Investigating the impact of influenza on excess mortality in all ages in Italy during recent seasons (2013/14 - 2016/17 seasons)

Objectives: In recent years, Italy has been registering peaks in death rates, particularly among the elderly during the winter season. Influenza epidemics have been indicated as one of the potential determinants of such an excess. The objective of our study was to estimate the influenza-attributable contribution to excess mortality during the influenza seasons from 2013/14 to 2016/17 in Italy. Methods: We used the EuroMomo and the FluMomo methods to estimate the annual trend of influenza-attributable excess death rate by age group. Population data were provided by the National Institute of Statistics, data on influenza like illness and confirmed influenza cases were provided by the National Institutes of Health. As an indicator of weekly influenza activity (IA) we adopted the Goldstein index, which is the product of the percentage of patients seen with influenza-like illness (ILI) and percentage of influenza-positive specimens, in a given week. Results: We estimated excess deaths of 7,027, 20,259, 15,801 and 24,981 attributable to influenza epidemics in the 2013/14, 2014/15, 2015/16 and 2016/17, respectively, using the Goldstein index. The average annual mortality excess rate per 100,000 ranged from 11.6 to 41.2 with most of the influenza-associated deaths per year registered among the elderly. However children less than 5 years old also reported a relevant influenza attributable excess death rate in the 2014/15 and 2016/17 seasons (1.05/100,000 and 1.54/100,000 respectively). Conclusions: Over 68,000 deaths were attributable to influenza epidemics in the study period. The observed excess of deaths is not completely unexpected, given the high number of fragile very old subjects living in Italy. In conclusion, the unpredictability of the influenza virus continues to present a major challenge to health professionals and policy makers. Nonetheless, vaccination remains the most effective means for reducing the burden of influenza, and efforts to increase vaccine coverage and the introduction of new vaccine strategies (such as vaccinating healthy children) should be considered to reduce the influenza attributable excess mortality experienced in Italy and in Europe in the last seasons. Keywords: Flu, Mortality, Italy, Vaccinatio

Human Papilloma Virus (HPV) vaccination in Italy: towards new perspectives and new challenges

Human Papilloma virus (HPV) is the cause of a sexually transmitted infection which can lead to the development of genital warts, anogenital and oropharyngeal cancers. In Europe, about 90% of HPV-related cancers and 90% of genital warts are estimated to be vaccine preventable each year. In Italy, around 5,000 cases of cancers are due to HPV infections each year. This explains why HPV infection control is considered a public health priority

Strategies to achieve HPV-related disease control in Italy: results from an integrative approach

Background: achieving Human Papilloma Virus (HPV) - related diseases control is an important challenge in public health. In Italy HPV vaccination uptake does not rise a sufficient level. The aim of this project is to identify strategies to promote HPV vaccination in Italy.  Methods: an integrated approach consisting of a systematic review and a two-step panel consultation was used to identify strategies to increase vaccination uptake among adolescents, population target of the national vaccination program, and to promote vaccination in additional targets. Overall, ten experts in the fields of Gynecology, Public Health, General Practice and Pediatrics were involved along with Patients representatives. Recommendations were elaborated according to a set of criteria drawn from the Evidence to Decision (EtD) framework.  Results: the systematic review led to the identification of three categories of strategies: reminds, education and multicomponent approaches respectively. A strong recommendation was formulated to use reminds tailored to vaccine recipients or their parents, and a moderate recommendation to use reminds directed to health professionals. A moderate recommendation was developed on the implementation of multicomponent interventions. A strong recommendation was yielded with respect to the promotion of HPV vaccination among women already treated for HPV-related diseases, fertile women not previously vaccinated and 25 year-old women undergoing cervical cancer screening. Lastly, a strong recommendation was formulated for catch-up initiatives targeted to women and men turning 18 years of age.  Conclusion: this project led to the identification of several valuable strategies to improve HPV vaccination and strengthen HPV-related diseases control at national level.&nbsp

Survey of Professionals of the European Public Health Association (EUPHA) towards Direct-to-Consumer Genetic Testing

Background The increasing availability of Direct-to-Consumer Genetic Tests (DTC-GTs) has great implications for public health (PH) and requires literate healthcare professionals to address the challenges they pose. We designed and conducted a survey to assess the state of knowledge, attitudes and behaviours of PH professionals members of the European Public Health Association (EUPHA) towards DTC-GTs. Methods EUPHA members were invited to participate and fill in the survey. We performed multivariable logistic regression to evaluate associations between selected covariates and knowledge, attitudes and behaviours of healthcare professionals towards DTC-GT. Results Three hundred and two professionals completed the survey, 66.9% of whom were not involved in genetics or genomics within their professional activities. Although 74.5% of respondents were aware that DTC-GTs could be purchased on the web, most of them reported a low level of awareness towards DTC-GTs applications and regulatory aspects. The majority did not approve the provision of DTC-GTs without consultation of a healthcare professional (91.4%), were doubtful about the test utility and validity (61%) and did not feel prepared to address citizens' questions (65.6%). Predictors of knowledge on DTC-GT were the involvement in genetics/genomics and receiving training during the studies (P < 0.0001 and P = 0.043). Predictors of attitudes were medical degree and knowledge about DTC-GTs (P = 0.006 and P = 0.027). Conclusions Our results revealed a high level of awareness of DTC-GT web purchasing and a moderate to low level of awareness towards their applications. Despite the overall positive attitudes, PH professionals reported a high need for strengthening regulatory aspects of DTC-GTs provision process

Mitigating Errors on Superconducting Quantum Processors through Fuzzy Clustering

Quantum utility has been severely limited in superconducting quantum hardware until now by the modest number of qubits and the relatively high level of control and readout errors, due to the intentional coupling with the external environment required for manipulation and readout of the qubit states. Practical applications in the Noisy Intermediate Scale Quantum (NISQ) era rely on Quantum Error Mitigation (QEM) techniques, which are able to improve the accuracy of the expectation values of quantum observables by implementing classical post-processing analysis from an ensemble of repeated noisy quantum circuit runs. In this work, we focus on a recent QEM technique that uses Fuzzy C-Means (FCM) clustering to specifically identify measurement error patterns. For the first time, we report a proof-of-principle validation of the technique on a 2-qubit register, obtained as a subset of a real NISQ 5-qubit superconducting quantum processor based on transmon qubits. We demonstrate that the FCM-based QEM technique allows for reasonable improvement of the expectation values of single- and two-qubit gates based quantum circuits, without necessarily invoking state-of-the-art coherence, gate, and readout fidelities

Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review

BACKGROUND Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy. AIM To define if it is necessary reduce immunosuppression drugs during radiotherapy. METHODS The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND " and "OR " Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated. RESULTS The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type. CONCLUSION The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy

Stress in Medical Students: PRIMES, an Italian, Multicenter Cross-Sectional Study

Medical students (MSs) are healthcare workers and must also cope with education-related stressors. This study aims to assess factors associated with perceived stress in Italian MSs. A cross-sectional study was conducted in 12 Italian medical schools (MSCs) in November 2018. A questionnaire assessed socio-demographic characteristics, habits, opinions about MSC, and concerns about the future. Stress was assessed with the PSS-10. Descriptive and univariable tests were performed. A linear model was fitted to find associations of the PSS-10 score with characteristics. There were 2513 collected questionnaires. Median PSS-10 score was 18 (IQR 11). Median age was 22 (IQR 4) and 61% of the sample was female. Female gender, being part of a sexual minority, poor financial situation, competitive atmosphere, having hobbies, resting, and sleeping hindered by MSC were characteristics associated with higher PSS-10 scores. Current relationship, good family relationship, and no concerns about the future were protective factors. Being part of sexual minorities had greater effects in students not living away from home, while in the other group it was not having satisfying friendships. Medical students suffer higher levels of stress than the general population, and many MSC stressors are associated. Living away from home modifies risk and protective factors, offering the possibility to tailor group-specific interventions

Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation

Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells

Post-operative acute urinary retention after greenlight laser. Analysis of risk factors from a multicentric database

Purpose: Greenlight laser is a mini-invasive technique used to treat Benign Prostatic Obstruction (BPO). Some of the advantages of GreenLight photoselective vaporization (PVP) are shorter catheterization time and hospital stay compared to TURP. Post-operative acute urinary retention (pAUR) leads to patients' discomfort, prolonged hospital stay and increased health care costs. We analyzed risk factors for urinary retention after GreenLight laser PVP. Materials and methods: In a multicenter experience, we retrospectively analyzed the onset of early and late post-operative acute urinary retention in patients undergoing standard or anatomical PVP. The pre-, intra- and post-operative characteristics were compared betweene patients who started to void and the patients who developed post-operative urinary retention. Results: The study included 434 patients suitable for the study. Post-operative acute urinary retention occurred in 39 (9%). Patients with a lower prostate volume (P < .001), an adenoma volume lower than 40 mL (P < .001), and lower lasing time (P = .013) had a higher probability to develop pAUR at the univariate analysis. The multivariate logistic regression confirmed that lower lasing time (95% CI: 0.86-0.99, OR = 0.93, P = .046) and adenoma volume (95% CI: 0.89-0.98, OR = 0.94, P = .006) are correlated to pAUR. Furthermore IPSS ≥ 19 (95% CI: 1.19- 10.75, OR = 2.27, P = .023) and treatment with 5-ARI (95% CI: 1.05-15.03, OR = 3.98, P = .042) are risk factors for pAUR. Conclusion: In our series, post-operative acute urinary retention was related to low adenoma volume and lasing time, pre-operative IPSS ≥ 19 and 5-ARI intake. These data should be considered in deciding the best timing for urethral catheters removal

A Comparative Analysis of Extra-Embryonic Endoderm Cell Lines

Prior to gastrulation in the mouse, all endodermal cells arise from the primitive endoderm of the blastocyst stage embryo. Primitive endoderm and its derivatives are generally referred to as extra-embryonic endoderm (ExEn) because the majority of these cells contribute to extra-embryonic lineages encompassing the visceral endoderm (VE) and the parietal endoderm (PE). During gastrulation, the definitive endoderm (DE) forms by ingression of cells from the epiblast. The DE comprises most of the cells of the gut and its accessory organs. Despite their different origins and fates, there is a surprising amount of overlap in marker expression between the ExEn and DE, making it difficult to distinguish between these cell types by marker analysis. This is significant for two main reasons. First, because endodermal organs, such as the liver and pancreas, play important physiological roles in adult animals, much experimental effort has been directed in recent years toward the establishment of protocols for the efficient derivation of endodermal cell types in vitro. Conversely, factors secreted by the VE play pivotal roles that cannot be attributed to the DE in early axis formation, heart formation and the patterning of the anterior nervous system. Thus, efforts in both of these areas have been hampered by a lack of markers that clearly distinguish between ExEn and DE. To further understand the ExEn we have undertaken a comparative analysis of three ExEn-like cell lines (END2, PYS2 and XEN). PYS2 cells are derived from embryonal carcinomas (EC) of 129 strain mice and have been characterized as parietal endoderm-like [1], END2 cells are derived from P19 ECs and described as visceral endoderm-like, while XEN cells are derived from blastocyst stage embryos and are described as primitive endoderm-like. Our analysis suggests that none of these cell lines represent a bona fide single in vivo lineage. Both PYS2 and XEN cells represent mixed populations expressing markers for several ExEn lineages. Conversely END2 cells, which were previously characterized as VE-like, fail to express many markers that are widely expressed in the VE, but instead express markers for only a subset of the VE, the anterior visceral endoderm. In addition END2 cells also express markers for the PE. We extended these observations with microarray analysis which was used to probe and refine previously published data sets of genes proposed to distinguish between DE and VE. Finally, genome-wide pathway analysis revealed that SMAD-independent TGFbeta signaling through a TAK1/p38/JNK or TAK1/NLK pathway may represent one mode of intracellular signaling shared by all three of these lines, and suggests that factors downstream of these pathways may mediate some functions of the ExEn. These studies represent the first step in the development of XEN cells as a powerful molecular genetic tool to study the endodermal signals that mediate the important developmental functions of the extra-embryonic endoderm. Our data refine our current knowledge of markers that distinguish various subtypes of endoderm. In addition, pathway analysis suggests that the ExEn may mediate some of its functions through a non-classical MAP Kinase signaling pathway downstream of TAK1