis. The negative predictive value (cutoff < 5 mm) for ioUS ranged from 0.55 to 0.91, that of MRI ranged from 0.5 to 0.91; accuracy analysis performed on four selected studies showed a sensitivity ranging from 0.07 to 0.75 and specificity ranging from 0.81 to 1. Image guidance allowed for a mean improvement in free margin resection of 35%. (4) Conclusions: IoUS shows comparable accuracy to that of ex vivo MRI for the assessment of close and involved surgical margins, and should be preferred as the more affordable and reproducible technique. Both techniques showed higher diagnostic yield if applied to early OCSCC (T1-T2 stages), and when histology is favorable

Fatigue as hallmark of Fabry disease: role of bioenergetic alterations

Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of the α-galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan dysfunction. Exercise intolerance and fatigue are frequent and early findings in FD patients, representing a self-standing clinical phenotype with a significant impact on the patient's quality of life. Several determinants can trigger fatigability in Fabry patients, including psychological factors, cardiopulmonary dysfunctions, and primary alterations of skeletal muscle. The “metabolic hypothesis” to explain skeletal muscle symptoms and fatigability in Fabry patients is growing acknowledged. In this report, we will focus on the primary alterations of the motor system emphasizing the role of skeletal muscle metabolic disarrangement in determining the altered exercise tolerance in Fabry patients. We will discuss the most recent findings about the metabolic profile associated with Fabry disease offering new insights for diagnosis, management, and therapy

Patients' perceptions of quality of care delivery by urology residents: A nationwide study

Objective To present the results of a nationwide survey among urological patients to evaluate their perception of the quality of care provided by residents. Methods An anonymous survey was distributed to patients who were referred to 22 Italian academic institutions. The survey aimed to investigate the professional figure of the urology resident as perceived by the patient. Results A total of 2587 patients were enrolled in this study. In all, 51.6% of patients were able to correctly identify a urology resident; however, almost 40% of respondents discriminated residents from fully trained urologists based exclusively on their young age. Overall, 98.2% patients rated the service provided by the resident as at least sufficient. Urology trainees were considered by more than 50% of the patients interviewed to have good communication skills, expertise and willingness. Overall, patients showed an excellent willingness to be managed by urology residents. The percentage of patients not available for this purpose showed an increasing trend that directly correlated with the difficulty of the procedure. Approximately 5-10% of patients were not willing to be managed by residents for simple procedures such as clinical visits, cystoscopy or sonography, and up to a third of patients were not prepared to undergo any surgical procedure performed by residents during steps in major surgery, even if the residents were adequately tutored. Conclusions Our data showed that patients have a good willingness to be managed by residents during their training, especially for medium- to low-difficulty procedures. Furthermore, the majority of patients interviewed rated the residents' care delivery as sufficient. Urology trainees were considered to have good communication skills, expertise and willingness

Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction). Fatigue and exercise intolerance are early common symptoms in FD patients but the specific causes are still to be defined. In this narrative review, we deal with the contribution of cardiac and pulmonary dysfunctions in determining fatigue and exercise intolerance in FD patients

La geografia finanziaria delle terre rare

Le terre rare comprendono diciassette elementi e si stima siano ampiamente diffusi in tutto il globo. Tuttavia, la loro estrazione risulta essere particolarmente difficile e sono strategicamente importanti per molte produ zioni. La ricerca tenta di individuare degli schemi geografici legati al commercio delle terre rare evidenziandone tendenze e prospettive. Attraverso un’analisi dettagliata, quindi, la ricerca vuole tratteggiare un quadro delle attività finanziarie connesse alle terre rare. In questo modo, si cercherà di descrivere una parte importante di quel mondo digitale che rive stirà sempre maggiore importanza negli anni a venire

Qualified Migrations: the Italian Case / Migracje pracowników wykwalifikowanych: sytuacja we Włoszec

This article investigates the phenomenon of migrations of highly qualified workers with particular reference to the Italian case. In the course of the article we will move from the examination of the traditional literature on the subject of qualified migrations, taking into account the most recent research on the European situation, until narrowing the attention to the Italian situation. The Italian scenario presents a series of peculiarities that the article will show off. Firstly, it will be underlined that in recent years considerable flows of mi- grants have started to leave Italy, directed above all towards the countries of the European Union: the range of these new migrations can be compared to the number of people who left the country during the Fifties. Secondly, it will be highlight- ed that the new flows of migrants leaving Italy are very different from those of the past: a high percentage of those who leave have a high level of education or already have a specialization in work. Within this section there is also a brief analysis of the qualified migrations within Italy: the results highlight how the young qualified workers – or students – of the South are pushed more and more to leave their regions of origin to head towards the Northern regions, historically richer and more dynamic. Therefore, it is emphasized that in Italy there is an internal brain drain that causes an intellectual depletion of the Southern regions: it will be also noted that the young qualified natives of Northern Italy, instead, emigrate mainly to other European countries such as, for example, Germany and Great Britain. The results of the research tend to in- dicate that Italy is for now a net export- er of highly skilled workers given that skilled foreign workers who choose Italy as a workplace are a very small proportion of the immigrants who annually reach the country. However, the situation tends to improve if the situation of foreigners en- rolling in degree courses at Italian universities is taken into consideration: the data presented in the article show that without the contribution of foreign members the decline in enrolment at Italian universities would have been much more considerable