West Nile virus surveillance using sentinel birds: results of eleven years of testing in corvids in a region of northern Italy

The natural transmission cycle of West Nile virus (WNV) involves birds as primary hosts and mosquitoes as vectors, but this virus can spread to mammals, human beings included. Asymptomatic infected donors pose a risk to the safety of blood transfusions and organ transplants, as WNV can be transmitted through these medical procedures. Since 2009, the region of Emilia-Romagna in northern Italy has been implementing an integrated surveillance system in order to detect WNV circulation in the environment at an early stage. Here we report the results of the two components of the surveillance system, the active testing of corvids and humans, and demonstrate that bird surveillance alone improves a surveillance system based solely on human case detection. As WNV risk reduction measures are applied on a provincial basis, we assessed the ability of this surveillance system component to detect virus circulation prior to the notification of the first human case for each province. Overall, 99 epidemic seasons were evaluated as a result of 11 years (2013–2023) of surveillance in the nine provinces of the region. In this period, 22,314 corvids were tested for WNV and 642 (2.9%) were found to be infected. WNV was generally first detected in birds in July, with sample prevalence peaks occurring between August and September. During the same period, 469 autochthonous human cases were notified, about 60% of which were reported in August. WNV was detected 79 times out of the 99 seasons considered. The virus was notified in birds 73 times (92.4%) and 60 times (75.9%) in humans. WNV was first or only notified in birds in 57 seasons (72.1%), while it was first or only notified in humans in 22 seasons (27.8%). Active surveillance in corvids generally allows the detection of WNV before the onset of human cases. Failure of virus detection occurred mainly in seasons where the number of birds tested was low. Our results show that active testing of a minimum of 3.8 corvids per 100 km2 provides a satisfactory timeliness in the virus detection, but for early detection of WNV it is crucial to test birds between mid-June and mid-August

Eleven Years of Health Monitoring in Wild Boars (Sus scrofa) in the Emilia-Romagna Region (Italy)

In recent years, the growth of wild ungulates has increased the focus on their health monitoring. In particular, the health status of wild boars is relevant for the economic impact on the pig industry. The Emilia-Romagna region activated a wildlife monitoring plan to better evaluate the health status of the wild boar population. Between 2011 and 2021, samples of found dead and hunted wild boar have been examined for trichinellosis, tuberculosis, brucellosis, african swine fever, classical swine fever, Aujeszky’s disease, swine vesicular disease, and swine influenza A. Trichinella britovi was identified in 0.001% of the examined wild boars; neither M. bovis nor M. tuberculosis were found in M. tuberculosis complex positive samples; 2.3% were positive for Brucella suis; 29.4% of the sera were positive for Aujeszky’s disease virus; and 0.9% of the samples were positive for swine influenza A virus. With an uncertain population estimate, the number of animals tested, the number of positives, and the sampling method do not allow us to make many inferences but suggest the need to implement and strengthen the existing surveillance activity, as it seems to be the only viable alternative for safeguarding animal and human health

Bioresorbable insertion aids for brain implantable flexible probes: a comparative study on silk fibroin, alginate, and disaccharides

Miniaturized, flexible, and biocompatible neural probes have the potential to circumvent the brain's foreign body response, but the problem of surgical implantation remains. Herein, a probe intended for implantation in the rat hippocampus is coated in four bioresorbable stiffeners to determine which is most effective in aiding insertion. The stiffeners (sucrose, maltose, silk fibroin, and alginate) are evaluated through mechanical, chemical, and dissolution tests. After coating with silk fibroin, the buckling force of the neural probe increases from 0.31 to 75.99 mN. This goes in accordance with subsequent successful insertion tests. Fourier transform infrared spectroscopy results demonstrate the increase in β-sheet content of silk fibroin samples after treatment (e.g., water annealing) and show relevant changes due to dehydration of the alginate hydrogel. Both qualitative and quantitative dissolution studies in artificial cerebrospinal fluid illustrate that alginate and silk fibroin outlasts the disaccharide stiffeners. In this work, a variety of multidisciplinary analyses are carried out to find the best bioresorbable stiffener for deep brain implantable devices with the highest buckling force, longest dissolution time, and the most tunable structure. For the first time, an alginate hydrogel is used as a stiffener to aid insertion, expanding its usefulness beyond neural tissue engineering

Comparison between American and European legislation in the therapeutical and alimentary bacteriophage usage

© Mattioli 1885.Bacteriophages, though discovered a century ago, still lag behind in the race of antimicrobials due to scarce information about their biology, pharmacology, safety and suitability as therapeutic agents. Although they possess several capabilities of practical utility in medicine, they are still unable to satisfy the regulatory standards set by the regulatory authorities in both United States (US) and European Union (EU). Bacteriophages and their products (lysins) are considered as drugs, therefore they should follow the same route of the chemical drugs in order to achieve regulatory approvals for commercial production and application. However, lack of definitive guidelines and regulations has rendered bacteriophages less attractive to pharmaceutical companies and funding agencies, making it difficult for clinicians and researchers to set up wide scale clinical trials in order to prove efficacy, safety and stability of bacteriophages and their products. In this review, we will discuss the current regulations for developing phages and phage-based products for therapeutic purposes in the US and EU. (www.actabiomedica.it)

Sequence analysis of ADARB1 gene in patients with familial bipolar disorder

BACKGROUND: The ADARB1 gene is located in 21q22.3 region, previously linked to familial bipolar disorder, and its product has a documented action in the editing of the pre-mRNA of glutamate receptor B subunit. Dysfunction of glutamatergic neurotransmission could play an important role in the pathophysiology of bipolar disorder (BD). Glutamate excitatory neurotransmission regulation is a possible mechanism of the initial effect of anticonvulsants in regulating mood. METHODS: To investigate the hypothesis of an involvement of ADARB1 gene in the BD, the ADARB1 cDNA has been cloned and sequenced in seven selected bipolar I disorder patients with evidence of familiarity of mood disorders. A detailed investigation of the gene nucleotide sequence in the open reading frame has been performed. RESULTS: No alteration in the sequence of the ADARB1 gene cDNA was found in any patient, except a common neutral polymorphism in three out of seven patients. CONCLUSIONS: Mutations in ADARB1 gene are not commonly associated with bipolar I disorder, therefore other genes in the 21q22 region could be associated with bipolar illness in some families, likely in the context of a multifactorial transmission model

Sequence analysis of ADARB1 gene in patients with familial bipolar disorder

Background: The ADARB1 gene is located in 21q22.3 region, previously linked to familial bipolar disorder, and its product has a documented action in the editing of the pre-mRNA of glutamate receptor B subunit. Dysfunction of glutamatergic neurotransmission could play an important role in the patophysiology of bipolar disorder (BD). Glutamate excitatory neurotransmission regulation is a possible mechanism of the initial effect of anticonvulsants in regulating mood. Methods: To investigate the hypothesis of an involvement of ADARB1 gene in the BD, the ADARB1 cDNA has been cloned and sequenced in seven selected bipolar I disorder patients with evidence of familiarity of mood disorders. A detailed investigation of the gene nucleotide sequence in the open reading frame has been performed. Results: No alteration in the sequence of the ADARB1 gene cDNA was found in any patient, except a common neutral polymorphism in three out of seven patients. Conclusions: Mutations in ADARB1 gene are not commonly associated with bipolar I disorder, therefore other genes in the 21q22 region could be associated with bipolar illness in some families, likely in the context of a multifactorial transmission model. © 2003 Elsevier B.V. All rights reserved

Multicenter prospective study of angiogenesis polymorphism validation in HCC patients treated with sorafenib. An Innovate study protocol

Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set

The first Italian blast-induced liquefaction test (Mirabello, Emilia-Romagna, Italy): description of the experiment and preliminary results.

none44Soil liquefaction can result in significant settlement and reduction of load-bearing capacity. Moreover, the increase and the accumulation of pore pressure during an earthquake and its post-seismic dissipation can generate permanent deformations and settlements. The quantitative evaluation of post-liquefaction settlements is of extreme importance for engineering purposes, i.e. for earthquake-resistant design of new buildings and safety evaluation of existing ones. Quantifying the extent of these phenomena is, however, rather difficult. Uncertainties arise from the stochastic nature of the earthquake loading, from the simplifications of soil models, and from the difficulty in establishing correlations between the pre-earthquake soil state and the post-seismic deformations. Field scale liquefaction tests, under controlled conditions, are therefore important for a correct quantification of these phenomena. Recent experiences (e.g. New Zealand, United States) show that liquefaction can be induced and monitored with field scale blast tests to study the related effects on soil geotechnical properties. Within this framework this paper introduces the preliminary results obtained from a research project on blast-induced liquefaction at the field scale; tests were performed at a trial site located in Mirabello (Ferrara, Italy), a village strongly affected by liquefaction phenomena during the 2012 Emilia Romagna earthquake. Invasive tests, such as piezocone, seismic dilatometer and down-hole tests, and non-invasive tests were carried out before and after the execution of two blast test sequences to study the variation in physical properties of the soils. Pore pressure transducers, settlement profilometers, accelerometers and an instrumented micropile were installed with the objective of measuring, during and after the detonations, the generation and subsequent dissipation of the pore pressure, the vertical deformations, and the blast-induced ground motions respectively. Variations in load distribution on deep foundations due to soil liquefaction were also evaluated on a test micropile instrumented with a strain gauge chain. Topographical surveys were carried out to measure ground surface settlements. Laboratory tests and trenches also provided increase understanding of the site characteristics.Soil liquefaction can result in significant settlement and reduction of load-bearing capacity. Moreover, the increase and the accumulation of pore pressure during an earthquake and its post-seismic dissipation can generate permanent deformations and settlements. The quantitative evaluation of post-liquefaction settlements is of extreme importance for engineering purposes, i.e. for earthquake-resistant design of new buildings and safety evaluation of existing ones. Quantifying the extent of these phenomena is, however, rather difficult. Uncertainties arise from the stochastic nature of the earthquake loading, from the simplifications of soil models, and from the difficulty in establishing correlations between the pre-earthquake soil state and the post-seismic deformations. Field scale liquefaction tests, under controlled conditions, are therefore important for a correct quantification of these phenomena. Recent experiences (e.g. New Zealand, United States) show that liquefaction can be induced and monitored with field scale blast tests to study the related effects on soil geotechnical properties. Within this framework this paper introduces the preliminary results obtained from a research project on blast-induced liquefaction at the field scale; tests were performed at a trial site located in Mirabello (Ferrara, Italy), a village strongly affected by liquefaction phenomena during the 2012 Emilia Romagna earthquake. Invasive tests, such as piezocone, seismic dilatometer and down-hole tests, and non-invasive tests were carried out before and after the execution of two blast test sequences to study the variation in physical properties of the soils. Pore pressure transducers, settlement profilometers, accelerometers and an instrumented micropile were installed with the objective of measuring, during and after the detonations, the generation and subsequent dissipation of the pore pressure, the vertical deformations, and the blast-induced ground motions respectively. Variations in load distribution on deep foundations due to soil liquefaction were also evaluated on a test micropile instrumented with a strain gauge chain. Topographical surveys were carried out to measure ground surface settlements. Laboratory tests and trenches also provided increase understanding of the site characteristics.noneAMOROSO SARA, MILANA GIULIANO, ROLLINS KYLE, COMINA CESARE, MINARELLI LUCA, MANUEL MARIA, MONACO PAOLA, FRANCESCHINI MARCO, ANZIDEI MARCO, LUSVARDI CAMERON, CANTORE LUCIANA, CARPENA ANDREA, CASADEI STEFANO1, CINTI FRANCESCA, CIVICO RICCARDO, COX BRADY, DE MARTINI PAOLO MARCO, DI GIULIO GIUSEPPE, DI NACCIO DEBORAH, DI STEFANO GIUSEPPE, FACCIORUSSO JOHANN, FAMIANI DANIELA, FIORELLI FEDERICO, FONTANA DANIELA, FOTI SEBASTIANO, MADIAI CLAUDIA, MARANGONI VALERIA, MARCHETTI DIEGO, MARCHETTI SILVANO, MARTELLI LUCA, MARIOTTI MAURO,MUSCOLINO ELENA, PANCALDI DAVIDE, PANTOSTI2 DANIELA, PASSERI FEDERICO, PESCI ARIANNA, ROMEO GIOVANNI, SAPIA VINCENZO, SMEDILE ALESSANDRA, STEFANI MARCO, TARABUSI GABRIELE, TEZA GIORDANO, VASSALLO MAURIZIO, VILLANI FABIOAmoroso, Sara; Milana, Giuliano; Rollins, Kyle; Comina, Cesare; Minarelli, Luca; Manuel, Maria; Monaco, Paola; Franceschini, Marco; Anzidei, Marco; Lusvardi, Cameron; Cantore, Luciana; Carpena, Andrea; Casadei, Stefano1; Cinti, Francesca; Civico, Riccardo; Cox, Brady; DE MARTINI PAOLO, Marco; DI GIULIO, Giuseppe; DI NACCIO, Deborah; DI STEFANO, Giuseppe; Facciorusso, Johann; Famiani, Daniela; Fiorelli, Federico; Fontana, Daniela; Foti, Sebastiano; Madiai, Claudia; Marangoni, Valeria; Marchetti, Diego; Marchetti, Silvano; Martelli, Luca; Mariotti, Mauro; Muscolino, Elena; Pancaldi, Davide; Pantosti2, Daniela; Passeri, Federico; Pesci, Arianna; Romeo, Giovanni; Sapia, Vincenzo; Smedile, Alessandra; Stefani, Marco; Tarabusi, Gabriele; Teza, Giordano; Vassallo, Maurizio; Villani, Fabi

Outcomes of a 3-year prospective surveillance in individuals at high-risk for pancreatic cancer

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a pre-clinical stage. In 2015 the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms seven years after the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) inception focusing on individuals with at least a 3-year follow-up or developing events before. Methods: HRI (subjects with family history or mutation carriers with/without family history were enrolled in 18 Centers. They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). Results: During the study period (June 2015 - September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/pre-malignancy-related events, and represented the study population. Median age was 51 (IQR 16). Familial PC cases (FPC) accounted for 81.4% of HRI, and individuals with pathogenic variant (PV) for 18.6%. Malignant (n=8) and pre-malignant (1 PanIN3) lesions were found in nine individuals. Five of these 8 cases occurred in PV carriers, four in FPC cases (two tested negative at germline testing, and two others were not tested). Three of the 8 PC were Stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5% and 3%, respectively. Median overall and disease-free survival of resected PC patients were 18 and 12 months (95%CI not computable). Considering HRI who underwent baseline imaging, six pancreatic neuroendocrine neoplasms (one resected) and one low-yield surgery (low-grade mixed-IPMN) were also reported. Conclusion: PC surveillance in a fully public healthcare system is feasible, safe, and leads to early PC or pre-malignant lesions diagnoses, mostly at baseline but also over time