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West Nile virus ( WNV) is a mosquito-transmitted Flavivirus belonging to the Japanese encephalitis antigenic complex of the Flaviviridae family. It is transmitted primarily by the bite of infected mosquitoes, particularly Culex spp. and Aedes/Ochlerotatus spp., which acquire the virus by feeding on viraemic birds. Humans, horses and other mammals are regarded as incidental or dead-end hosts. In the last decades, an increasing number of cases of WNV infection in horses and humans have been notified in the Mediterranean basin. In Tunisia, human cases of WNV-related meningoencephalitis were detected in 1997, 2003, 2007, 2010, 2011 and 2012. Based on the analysis of climatic and environmental conditions found in the locations where human cases have been reported in 2012, the aim of this study was to identify similar areas in Tunisia potentially at risk of disease occurrence. Data related to 85 neuroinvasive West Nile fever ( WNF) human cases were georeferenced and a set of environmental and climatic variables (wetlands and humid areas, normalized difference vegetation index (NDVI), temperatures and elevation, migratory bird settlements) were used in the analysis. Areas, ecologically similar to those where human cases were detected, were identified using the Mahalanobis distance statistic. A leave-one-out cross-validation was performed to validate the sensitivity of the model, and 78 of 85 points were correctly classified. [ABSTRACT FROM AUTHOR]

In August 2008, after 10 years of apparent silence, West Nile virus (WNV) infection re-emerged in northern Italy, spreading through the territories of three regions. In the following years, new cases occurred in the same area and additional foci of infection were observed in central and southern Italy, involving also Sicily and Sardinia islands. The Italian Ministry of Health ordered to test by RT-PCR all blood and organ donors from 15th June to 15th November of each year in the infected areas. The period at risk of WNV transmission was defined on the basis of literature data, but a more scientific estimation of the transmission season, under Italian circumstances, needs to be performed. A transitional model previously developed by other Authors was applied and adapted to Italian circumstances, to describe and quantify the WNV transmission cycle between birds and mosquitoes. Culex spp. was considered the main vector, and mosquito parameters were adapted to this genus. Magpies ( Pica pica) were considered the main bird host. The model was partially validated through the results of the entomological surveys carried out in central Italy and in Po Valley. The results of the transitional model permitted to calculate the basic reproduction number ( R0) during 2010 for the whole Italian territory at 1 km of spatial resolution, estimating the risk of WNV transmission during the year and creating detailed risk maps for Italy. The mean values of R0 for the whole Italy varied between 0.4 and 4.8, with values >1 from the end of May to the middle of September. The coastal and flat zones of Italy showed the highest R0 values. Although partially validated, the model showed a substantial acceptable capacity of defining the period at major risk of WNV transmission in Italy, helping Public health authorities in the application of appropriate and timely control and preventive measures. [ABSTRACT FROM AUTHOR]

Animal movements are a key factor in the spread of pathogens. Consequently, network analysis of animal movements is a well-developed and well-studied field. The relationships between animals facilitate the diffusion of infectious agents and, in particular, shared environments and close interactions can facilitate cross-species transmission. Cattle are often the focus of these studies since they are among the most widely distributed and traded species globally. This remains true for Italy as well, but with an important additional consideration. Indeed, another important productive reality in the peninsula is buffalo farming. These farms have an interesting characteristic: approximately two-thirds of them also rear cattle. This coexistence between cattle and buffalo could have an impact on the diffusion of pathogens. Given that buffalo farms are often overlooked in the literature, the primary goal of this work is to investigate the potential consequences of omitting buffalo from cattle network analyses. To investigate this impact, we will focus on Q fever, a disease that can infect both species and is present on the Italian territory and for which the impact of the buffalo population has not been thoroughly studied, and simulate its spread to the farms of both species through compartmental models. Our analysis reveals that despite the significant difference in network sizes, the unique characteristic of Italian buffalo farms makes the buffalo network essential for a comprehensive understanding of bovine disease dynamics in Italy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zoppi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aim of this study was to evaluate the effect of ylang-ylang ( Cananga odorata ) essential oil (YEO) on models of experimental arthritis, persistent inflammation, and nociception in mice. YEO treatment at doses of 100 and 200 mg/kg reduced the infiltration of leukocytes into the joint cavities of mice submitted to zymosan-induced arthritis 6 h and 7 days after arthritis induction. At these doses, YEO treatment reduced the formation of joint edema 4 and 6 h after arthritis induction, and at a dose of 200 mg/kg, YEO treatment reduced mechanical hyperalgesia 3 and 4 h after arthritis induction. At the dose of 200 mg/kg, YEO treatment reduced interleukin-6 (IL-6) levels and cartilage destruction in the zymosan-induced arthritis model, and reduced edema formation and mechanical hyperalgesia in the model of persistent inflammation (21 days) induced by complete Freund's adjuvant (CFA) in mice. YEO treatment at a dose of 200 mg/kg reduced the nociceptive response in experimental models of nociception induced by acetic acid and formalin. The YEO treatment reduced inflammatory parameters in the experimental arthritis model, and presented antiarthritic, anti-hyperalgesic, antinociceptive, and anti-inflammatory properties.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage damage. Anti-inflammatories are widely used in the management of RA, but they can have side effects such as gastrointestinal and/or cardiovascular disorders. Studies published by our group showed that the synthesis of hybrid triazole analogs neolignan-celecoxib containing the substituent groups sulfonamide (L15) or carboxylic acid (L18) exhibited anti-inflammatory activity in an acute model of inflammation, inhibited expression of P-selectin related to platelet activation and did not induce gastric ulcer, minimizing the related side effects. In continuation, the present study evaluated the anti-inflammatory effects of these analogs in an experimental model of arthritis and on the functions of one of the important cells in this process, macrophages. Mechanical hyperalgesia, joint edema, leukocyte recruitment to the joint and damage to cartilage in experimental arthritis and cytotoxicity, spread of disease, phagocytic activity and nitric oxide (NO) and hydrogen peroxide production by macrophages were evaluated. Pre-treatment with L15 and L18 reduced mechanical hyperalgesia, joint edema and the influx of leukocytes into the joint cavity after different periods of the stimulus. The histological evaluation of the joint showed that L15 and L18 reduced cartilage damage and there was no formation of rheumatoid pannus. Furthermore, L15 and L18 were non-cytotoxic. The analogs inhibited the spreading, the production of NO and hydrogen peroxide. L15 decreased the phagocytosis. Therefore, L15 and L18 may be potential therapeutic prototypes to treat chronic inflammatory diseases such as RA., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Ethnopharmacological Relevance: The leaves of Miconia albicans have been extensively used as a traditional medicine to treat inflammation, infection, arthritis, joint pain, and analgesia, which can be purchased easily. Nevertheless, the scientific evidence of chemical profile identification and toxicity investigation is meager., Aim of the Study: This study aimed to determine the chemical profile of Miconia albicans aqueous extract (MAAE), to investigate its anti-inflammatory and hyperalgesic effects, and toxicity (acute and repeated-dose oral) in vivo studies., Materials and Methods: MAAE was obtained by infusion method and its chemical constituents were analyzed and annotated by LC-DAD-MS. The in vivo tests were performed with male and female Swiss mice. Toxicity studies were examined by acute (2000 mg/kg) and repeated-dose oral assays (51.2; 256; 1280 mg/kg); anti-inflammatory evaluation was performed by paw edema and leukocyte migration, and anti-hyperalgesic properties were analyzed by abdominal writhing induced by acetic acid and formalin. The animals were treated by oral means with 51.2, 256, and 1280 mg/kg of MAAE., Results: Twenty-four compounds were annotated from MAAE by LC-DAD-MS, such as ellagitannins, ellagic acid derivatives, flavan-3-ol, and O-glycosylated compounds, including flavonols, triterpenes, and megastigmanes. MAAE induced no significant toxicological effects in the acute and repeated-dose oral assays at lower doses and no histological changes were observed. Hematological and biochemical showed no significant alterations. The oral administration of MAAE 256 mg/kg inhibited the edematogenic effect and reduced the leukocyte migration. In addition, MAAE decreased the abdominal writhings induced by acetic acid and the paw-licking time by formalin assay., Conclusion: MAAE showed a significant reduction in inflammatory levels and leukocyte migration, revealing anti-hyperalgesic properties. Additionally, MAAE revealed no acute and repeated-doses toxicities., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Endoleaks represent a main issue of endovascular approach of thoracic aorta diseases and their treatment continue to be challenging. According to some authors, type II endoleaks sustained by intercostal arteries should not be treated because of the technical difficulties. However, the persistence of a pressurized aneurysmal may confer an ongoing risk of enlargement and/or aortic rupture. We describe the successful treatment of type II endoleak in 2 patients with an intercostal artery's access. In both cases, the endoleak was discovered during follow-up and was treated with its direct coil embolization under local anaesthesia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Brucellosis is one of the world's major zoonotic pathogens and is responsible for enormous economic losses as well as considerable human morbidity in endemic areas. Definitive control of human brucellosis requires control of brucellosis in livestock through practical solutions that can be easily applied to the field. In Italy, brucellosis remains endemic in several southern provinces, particularly in Sicily Region. The purpose of this paper is to describe the developed brucellosis model and its applications, trying to reproduce as faithfully as possible the complex transmission process of brucellosis accounting for the mixing of grazing animals. The model focuses on the contaminated environment rather than on the infected animal, uses real data from the main grazing areas of the Sicily Region, and aims to identify the best control options for minimizing the spread (and the prevalence) and to reach the eradication within the concerned areas. Simulation results confirmed the efficacy of an earlier application of the controls, showed the control should take place 30 days after going to pasture, and the culling time being negligible. Moreover, results highlighted the importance of the timing of both births and grazing pastures (and their interaction) more than other factors. As these factors are region‑specific, the study encourages the adoption of different and new eradication tools, tuned on the grazing and commercial behavior of each region. This study will be further extended to improve the model's adaptability to the real world, with the purpose of making the model an operational tool able to help decision makers in accelerating brucellosis eradication in Italy.

An 80-year-old man with a chronic penetrating atherosclerotic ulcer was not a candidate for open surgical repair owing to the presence of diffuse vascular atherosclerosis and a deep ulcerative lesion originating at the level of the aortic arch concavity. No appropriate endovascular landing zone was present in arch zones 1 or 2. However, a totally endovascular branched arch repair involving transapical delivery of the three branches was successful., (© 2023 The Author(s).)

Background: Complex aortic pathology still represents an open issue in contemporary endovascular management, with continuous technological advancement being introduced in practice over time aiming to improve outcomes. Thus far, the dualism between the fenestrated and branched configuration for visceral artery revascularization is yet unsolved, with each approach having its own pros and cons. The inner branched technology for endovascular aneurysm repair (iBEVAR) aims to take the best out of both strategies, offering wide applicability and stable bridging stent sealing. The objective of this study was to evaluate the early outcomes obtained with a single manufacturer custom-made inner-branched endograft in a multicenter Italian experience., Methods: All patients consecutively treated with E-xtra design devices in three Italian facilities were enrolled. Anatomic characteristics and perioperative data were analyzed. The main objective was to asses technical and clinical success after iBEVAR. Secondary end points were overall survival, aortic-related mortality, target visceral vessel (TVV) patency, and freedom from target vessel instability during follow-up., Results: From 2016 to 2021, 45 patients were treated with an E-xtra design device revascularizing at least one visceral vessel through an inner branch. The mean age at the time of the procedure was 71.1 ± 9.3 years and 77.8% were males. The total number of target visceral arteries to be bridged with an inner branch was 159. The extent of aortic repair was thoracoabdominal in 91.1% of the cases. Technical success was achieved in 93.3% of the procedures (42/45) with all failures owing to a type I endoleak at final angiography. Each TVV was successfully connected to the graft's main body as planned without complications. Following their intervention, five patients developed spinal cord ischemia and in three of these cases symptoms persisted after discharge (6.7%). At 30 days clinical success was 93.3% (42/45). No death as well as no TVV thrombosis occurred within 30 days from the primary procedures. The mean follow-up was 22.8 ± 14.2 months. The Kaplan-Meier estimate of overall survival and TVV patency at 36 months were 83.9% and 95.9%, respectively., Conclusions: Inner branches seem to be a promising technology in the complex aortic repair landscape, with an applicability ranging from type II thoracoabdominal aneurysm to type I endoleak repair after infrarenal endografting. Whether iBEVAR could offer results comparable with those provided by fenestrated/branched endovascular aneurysm repair in terms of target vessel patency and stent stability is yet to be established and further studies are, therefore, needed., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

West Nile virus (WNV) is a mosquito-borne virus potentially causing serious illness in humans and other animals. Since 2004, several studies have highlighted the progressive spread of WNV Lineage 2 (L2) in Europe, with Italy being one of the countries with the highest number of cases of West Nile disease reported. In this paper, we give an overview of the epidemiological and genetic features characterising the spread and evolution of WNV L2 in Italy, leveraging data obtained from national surveillance activities between 2011 and 2021, including 46 newly assembled genomes that were analysed under both phylogeographic and phylodynamic frameworks. In addition, to better understand the seasonal patterns of the virus, we used a machine learning model predicting areas at high-risk of WNV spread. Our results show a progressive increase in WNV L2 in Italy, clarifying the dynamics of interregional circulation, with no significant introductions from other countries in recent years. Moreover, the predicting model identified the presence of suitable conditions for the 2022 earlier and wider spread of WNV in Italy, underlining the importance of using quantitative models for early warning detection of WNV outbreaks. Taken together, these findings can be used as a reference to develop new strategies to mitigate the impact of the pathogen on human and other animal health in endemic areas and new regions.

Background: Tunisia has experienced several West Nile virus (WNV) outbreaks since 1997. Yet, there is limited information on the spatial distribution of the main WNV mosquito vector Culex pipiens suitability at the national level., Objectives: In the present study, our aim was to predict and evaluate the potential and current distribution of Cx. pipiens in Tunisia., Methods: To this end, two species distribution models were used, i.e. MaxEnt and Random Forest. Occurrence records for Cx. pipiens were obtained from adult and larvae sampled in Tunisia from 2014 to 2017. Climatic and human factors were used as predictors to model the Cx. pipiens geographical distribution. Mean decrease accuracy and mean decrease Gini indices were calculated to evaluate the importance of the impact of different environmental and human variables on the probability distribution of Cx. pipiens., Results: Suitable habitats were mainly distributed next to oases, in the north and eastern part of the country. The most important predictor was the population density in both models. The study found out that the governorates of Monastir, Nabeul, Manouba, Ariana, Bizerte, Gabes, Medenine and Kairouan are at highest epidemic risk., Conclusions: The potential distribution of Cx. pipiens coincides geographically with the observed distribution of the disease in humans in Tunisia. Our study has the potential for driving control effort in the fight against West Nile vector in Tunisia., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The aim of this study is to evaluate the efficacy of Baccharis trimera infusion on high-fat diet-induced metabolic disorders in mice and macrophages activation. This study evaluated obesity, insulin resistance, dyslipidemia and hepatic steatosis induced by a high-fat diet in Swiss mice. Cellular parameters in macrophages, such as cell viability (MTT), the production and release of nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ), cell spreading, cell adhesion and phagocytosis were determined. Our results showed that treatment with B. trimera prevented the mentioned conditions, except for the production of hydrogen peroxide. B. trimera prevented the development of obesity and associated comorbidities, as well as activation of macrophages. In conclusion, B. trimera is able to prevent obesity and metabolic disorders and macrophages activation, minimizing inflammation and validating the popular use of this plant tea.

From 24 December 2020 to 8 February 2021, 163 cases of SARS-CoV-2 Alpha variant of concern (VOC) were identified in Chieti province, Abruzzo region. Epidemiological data allowed the identification of 14 epi-clusters. With one exception, all the epi-clusters were linked to the town of Guardiagrele: 149 contacts formed the network, two-thirds of which were referred to the family/friends context. Real data were then used to estimate transmission parameters. According to our method, the calculated Re(t) was higher than 2 before the 12 December 2020. Similar values were obtained from other studies considering Alpha VOC. Italian sequence data were combined with a random subset of sequences obtained from the GISAID database. Genomic analysis showed close identity between the sequences from Guardiagrele, forming one distinct clade. This would suggest one or limited unspecified viral introductions from outside to Abruzzo region in early December 2020, which led to the diffusion of Alpha VOC in Guardiagrele and in neighbouring municipalities, with very limited inter-regional mixing., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In a temperature-increasing scenario, due to global warming, the individual thermic resilience of the male assumes a crucial role in the reproductive efficiency of a male since the thermic stress, such as the inability of the male to reduce body or regional temperature on a physiological level, impairs testicular function. In this study, the effect of the environmental conditions on the fresh semen quality, in terms of volume, concentration, total sperm in the ejaculate, total motility, normal morphology, membrane integrity, and discarding rate, were compared longitudinally in Belgian Blue (BB) and Brown Swiss (BS) bulls. The environmental conditions, summarized in the mean temperature-humidity index (THI), were calculated on the day of collection, as well as 7 days (epididymal maturation), 35 days (late spermatogenesis), and 70 days (early spermatogenesis) before the collection, to reflect spermatogenesis time. Our findings showed that limited seasonal effects were present in the semen quality of BS bulls. On the other hand, in BB bulls lower semen quality was found between July and November, with a different timing depending on the seminal parameter. This effect of the season on BB semen parameters appears to be related to the THI. The data presented in this study shows that the temperature and humidity, summarized in THI, could affect the semen quality of the bull on breed basis, given that volume, concentration, total sperm in the ejaculate, total motility, membrane integrity, and sperm normal morphology were significantly reduced by an increasing THI in the Belgian Blue bulls, but not in Brown Swiss bulls., (© 2021. ISB.)

Ethnopharmacological Relevance: Lantana canescens is popularly known in Brazil as "cidreirinha" or "chumbinho-branco". It is found in Pantanal biome and its flowers and leaves are used in traditional medicine to treat pain and inflammation. Information about this species is limited to the activity of isolated essential oils. Studies with different extracts, composition, and biological properties are still scarce., Aim of This Study: The objective of this study was to evaluate the anti-inflammatory and anti-hyperalgesic activity of the hydroethanolic extract of L. canescens aerial parts., Materials and Methods: The hydroethanolic extract L. canescens aerial parts (HELc) was analyzed using HPLC-DAD-EM. Male and female Swiss mice weighing 18-25 g were used in the in vivo assays. Acute toxicity was assessed (2000 mg/kg); anti-inflammatory activity through paw edema, mast cell degranulation and peritonitis, and anti-hyperalgesic activity through abdominal writhing assays induced by acetic acid and formalin sensitization, were evaluated using the doses of 3, 30 and 300 mg/kg., Results: The phytochemical characterization of HELc confirmed the presence of glycosylated iridoids (theveside, theviridoside), verbascosides and flavonoids. The HELc did not present toxicity in the evaluated dose. HELc reduced formation of paw edema, degranulation of peritoneal mast cells and infiltration of polymorphonuclear cells into the animals peritoneal cavity. In addition, HELc decreased the number of abdominal writhing induced by acetic acid and the time of paw licking in the evaluation of formalin sensitization., Conclusions: These results confirm the anti-inflammatory and anti-hyperalgesic effects of hydroethanolic extract of L. canescens, validating the use of this plant in folk medicine., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To identify the risk factors associated with patency loss after bailout stenting with third-generation hybrid heparin-bonded nitinol stent of the femoropopliteal segment., Methods: Prospective, multicenter, single-arm registry including 156 patients (50 females, mean age 72 ± 11 years) subjected, from February 2017 to December 2018, to provisional stenting with Gore Tigris vascular stent of the distal superficial femoral artery, with or without involvement of the popliteal artery, in 9 different centers. The 194 lesions, with Rutherford score ≥ 3, were stented in case of recoil, dissection or residual stenosis not responding to percutaneous trans-luminal angioplasty (PTA). The follow-up (FU) was performed with clinical evaluation and duplex ultrasound (DUS) at 1, 6 and 12 months., Results: The primary patency rate was 99(95%CI 98-100)% at 1 month, 86(80-92)% at 6 months and 81(74-88)% at-12 months. After patency loss, 13/23 (56.5%) patients were re-treated, yielding a primary assisted patency of 91(86-96)% at 6 months and 88(82-94)% at 12 months and a secondary patency of 94(90-98)% at 6 months and 90(84-95)% at 12 months. Rutherford score ≥ 4 (p = 0.03) and previous severe treatments (p = 0.01) were identified as risk factors for early patency loss during FU. The involvement of the popliteal artery was not an independent risk factor for loss of patency., Conclusions: The bailout stenting of the femoropopliteal segment with third-generation nitinol stents is a safe and effective option in case of recoil, dissection or residual stenosis not responding to PTA. Critical limb ischemia and history of previous major treatment at the same level are significant prognostic factors for patency loss during FU., (© 2021. Italian Society of Medical Radiology.)

Pecorino di Farindola is a typical cheese produced in the area surrounding the village of Farindola, located in the Abruzzo Region (central Italy), unique among Italian cheese because only raw ewe milk and pig rennet are used for its production. In the literature it is well documented that raw milk is able to support the growth of pathogenic microorganisms such as Listeria monocytogenes. Predictive microbiology can be useful in order to predict growth-death kinetics of pathogenic bacteria, on the basis of known environmental conditions. Aim of this study was to compare predictions obtained from a model, originally designed to predict the kinetics of L. monocytogenes in the dynamic growth-death environment of drying fresh sausage, with the results of challenge tests performed during the ripening of Pecorino di Farindola produced from artificially contaminated raw ewe milk. A challenge test was carried out using ewe raw milk inoculated with L. monocytogenes, in order to produce Pecorino di Farindola cheese stored at 18 °C for 149 days of ripening. During the ripening period, pH and a w values decreased in all samples analysed; lactic acid bacteria become the prevailing microbial population, while for L. monocytogenes a period of stability (neither growth nor death) followed the initial situation. The growth inhibition and the following inactivation may mostly be due to competition with the autochthonous microbiota and to the reduction of water activity. Mathematical modelling was used in order to predict microbial kinetics in the dynamic ripening environment, joining growth and death patterns in a continuous way, and including the highly uncertain growth/no growth range separating the two regions. The effect of lactic acid bacteria on the growth of pathogens was also included. Predicted microbial kinetics were satisfactory, as confirmed by the absence of statistically significant difference between observed and predicted values (p > 0.05). The present study proved, via challenge tests, that a dynamic growth/death model, previously used for a meat product, can be fruitfully used in cheese characterized by active competitive microbiota and progressive drying during ripening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In February 2020, Italy became the epicenter for COVID-19 in Europe, and at the beginning of March, the Italian Government put in place emergency measures to restrict population movement. Aim of our analysis is to provide a better understanding of the epidemiological context of COVID-19 in Italy, using commuting data at a high spatial resolution, characterizing the territory in terms of vulnerability. We used a Susceptible-Infectious stochastic model and we estimated a municipality-specific infection contact rate () to capture the susceptibility to the disease. We identified in Lombardy, Veneto and Emilia Romagna regions (52% of all Italian cases) significant clusters of high , due to the simultaneous presence of connections between municipalities and high population density. Local simulated spreading in regions, with different levels of infection observed, showed different disease geographical patterns due to different values and commuting systems. In addition, we produced a vulnerability map (in the Abruzzi region as an example) by simulating the epidemic considering each municipality as a seed. The result shows the highest vulnerability values in areas with commercial hubs, close to the highest populated cities and the most industrial area. Our results highlight how human mobility can affect the epidemic, identifying particular situations in which the health authorities can promptly intervene to control the disease spread., Competing Interests: The authors declare no conflict of interest.

Emerging and re-emerging infectious diseases are a significant public and animal health threat. In some zoonosis, the early detection of virus spread in animals is a crucial early warning for humans. The analyses of animal surveillance data are therefore of paramount importance for public health authorities to identify the appropriate control measure and intervention strategies in case of epidemics. The interaction among host, vectors, pathogen and environment require the analysis of more complex and diverse data coming from different sources. There is a wide range of spatiotemporal methods that can be applied as a surveillance tool for cluster detection, identification of risk areas and risk factors and disease transmission pattern evaluation. However, despite the growing effort, most of the recent integrated applications still lack of managing simultaneously different datasets and at the same time making available an analytical tool for a complete epidemiological assessment. In this paper, we present EpiExploreR, a user-friendly, flexible, R-Shiny web application. EpiExploreR provides tools integrating common approaches to analyze spatiotemporal data on animal diseases in Italy, including notified outbreaks, surveillance of vectors, animal movements data and remotely sensed data. Data exploration and analysis results are displayed through an interactive map, tables and graphs. EpiExploreR is addressed to scientists and researchers, including public and animal health professionals wishing to test hypotheses and explore data on surveillance activities.

Ecoregionalization is the process by which a territory is classified in similar areas according to specific environmental and climatic factors. The climate and the environment strongly influence the presence and distribution of vectors responsible for significant human and animal diseases worldwide. In this paper, we developed a map of the eco-climatic regions of Italy adopting a data-driven spatial clustering approach using recent and detailed spatial data on climatic and environmental factors. We selected seven variables, relevant for a broad set of human and animal vector-borne diseases (VBDs): standard deviation of altitude, mean daytime land surface temperature, mean amplitude and peak timing of the annual cycle of land surface temperature, mean and amplitude of the annual cycle of greenness value, and daily mean amount of rainfall. Principal Component Analysis followed by multivariate geographic clustering using the k-medoids technique were used to group the pixels with similar characteristics into different ecoregions, and at different spatial resolutions (250 m, 1 km and 2 km). We showed that the spatial structure of ecoregions is generally maintained at different spatial resolutions and we compared the resulting ecoregion maps with two datasets related to Bluetongue vectors and West Nile Disease (WND) outbreaks in Italy. The known characteristics of Culicoides imicola habitat were well captured by 2/22 specific ecoregions (at 250 m resolution). Culicoides obsoletus/scoticus occupy all sampled ecoregions, according to its known widespread distribution across the peninsula. WND outbreak locations strongly cluster in 4/22 ecoregions, dominated by human influenced landscape, with intense cultivations and complex irrigation network. This approach could be a supportive tool in case of VBDs, defining pixel-based areas that are conducive environment for VBD spread, indicating where surveillance and prevention measures could be prioritized in Italy. Also, ecoregions suitable to specific VBDs vectors could inform entomological surveillance strategies., Competing Interests: The authors have declared that no competing interests exist.

Bovine viral diarrhea (BVD) is a viral disease that affects cattle and that is endemic to many European countries. It has a markedly negative impact on the economy, through reduced milk production, abortions, and a shorter lifespan of the infected animals. Cows becoming infected during gestation may give birth to Persistently Infected (PI) calves, which remain highly infective throughout their life, due to the lack of immune response to the virus. As a result, they are the key driver of the persistence of the disease both at herd scale, and at the national level. In the latter case, the trade-driven movements of PIs, or gestating cows carrying PIs, are responsible for the spatial dispersion of BVD. Past modeling approaches to BVD transmission have either focused on within-herd or between-herd transmission. A comprehensive portrayal, however, targeting both the generation of PIs within a herd, and their displacement throughout the country due to trade transactions, is still missing. We overcome this by designing a multiscale metapopulation model of the spatial transmission of BVD, accounting for both within-herd infection dynamics, and its spatial dispersion. We focus on Italy, a country where BVD is endemic and seroprevalence is very high. By integrating simple within-herd dynamics of PI generation, and the highly-resolved cattle movement dataset available, our model requires minimal arbitrary assumptions on its parameterization. We use our model to study the role of the different productive contexts of the Italian market, and test possible intervention strategies aimed at prevalence reduction. We find that dairy farms are the main drivers of BVD persistence in Italy, and any control strategy targeting these farms would lead to significantly higher prevalence reduction, with respect to targeting other production compartments. Our multiscale metapopulation model is a simple yet effective tool for studying BVD dispersion and persistence at country level, and is a good instrument for testing targeted strategies aimed at the containment or elimination of this disease. Furthermore, it can readily be applied to any national market for which cattle movement data is available., (Copyright © 2019. Published by Elsevier B.V.)

The endemic circulation of bovine brucellosis in cattle herds has a markedly negative impact on economy, due to decreased fertility, increased abortion rates, reduced milk and meat production. It also poses a direct threat to human health. In Italy, despite the long lasting efforts and the considerable economic investment, complete eradication of this disease still eludes the southern regions, as opposed to the northern regions that are disease-free. Here we introduced a novel quantitative network-based approach able to fully exploit the highly resolved databases of cattle trade movements and outbreak reports to yield estimates of the vulnerability of a cattle market to brucellosis. Tested on the affected regions, the introduced vulnerability indicator was shown to be accurate in predicting the number of bovine brucellosis outbreaks (Spearman r= 0.82, p= 0.04), thus confirming the suitability of our tool for epidemic risk assessment. We evaluated the dependence of regional vulnerability to brucellosis on a set of factors including premises spatial distribution, trading patterns, farming practices, herd market value, compliance to outbreak regulations, and exploring different epidemiological conditions. Animal trade movements were identified as a major route for brucellosis spread between farms (r=0.85,p<10 -5 between vulnerability and number of inbound movements), with an additional potential risk attributed to the use of shared pastures (r=0.4,p=0.04). By comparing the vulnerability of disease-free regions in the north to affected regions in the south, we found that more intense trade and higher market value of the cattle sector in the north (r=0.56,p=0.01) likely inducing more efficient biosafety measures, together with poor compliance to trade restrictions following outbreaks in the south were key factors explaining the diverse success in eradicating brucellosis. Our modeling scheme is both synthetic and effective in gauging regional vulnerability to brucellosis persistence. Its general formulation makes it adaptable to other diseases and host species, providing a useful tool for veterinary epidemiology and policy assessment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The implementation of the European Union strategy for polychlorodibenzo-dioxins and -furans (PCDD/Fs), and dioxin-like polychlorobiphenyls (DL-PCBs) is determining a general reduction of their presence in the environment and in the food chain. The most important route for human exposure to these substances is food consumption and, as a consequence, a progressive decrease of their dietary intake has been observed in the last decades. In this context, it seemed worth updating the PCDD/F and DL-PCB intake estimation for the Italian population. A total of 2659 samples of food of animal and vegetable origin analyzed for PCDD/Fs and DL-PCBs in the period 2013-2016 by accredited official laboratories and the national food consumption database were considered for the dietary intake assessment in different age groups of the Italian general population The median cumulative intake estimates expressed as pg WHO-TEQ/kg body weight per day and computed with a deterministic and a probabilistic approach were 1.40-1.52 for children, 0.82-0.85 for adolescents, and 0.64-0.61 for adults, respectively. Such results confirm the decreasing trend of PCDD/F and DL-PCB dietary intake even though the Tolerable Daily Intake (TDI) value of 2 WHO-TEQ/kg body weight per day is exceeded at the 95th percentile for all age groups, with children as sensitive group. Most contributing food categories to the intake resulted fish, food of vegetable origin, and cheese. A sensitivity analysis was also performed to calculate the target contamination levels able to keep the dietary exposure below the TDI. Computed target levels fall between P50 and P97 of the occurrence distribution of the main food groups, meaning that most of the Italian food production can be considered safe., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Anal fissure is a tear in the epitelial lining of the anal canal. This is a very common anorectal disorder, but the choice of treatment is unclear. Sphincterotomy is effective but it is affected by a high risk of fecal incontinence. Manual anal stretch is aN efficacious, economic and safe maneuver. The aim of this prospective study was to assess the safety and effectiveness of anal stretch in resolving chronic anal fissures., Methods: Twenty-five patients with a clinical diagnosis of chronic anal fissure were submitted to anal stretch. All patients were submitted to anal stretch, after clinical evaluation. All patients were studied at basal time, and at 7 days, 3, 6 and 12 months after the treatment., Results: At 3 months and 6 months after the anal stretch, 88% and 94% of patients showed a resolution of anal fissures and only 12% have relapsed at 12 months, without complications, such as faecal incontinence., Conclusions: The anal stretch appears to induce better resolution of chronic anal fissure with a very low risk of fecal incontinence.

Background: An anal fissure (AF) is a tear in the epithelial lining of the anal canal. This is a very common condition, but the choice of treatment is unclear. The use of anal dilators is effective, economic, and safe. The aim of the study was to compare the efficacy of two conservative treatments, the use of anal dilators or a finger for anal dilatation, in reducing anal pressure and resolving anal fissures., Methods: Fifty patients with a clinical diagnosis of AF were randomly assigned to one of the treatments, self-massage of the anal sphincter (group A, 25 patients) or passive dilatation using dilators (group B, 25 patients). All patients were evaluated at baseline, at the end of treatment, and after 12 weeks and 6 months. Pain was measured using a visual analog scale., Results: After the treatment, 60% of patients treated with dilators and 80% of patients treated with anal self-massage using a finger showed disappearance of their anal fissures. A comparison between signs and symptoms reported by the patients in the two groups showed a statistically significant reduction in anal pain (group A, P=0.0001; group B, P=0.0001) and bleeding after defecation (group A, P=0.001, group B, P=0.001). At 6 months after treatment, a significantly greater reduction in anal pain was observed in Group A compared to Group B (P=0.02)., Conclusion: The use of anal self-massage with a finger appears to induce a better resolution of acute anal fissure than do anal dilators, and in a shorter time., Competing Interests: Conflict of Interest: None

Competing Interests: Conflict of Interest: None

In recent years researchers have investigated a growing number of weighted heterogeneous networks, where connections are not merely binary entities, but are proportional to the intensity or capacity of the connections among the various elements. Different degree centrality measures have been proposed for this kind of networks. In this work we propose weighted degree and strength centrality measures (WDC and WSC). Using a reducing factor we correct classical centrality measures (CD) to account for tie weights distribution. The bigger the departure from equal weights distribution, the greater the reduction. These measures are applied to a real network of Italian livestock movements as an example. A simulation model has been developed to predict disease spread into Italian regions according to animal movements and animal population density. Model's results, expressed as infected regions and number of times a region gets infected, were related to weighted and classical degree centrality measures. WDC and WSC were shown to be more efficient in predicting node's risk and vulnerability. The proposed measures and their application in an animal network could be used to support surveillance and infection control strategy plans., Competing Interests: The authors have declared that no competing interests exist.

In 2012, six years after the previous epidemic, Bluetongue virus serotype 1 (BTV-1) re-emerged in Sardinia causing a limited number of outbreaks. Due to impossibility of implementing a vaccination campaign, the BTV-1 then spread all over the island in 2013 with about 7,000 outbreaks and, in September 2013, the virus reached Central Italy, with a limited number of outbreaks located along the Tyrrhenian coast. The surveillance system in place in Italy detected viral circulation during the following winter, when a few seroconversions were notified. Starting from mid July 2014, a huge number of outbreaks were reported and the disease spread toward inland territories, affecting Umbria, Abruzzo and Marche. In 2014, BTV-1 affected areas where Culicoides species belonging to the Obsoletus and Pulicaris complexes were identified as main vectors. The analysis of temperature and rainfall in Central Italy revealed a significant warmer winter (2013-2014) and a cooler and rainy summer season (2014). These climatic aspects might have certainly favored the overwintering of the virus in local vector or host populations in the Tyrrhenian coast, and, then, the spread of the virus to the rest of Central Italy. However, the heavy circulation of BTV-1 and the severity of clinical outbreaks recorded leave a number of 'open questions' that are currently under investigations.

Food-borne campylobacteriosis is caused mainly by the handling or consumption of undercooked chicken meat or by the ingestion of contaminated raw milk. Knowledge about the contributions of different food sources to gastrointestinal disease is fundamental to prioritize food safety interventions and to establish proper control strategies. Assessing the genetic diversity among Campylobacter species is essential to our understanding of their epidemiology and population structure. We molecularly characterized 56 Campylobacter jejuni isolates (31 from patients hospitalized with gastroenteritis, 17 from raw milk samples, and 8 from chicken samples) using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) in order to trace the source of the disease. We also used a population genetic approach to investigate the source of the human cases from six different reservoirs of infection. MLST identified 25 different sequence types and 11 clonal complexes (CCs) (21, 658, 206, 353, 443, 48, 61, 257, 1332, 354, 574) and these included several alleles not cited previously in the PubMLST international database. The most prevalent CCs were 21, 206, and 354. PFGE showed 34 pulsotypes divided between 28 different clusters. At the fine scale, by means of PFGE and MLST, only two human cases were linked to raw milk, while one case was linked to chicken meat. The investigation revealed the presence of several genotypes among the human isolates, which probably suggests multiple foci for the infections. Finally, the source attribution model we used revealed that most cases were attributed to chicken (69.75%) as the main reservoir in Italy, followed to a lesser extent by the following sources: cattle (8.25%); environment (6.28%); wild bird (7.37%); small ruminant (5.35%), and pork (2.98%). This study confirms the importance of correlating epidemiological investigations with molecular epidemiological data to better understand the dynamics of infection.

Monophasic variant of Salmonella enterica subspecies enterica serovar Typhimurium (monophasic S. Typhimurium), with antigenic structure 1,4,[5],12:i:-, appears to be of increasing importance in Europe. In Italy, monophasic S. Typhimurium represented the third most frequent Salmonella serovar isolated from human cases between 2004 and 2008. From June 2013 to October 2014, a total of 206 human cases of salmonellosis were identified in Abruzzo region (Central Italy). Obtained clinical isolates characterised showed S. Typhimurium 1,4,[5],12:i:- with sole resistance to nalidixic acid, which had never been observed in Italy in monophasic S. Typhimurium, neither in humans nor in animals or foods. Epidemiological, microbiological and environmental investigations were conducted to try to identify the outbreak source. Cases were interviewed using a standardised questionnaire and microbiological tests were performed on human as well as environmental samples, including samples from fruit and vegetables, pigs, and surface water. Investigation results did not identify the final vehicle of human infection, although a link between the human cases and the contamination of irrigation water channels was suggested.

Aim: In prolapsed internal hemorrhoids exposed outside the anus, manually reducing the prolapse with 48 hours of commencement of anal pain, decreased the progression of thrombosis. The aim of our study was to evaluate the effects of manual reduction of the inflamed piles hemorrhoids., Materials of Study: Eleven patients, 7 males and 4 pregnant females (in early post partum) with an average age of 34 years ± 8 (range 23- 52) were enrolled with anal pain cause by haemorrhoidal congestion, but prior to full blown thrombosis. Patients underwent a manual reduction of the external prolapsed haemorrhoidal plexus. In the 48 hours following the procedure, patients were instructed on how to insert any prolapsed hemorrhoid (piles) themselves. Pain intensity was measured using the visual analog scale (VAS) at time of consultation and then 10 days after the reduction., Results: At day 10 following treatment we observed a statistically significant reduction in anal swelling (11 vs 1, n° pzt; p = 0.001), anal pain (11 vs 2, n° pzt; p = 0.001) and VAS score (8.6 ± 0.7 vs 0.4 ± 1.2; p = 0.001). Two patients (18%) underwent surgical haemorrhoidectomy sec. Milligan Morgan and 1 patient (9%) underwent excision of thrombosed external hemorrhoids. 73% of patients did not require surgery., Conclusions: Manual reduction of the prolapsed piles outside the anus decreased pain immediately and it also allows postponement of surgery or any other treatment.

West Nile virus (WNV) is a mosquito-transmitted Flavivirus belonging to the Japanese encephalitis antigenic complex of the Flaviviridae family. Its spread in the Mediterranean basin and the Balkans poses a significant risk to human health and forces public health officials to constantly monitor the virus transmission to ensure prompt application of preventive measures. In this context, predictive tools indicating the areas and periods at major risk of WNV transmission are of paramount importance. Spatial analysis approaches, which use environmental and climatic variables to find suitable habitats for WNV spread, can enhance predictive techniques. Using the Mahalanobis Distance statistic, areas ecologically most suitable for sustaining WNV transmission were identified in the Mediterranean basin and Central Europe. About 270 human and equine clinical cases notified in Italy, Greece, Portugal, Morocco, and Tunisia, between 2008 and 2012, have been considered. The environmental variables included in the model were altitude, slope, night time Land Surface Temperature, Normalized Difference Vegetation Index, Enhanced Vegetation Index, and daily temperature range. Seasonality of mosquito population has been modelled and included in the analyses to produce monthly maps of suitable areas for West Nile Disease. Between May and July, the most suitable areas are located in Tunisia, Libya, Egypt, and North Cyprus. Summer/Autumn months, particularly between August and October, characterize the suitability in Italy, France, Spain, the Balkan countries, Morocco, North Tunisia, the Mediterranean coast of Africa, and the Middle East. The persistence of suitable conditions in December is confined to the coastal areas of Morocco, Tunisia, Libya, Egypt, and Israel.