Increased number of children in households may protect against inflammatory bowel disease.

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.

Haemophilia care in Europe - A survey of 37 countries.

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.

Development of a forecasting model for brucellosis spreading in the Italian cattle trade network aimed to prioritise the field interventions.

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.

Mucosal Healing in Clinical Practice: A Single-Center Pediatric IBD Experience.

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.

A Transitional Model for the Evaluation of West Nile Virus Transmission in Italy.

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.

Interleukin-4 rapidly down-modulates the macrophage colony-stimulating factor receptor in murine macrophages.

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.

The use of a web-based interactive geographical information system for the surveillance of bluetongue in Italy.

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.

Novel ligands specific for mitochondrial benzodiazepine receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives. Synthesis, structure-activity relationships, and molecular modeling studies.

A novel class of ligands specific for MBR receptors has been identified: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives. The majority of newly synthesized esters 37-64 as well as some intermediate ketones showed micro- or nanomolar affinity for [3H]PK 11195 binding inhibition. A SAR study on 42 compounds and a molecular modeling approach led to a preliminary structural selectivity profile: the 6,7-double bond, the carbamoyloxy, alcanoyloxy, and mesyloxy side chains at the 7-position, and the prospective chloro substitution at the 4-position seemed to be the most important structural features improving affinity. Therefore, 7-[(dimethylcarbamoyl)oxy]- and 7-acetoxy-4-chloro-6-phenylpyrrolo[2,1-d][1,5]benzothiazepine (43 and 57) were synthesized. With 7-[(dimethylcarbamoyl)oxy]-6-(p-methoxyphenyl)pyrrolo[2,1- d][1,5]benzothiazepine (65), these were the most promising compounds with IC50s of respectively 9, 8, and 9 nM, under conditions where PK 11195 had an IC50 of 2 nM.

Picomolar quantitation of free sulfite in foods by means of [57Co]hydroxocobalamin and radiometric chromatography of [57Co]sulfitocobalamin. Method, applications and significance of coexisting sulfides.

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.

Synthesis of 4-quinolylazide derivatives and evaluation of their antitumor and antimicrobial activity.

Synthesis and pharmacological evaluation of a series of 4-quinolylazide derivatives are reported. These were screened against P388 lymphocitic leukemia in mice, but they resulted inactive. All the compounds were also tested for their antimicrobial activity against gram-positive, gram-negative strains and fungi; only three derivatives exhibited poor activity.

New quinoline derivatives: synthesis and evaluation for antiinflammatory and analgesic properties--Note II.

The synthesis of new halogenated series of 4-anilinoquinoline-3-carboxylic acids, N-[3-carboxyquinolyl(4)]anthranilic acids and their corresponding esters is reported. These have been obtained by reacting 4-chloro-3-carbethoxy-quinolines with variously substituted anilines and methyl anthranilate respectively. The synthesized compounds were tested for antiinflammatory and analgesic activities; some of them showed a good analgesic activity, sometimes higher than that of indomethacin, used as reference drug.

New 1-[quinolyl(4)]-1,2,3-triazoles: synthesis and evaluation of antiinflammatory and analgesic properties. II.

Several 1-[quinolyl(4)]-1,2,3-triazoles were synthesized by 1,3-dipolar cycloaddition of 4-azidoquinolines with activated methylene compounds. The synthesized compounds, tested for antiinflammatory and analgesic activities, resulted moderately active as antiinflammatories, but with a very interesting analgesic activity, sometimes higher than that of indomethacin, used as reference drug. Some of the triazole derivatives were evaluated also as antimicrobial, but none of them exhibited activity.

Chelating agents as potential antitumorals: alpha-(N)-heterocyclic hydrazones and bis-alpha-(N)-heterocyclic hydrazones.

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.

New quinoline derivatives: synthesis and evaluation for antiinflammatory and analgesic properties--Note I.

New 4-anilinoquinoline-3-carboxylic acids, N-[3-carboxyquinolyl (4)]anthranilic acids and their corresponding esters were synthetized by reacting 4-chloro-3-carbethoxyquinolines with substituted anilines and methyl anthranilate respectively. All the compounds were tested for antiinflammatory and analgesic activities. Some derivatives showed a significant antiinflammatory activity comparable to that of indomethacin.

Synthesis and pharmacological activity of 1,2,4-triazolo[4,3-a]quinolines.

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.

New 1-[quinolyl(4)]-1,2,3-triazoles: synthesis and evaluation of antiinflammatory and analgesic properties. I.

The synthesis of new 1-[quinolyl(4)]-1,2,3-triazoles is reported. These have been obtained by reacting 4-azidoquinolines with ethyl p-nitrobenzoylacetate. The synthesized compounds, tested for antiinflammatory and analgesic activities, results moderately active as antiinflammatories, but with a very interesting analgesic activity, sometimes higher than that of indomethacin, used as reference drug.

Pyrazolo[4,3-c]quinolines, synthesis and specific inhibition of benzodiazepine receptor binding. Note II.

Two new series of 2-arylpyrazolo[4,3-c]quinolin-3-ones (6,8-difluoro- and 7,9-dichloro-derivatives) have been synthesized and tested for their ability to displace [3H]flunitrazepam from rat brain membranes. Several compounds possess comparable and sometimes higher affinity for central benzodiazepine receptors than that of diazepam. Some selected compounds were also tested in vivo in the anti-pentylenetetrazol test; some anticonvulsant activity resulted for the 6,8-difluoroderivatives only.

Pyrazolo [4,3-c] quinolines synthesis and specific inhibition of benzodiazepine receptor binding (Note I).

A series of 2-arylpyrazolo[4,3-c] quinolin-3-one derivatives, bearing different substituents in the two aromatic rings, were prepared and tested for their ability to displace [3H] flunitrazepam from rat brain membranes. Some compounds have shown an affinity for receptors comparable and sometimes higher than that of CGS series.

Quinolinehydrazones as inhibitors of retroviral reverse transcriptase.

The inhibitory activity of a series of 2- and 4-quinolinehydrazones on retroviral reverse transcriptase has been studied on enzymes from M-MuLV, RAV-2, and on a crude lysate of HIV-1, assuming the first two enzymes as potential models of the third. The highest activity is mainly found in lipophilic, water soluble 4-quinolinehydrazones. The inhibitory activity of these compounds decreases in changing from the M-MuLV to the RAV-2, and HIV-1 enzymes, in this order.

An integrated web system to support veterinary activities in Italy for the management of information in epidemic emergencies.

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.