RESUMEN

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) around the world has coincided with a wide array of environmental and epidemiologic changes. The relationship between IBD incidence and household or family size decline, however, has not been examined before. Our background epidemiological analyses suggested an inverse association between household size and IBD incidence. We aimed to examine this further in a murine model. METHODS: We designed a unique two-generation cohousing model of family size and IBD susceptibility in C57BL/6J mice. Serial fecal microbiomes during cohousing were examined by high-throughput 16S rRNA sequencing. After cohousing for 10 days, mice were exposed to dextran sulfate sodium (DSS) to induce acute colitis. Body weight as a significant correlate of colitis severity was measured. RESULTS: Mice in a large household arrangement demonstrated less weight loss than mice in the small household arrangement in the DSS model. Age- and housing-dependent microbiome shifts were found. CONCLUSIONS: Larger households may be protective against intestinal inflammation through intergenerational microbiome modulation. Our observations may set the foundation for age-dependent, microbiome-directed future prevention against IBD. IMPACT: Epidemiological analyses in this study suggested that IBD incidence may inversely correlate with household size (an indicator of family size/children per family), which has not been examined before. A uniquely designed two-generation cohousing model of family size and IBD susceptibility in mice supported our epidemiologic observations. Microbiome changes in our cohousing model may set the foundation for age-dependent, microbiome-directed prevention against IBD.

Asunto(s)

RESUMEN

INTRODUCTION: The European Haemophilia Consortium (EHC) is an international non-profit organization representing 45 national patients' organizations in Europe. Every 3 years, the EHC circulates a survey to its national member organizations to assess the state of haemophilia care. AIM: The purpose of this exercise is to ascertain information about the organization of haemophilia care and treatment availability at national levels. Furthermore, the survey provides a basis from which the EHC are able to monitor the unmet need and stability of care/treatment access in the individual member countries. PATIENTS AND METHODS: Surveys are distributed to EHC member organizations in English and Russian. Patient organizations are encouraged to share the survey with local clinicians to ensure accuracy of responses. The data collected are in part consistent to provide a longitudinal overview for treatment access, but topical items are included such as ageing. Subsequently, completed surveys are transposed into a database for analysis and reporting. RESULTS: Thirty-seven responses were received from the 45 countries approached, representing an 82% response rate from members. Findings suggest increased access to treatment and some improvement in certain areas of care. However, access to treatment has declined or remained largely unchanged in some countries. CONCLUSION: The survey has been a successful exercise in enabling a greater understanding of the current Haemophilia care landscape across Europe. However, there remain unmet needs in various aspects of patient care, and specific examples include psychosocial care and general preparedness for an ageing haemophilia population.

Asunto(s)

RESUMEN

Brucellosis caused by Brucella abortus is an important zoonosis that constitutes a serious hazard to public health. Prevention of human brucellosis depends on the control of the disease in animals. Livestock movement data represent a valuable source of information to understand the pattern of contacts between holdings, which may determine the inter-herds and intra-herd spread of the disease. The manuscript addresses the use of computational epidemic models rooted in the knowledge of cattle trade network to assess the probabilities of brucellosis spread and to design control strategies. Three different spread network-based models were proposed: the DFC (Disease Flow Centrality) model based only on temporal cattle network structure and unrelated to the epidemiological disease parameters; a deterministic SIR (Susceptible-Infectious-Recovered) model; a stochastic SEIR (Susceptible-Exposed-Infectious-Recovered) model in which epidemiological and demographic within-farm aspects were also modelled. Containment strategies based on farms centrality in the cattle network were tested and discussed. All three models started from the identification of the entire sub-network originated from an infected farm, up to the fifth order of contacts. Their performances were based on data collected in Sicily in the framework of the national eradication plan of brucellosis in 2009. Results show that the proposed methods improves the efficacy and efficiency of the tracing activities in comparison to the procedure currently adopted by the veterinary services in the brucellosis control, in Italy. An overall assessment shows that the SIR model is the most suitable for the practical needs of the veterinary services, being the one with the highest sensitivity and the shortest computation time.

Asunto(s)

RESUMEN

BACKGROUND: Mucosal healing (MH) is associated with improved clinical outcomes in patients with Crohn's disease (CD) and ulcerative colitis (UC). MH as a target for treatment has been suggested, although there is little pediatric data. The goal of this study was to evaluate MH in clinical practice in pediatric patients with inflammatory bowel disease in clinical remission. METHODS: A retrospective review of electronic health record data was performed on all patients with CD or UC who underwent at least 2 colonoscopies from 2010 through 2016. Only patients in clinical remission undergoing a scope for MH were included in our study. The incidence of MH and histologic healing (HH) was analyzed, along with cumulative rates of MH in each group. MH was defined by both physician assessment of MH and an endoscopic score of zero for CD and UC. RESULTS: A total of 76 patients with CD and 28 patients with UC underwent at least one MH scope while in clinical remission. Of the 76 patients with CD, 51 patients (67%) demonstrated MH by physician assessment, 34 patients (45%) demonstrated MH by a simple endoscopic score for CD of zero, and 35 patients (46%) demonstrated HH. Of the 28 patients with UC, 20 patients (71%) demonstrated MH by physician assessment, 10 patients (36%) demonstrated MH by a Mayo score of zero, and 10 patients (36%) demonstrated HH. Nineteen patients underwent a second MH scope and 11 (58%) demonstrated MH by physician assessment, 7 patients (37%) demonstrated MH by simple endoscopic score for CD or Mayo scores of zero, and 5 patients (26%) demonstrated HH. Of those patients with active disease, 21 of 25 patients with CD underwent escalation of therapy, whereas 8 of 8 patients with UC underwent escalation of therapy. Cumulative rates of MH when defined by physician assessment were 79% (60 of 76 patients) in CD and 79% (22 of 28 patients) in UC. CONCLUSIONS: MH is feasible in pediatric CD and UC, and rates of cumulative MH in pediatric patients are similar to previously published adult data. In children with inflammatory bowel disease in clinical remission, approximately one-third demonstrate active disease at endoscopy.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

The management of public health emergencies is improved by quick, exhaustive and standardized flow of data on disease outbreaks, by using specific tools for data collection, registration and analysis. In this context, the National Information System for the Notification of Outbreaks of Animal Diseases (SIMAN) has been developed in Italy to collect and share data on the notifications of outbreaks of animal diseases. SIMAN is connected through web services to the national database of animals and holdings (BDN) and has been integrated with tools for the management of epidemic emergencies. The website has been updated with a section dedicated to the contingency planning in case of epidemic emergency. EpiTrace is one such useful tool also integrated in the BDN and based on the Social Network Analysis (SNA) and on network epidemiological models. This tool gives the possibility of assessing the risk associated to holdings and animals on the basis of their trade, in order to support the veterinary services in tracing back and forward the animals in case of outbreaks of infectious diseases.

Asunto(s)

RESUMEN

During the recent severe outbreaks of bluetongue (BT) in the Mediterranean Basin, the BT virus (BTV) spread beyond its historical limits into the Balkan region. One of the primary impacts of BT is the cessation in livestock trade which can have severe economic and social consequences. The authors briefly describe the development of the collaborative East-BTnet programme which aims to assist all affected and at-risk Balkan states and adjoining countries in the management of BT, and in the development of individual national surveillance systems. The beneficiary countries involved, and led by the World organisation for animal health (Office International des Epizooties) Collaborating Centre for veterinary training, epidemiology, food safety and animal welfare of the Istituto Zooprofilattico dell'Abruzzo e del Molise 'G. Caporale' in collaboration with the Institute for the Protection and the Security of the Citizen, the European Commission Joint Research Centre (IPSC-JRC), were Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Cyprus, the Former Yugoslavia Republic of Macedonia, Kosovo, Malta, Romania, Serbia and Montenegro, Slovenia and Turkey. A regional web-based surveillance network is a valuable tool for controlling and managing transboundary animal diseases such as BT. Its implementation in the Balkan region and in adjoining areas of south-eastern Europe is described and discussed.

RESUMEN

Bluetongue (BT) is an infectious, non-contagious, arthropod-borne disease transmitted by biting midges. When BT spread throughout the Balkans (affecting Albania, Bosnia-Herzegovina, Bulgaria, Croatia, the Former Yugoslav Republic of Macedonia and Serbia and Montenegro), it caused serious concerns for veterinary authorities in all countries in the eastern Mediterranean. In 2003-2004 a web-based BT geographic information system network was developed and implemented to provide veterinary services with a tool to manage and analyse data on the disease and to exchange information. The system was centralised to ensure there was a common epidemiological surveillance strategy. Spatial and alphanumerical data on the disease were organised in a single relational geographic database. The system was equipped with a number of applications for the display of dynamic maps and data information via the web, with multi-user access for simultaneous queries from additional users.

RESUMEN

Consequent upon the bovine spongiform encephalopathy (BSE) crisis, the European Union (EU) Commission enacted various decisions, which demanded that all bovine animals over 30 months of age should be examined by one of the approved rapid tests when slaughtered for human consumption. All cattle over 24 months of age subject to 'special emergency slaughtering' or died on the farm or in transit or suspect of BSE infection should also be examined by one of the approved rapid tests. According to a specific commission decision, Sweden and Finland were to test only a sample of bovine animals over 30 months of age subject to normal slaughter. Testing commenced on 1 January 2001. The authors evaluate the results of more than 5 million tests performed in the second semester 2001 from across the EU. The prevalence of BSE in the risk categories considered (emergency slaughter, fallen stock and healthy slaughtered), and the probability distribution of true-positive, false-positive and false-negative results are estimated by second-order Bayesian analysis. The results of the validation of tests performed in the EU are also considered by estimation of the probability distribution of their sensitivity and specificity. The prevalence of infection estimated in the cattle population of each EU country is compared against the criteria given in the OIE Terrestrial Animal Health Code and is also used to evaluate the consistency of the results of EU Geographical BSE Risk with the actual infection levels in the countries. Finally, the capability of the two current approaches to BSE surveillance (i.e. the testing of all slaughtered and dead cattle as applied in the EU and a surveillance system targeted at animals in risk categories only) to detect the infection in a given population are discussed.

Asunto(s)

RESUMEN

Since 2000 Italy has experienced five epidemics of bluetongue, an arthropod-borne disease that affects primarily sheep and asymptomatically cattle, goats and wildlife ruminants. In four years the disease spread through Southern and Central Italy, involving 14 Italian regions out of 20. To control the disease, the Ministry of Health established a surveillance system that included clinical, entomological and serological surveillance elements. The National Reference Centre for Veterinary Epidemiology--Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise 'G. Caporale'--developed a Web-based National Information System (NIS) and a Geographical Information System (GIS)to collect and manage data from Veterinary Services across Italy. The system was designed to gather and spread information in order to support the management of control activities and to provide an early warning system. Surveillance data are displayed to the user in different ways: reports, tables and interactive maps.

Asunto(s)

RESUMEN

The occurrence of bluetongue virus (BTV) in areas in which intensive animal production is practised and where there is extensive movement of animals may have a substantial impact on both animal trade and husbandry. This situation occurred in Italy after the detection of bluetongue (BT) in August 2000. In such situations, surveillance can be used to delineate with precision those areas in which the virus is circulating and, consequently, to enforce the appropriate animal movement restrictions. Furthermore, surveillance can provide the data required to assess the risk associated with animal movement and trade. A structured surveillance system for the detection of BTV has been in place in Italy since August 2001. The system is based on the periodical testing of unvaccinated sentinel cattle that are uniformly scattered throughout Italy in a grid of 400 km(2) cells. The initial number of sentinel sites and sentinel animals, together with the width of the restricted area generated by the finding of a single seroconversion in a sentinel animal, were based on conservative criteria. Animal movement was restricted in a 20 km radius buffer zone around any positive serological result. This buffer area extends about 1,257 km(2), equivalent to the area of three grid cells. After the commencement of the BT vaccination campaign in Italy, the sentinel surveillance system was the only way in which the effectiveness of vaccination and the incidence of infection in the non-immunised strata of ruminant animals could be estimated. Data collected over two years was used to assess the risks posed by the adoption of less conservative criteria for the delineation of infected areas and by the progressive relaxation of movement restrictions of vaccinated animals. In regard to the delineation of restricted areas, a new approach was tested and validated in the field, based on a Bayesian analysis of the positive and negative results obtained by the testing of sentinel animals from defined regions. For the risks related to animal movement, the surveillance data was used in risk assessment analyses to address the movement of slaughter and breeding animals from vaccinated/infected and surrounding areas to free areas. These risk assessments led to an amendment of the relevant European Union legislation. Finally, a Montecarlo simulation model was developed to simulate different sentinel system scenarios and to decrease the total number of sentinel animals and sites required by the surveillance system. The sentinel surveillance system was complemented by an entomological surveillance system based on the use of a number of permanent blacklight traps run weekly year-round and a number of mobile blacklight traps moved through the grid cells during the summer and autumn of each year. The aim of entomological surveillance was to define the maximum distribution of vectors and their seasonal population dynamics. Furthermore, the permanent trap system provides an early warning of the start of new epidemics. The data from the entomological surveillance system were also analysed to generate probability maps of the presence of the principal BTV vector (Culicoides imicola) and to define the geographical risk of BT on a nationwide basis, and to predict the geographical distribution and the short-term spread of C. imicola in Sardinia, using spatio-temporal data. The detection, since 2001, of BT outbreaks in the absence of C. imicola and the recent identification of BTV in midges of the Obsoletus Complex also stimulated investigations on other vector Culicoides, including C. obsoletus and C. pulicaris.

RESUMEN

A geographic information system (GIS) based on grids was developed by the National Reference Center for Veterinary Epidemiology at the Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise 'G. Caporale' (IZS) in Teramo to identify potential infectious sites for bluetongue (BT) disease in Italy. Geographical and climatic variables were used to build a spatial process model (SPM); the different layers were combined by sequential addition. The final grids (with a cell size of 0.0387 decimal degrees) were generated for each season of the year, and the suitability of each cell for the presence of C. imicola given a value ranking from 0 to 10. While this model more accurately predicts the presence of C. imicola in the Basilicata and Sicily regions, it still over-predicted its presence in the Puglia region. This could be due to the occurrence of calcareous soils which dominate the Puglia landscape. The present SPM is an additive model that assigns an equal weight to each variable. However, the results suggest the existence of hitherto unconsidered variables that significantly influence the prevalence of C. imicola. To reflect their importance, these variables should be assigned a higher weighting in future models. However, the decision in regard to precisely what this weighting should be depends on a very thorough knowledge of the ecology of C. imicola.

RESUMEN

A model was developed to classify the Italian territories in relation to their suitability to harbour populations of Culicoides imicola and, as a consequence, also able to sustain a bluetongue (BT) epidemic. Italy was subdivided into 3507 10 x 10 km cells. In 546 cells at least one collection was made. The cell was considered the unit for all subsequent analyses. Culicoides were collected using Onderstepoort-type blacklight traps. Some traps were operated weekly at chosen sites; the remainder were moved almost daily to new sites. Only the results obtained during the peak August-November period were used, to exclude bias caused by the seasonality of C. imicola. Climate data for the period 1999-2001 were obtained from 80 weather stations. Multiple logistic regression was performed using the presence or absence of C. imicola in a specific cell as the dependent variable. Annual means of daily values for minimum temperature and minimum relative humidity, and the mean altitude above sea level, were the independent variables. The probability of occurrence of C. imicola in each grid cell was used to create a prediction map for Italy. The model was able to correctly classify 77.5% of the 546 grid cells in which at least one collection had been made. Culicoides imicola was found frequently through much of Sardinia, in parts of southern Italy, and further north along the Tyrrhenian coast, but was absent from along most of the Adriatic coast, and the internal mainland, and from most of Sicily. Six detailed maps are provided. Also mapped are areas where the probability of the occurrence of C. imicola is lower than 5%. This identification of possible mountainous C. imicola-free areas in central Italy could facilitate safer animal trade and transhumance, even if BT infections in traded animals or moving stock, were to go undetected. Needless to say this depends upon no cool-adapted species of Culicoides being involved in the transmission of BT disease.

Asunto(s)

RESUMEN

Based upon synthetic and biochemical results, a novel and potent tacrine analogue and heterobivalent analogues of tacrine, were designed. The role played by the amino groups of homo- and heterobivalent ligands in the interaction with the peripheral and catalytic sites of AChE and BuChE were investigated. The syntheses of these materials together with the results of AChE/BuChE inhibition assays are detailed.

Asunto(s)

RESUMEN

A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H)-ones (PQ, 106 compounds), carrying appropriate substituents at the quinoline and N2-phenyl rings, were designed, prepared and tested as central benzodiazepine receptor ligands. Compounds with an affinity significantly higher than the parent compound CGS-8216 were obtained, the most active ligand showing a pIC50 = 10.35. Hansch and comparative molecular field analyses gave coherent results suggesting the main structural requirements of high receptor binding affinity. The possible formation of a three-centred hydrogen bond (HB) at the HB donor site H2, as a key interaction for high receptor binding affinity, was assessed by the calculation and comparison of the molecular electrostatic potentials of a series of selected ligands.

Asunto(s)

RESUMEN

The synthesis of a series of 1,2,4-triazolo[4,3-a]quinoline derivatives is described; their structures were assigned by 1H NMR and analytical data. The new compounds were tested in vivo for their antiinflammatory and analgesic activities, as well as for their ulcerogenic action. Some of the tested triazoles showed an analgesic activity in the acetic acid writhing test and antiinflammatory properties on carrageenan paw edema assay.

Asunto(s)

RESUMEN

The concentration dependent reaction of sulfite with 57Co-labeled hydroxocobalamin (OH57CoCbl) to produce a sulfitocobalamin (SO(3)57CoCbl) adduct served as a quantification strategy for foodborne sulfite residues freely extracted into pH 5.2, 0.05 M acetate buffer. SO(3)57CoCbl was then resolved using SP-Sephadex C-25 gel chromatography and its radiometric detection allowed calculation of a standard logit plot from which unknown sulfite concentrations could be determined. The sulfite detection range was 6.0 nM-0.3 pM with respective relative standard deviations of 4.4-29.4% for 50-microl samples. Individual incidences of foodborne sulfite intolerances provoked by L-cysteine or sulfite additive use in bakery products, which remained undetected using conventional sulfite analytical methods, underscored the quantitative value of the method. The analytical significance and occurrences of detectable sulfides coexisting with foodborne sulfite residues was also addressed.

Asunto(s)

RESUMEN

A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin- 3-(3H)-ones, carrying appropriate substituents at the quinoline and N2-phenyl rings, were prepared and tested as central benzodiazepine receptor ligands. Results from structure-affinity relationship studies were in full agreement with previously proposed pharmacophore models and, in addition, quantitative structure-activity analysis gave further significant insight into the main molecular determinants of high benzodiazepine receptor affinity. The intrinsic activity of some active ligands was also determined and preliminary discussed.

Asunto(s)

RESUMEN

A number of pyruvic acid and methylpyruvate alpha-(N)-heterocyclic hydrazones has been synthesized. Bis-heterocyclic hydrazones were obtained from reaction with pyruvic carboxaldehyde. Some complexes of Ni(II) were prepared and characterized as neutral complexes. All these compounds have been evaluated for cytotoxicity against P388 and HL-60 leukemia.

Asunto(s)

RESUMEN

The activation of macrophages interferes with their response to macrophage colony-stimulating factor (M-CSF), the main growth and differentiation factor for mononuclear phagocytes. We tested the rapid effects of interleukin-4 (IL-4), the alternative macrophage activator produced by Th2 helper lymphocytes, on the receptor for M-CSF (M-CSFR) expressed on the cell surface of murine macrophages. IL4 rapidly down-modulated M-CSFR in a dose-dependent fashion. This effect was unique to IL-4 among a number of Th2-produced cytokines, none of which, with the exception of IL4 itself, is able to activate macrophages. The down-modulation of M-CSFR by IL4 was partially prevented by the inhibition of the activity of phospholipase C or protein kinase C. The data are consistent with the hypothesis that the down-modulation of M-CSFR is a property common to, and exclusive of, macrophage activators, and is driven by different activators via a common mechanism.

Asunto(s)