Newcastle Disease Virus in Madagascar: Identification of an Original Genotype Possibly Deriving from a Died Out Ancestor of Genotype IV

In Madagascar, Newcastle disease (ND) has become enzootic after the first documented epizootics in 1946, with recurrent annual outbreaks causing mortality up to 40%. Four ND viruses recently isolated in Madagascar were genotypically and pathotypically characterised. By phylogenetic inference based on the F and HN genes, and also full-genome sequence analyses, the NDV Malagasy isolates form a cluster distant enough to constitute a new genotype hereby proposed as genotype XI. This new genotype is presumably deriving from an ancestor close to genotype IV introduced in the island probably more than 50 years ago. Our data show also that all the previously described neutralising epitopes are conserved between Malagasy and vaccine strains. However, the potential implication in vaccination failures of specific amino acid substitutions predominantly found on surface-exposed epitopes of F and HN proteins is discussed

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The prevalence and determinants of undiagnosed and diagnosed type 2 diabetes in middle-aged irish adults.

BACKGROUND: The prevalence of type 2 diabetes within the Republic of Ireland is poorly defined, although a recent report suggested 135,000 cases in adults aged 45+, with approximately one-third of these undiagnosed. This study aims to assess the prevalence of undiagnosed and diagnosed diabetes in middle-aged adults, and compare features related to either condition, in order to investigate why certain individuals remain undetected. METHODS: This was a cross-sectional study involving a sample of 2,047 men and women, aged between 50-69 years, randomly selected from a large primary care centre. Univariate logistic regression was used to explore socio-economic, metabolic and other health related variable associations with undiagnosed or diagnosed diabetes. A final multivariate analysis was used to determine odds ratios and 95% confidence intervals for having undiagnosed compared to diagnosed diabetes, adjusted for gender, age and significant covariates determined from univariate models. PRINCIPLE FINDINGS: The total prevalence of diabetes was 8.5% (95% CI: 7.4%-8.8%); 72 subjects (3.5%) had undiagnosed diabetes (95% CI: 2.8%-4.4%) and 102 subjects (5.0%) had diagnosed diabetes (95% CI: 4.1%-6.0%). Obesity, dyslipidaemia, and family history of diabetes were positively associated with both undiagnosed and diagnosed type 2 diabetes. Compared with diagnosed subjects, study participants with undiagnosed diabetes were significantly more likely to have low levels of physical activity and were less likely to be on treatment for diabetes-related conditions or to have private medical insurance. CONCLUSIONS: The prevalence of diabetes within the Cork and Kerry Diabetes and Heart Disease Study is comparable to recent estimates from the Slán National Health and Lifestyle Survey, a study which was nationally representative of the general population. A considerable proportion of diabetes cases were undiagnosed (41%), emphasising the need for more effective detection strategies and equitable access to primary healthcare

Ocorrência e fatores de risco da infecção por Toxoplasma gondii em suínos criados e abatidos na região do Triângulo Mineiro, Minas Gerais, Brasil

Submitted by Sandra Infurna ([email protected]) on 2018-02-06T12:01:41Z No. of bitstreams: 1 mariaregina_amendoeira_etal_IOC_2017.pdf: 917033 bytes, checksum: 74384c0b1588811f16d472eb6cf3a6a7 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-02-06T12:14:56Z (GMT) No. of bitstreams: 1 mariaregina_amendoeira_etal_IOC_2017.pdf: 917033 bytes, checksum: 74384c0b1588811f16d472eb6cf3a6a7 (MD5)Made available in DSpace on 2018-02-06T12:14:56Z (GMT). No. of bitstreams: 1 mariaregina_amendoeira_etal_IOC_2017.pdf: 917033 bytes, checksum: 74384c0b1588811f16d472eb6cf3a6a7 (MD5) Previous issue date: 2017Universidade Federal Fluminense. Departamento de Microbiologia e Parasitologia. Laboratório de Parasitologia. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose e outras Protozoonoses. Rio de Janeiro, RJ. Brasil.Universidade Federal de Uberlândia. Faculdade de Medicina Veterinária. Uberlândia, MG, Brasil.Sem afiliaçãoUniversidade Federal Fluminense. Departamento de Microbiologia e Parasitologia. Laboratório de Parasitologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Departamento de Microbiologia e Parasitologia. Laboratório de Parasitologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Departamento de Microbiologia e Parasitologia. Laboratório de Parasitologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Departamento de Microbiologia e Parasitologia. Laboratório de Parasitologia. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose e outras Protozoonoses. Rio de Janeiro, RJ. Brasil.The Triângulo Mineiro region from Minas Gerais state, is an important meat-exporting region of Brazil and data about Toxoplasma gondii infection in pigs raised and slaughtered in this area are scarce. Therefore, the aim of this study was to evaluate the occurrence of T. gondii in swine and establish the risk factors associated with the infection. Samples were collected from 600 pigs raised under intensive system in farms located at three different counties (Carmo do Paranaíba, Patrocínio and Perdizes). The samples were submitted to indirect hemagglutination antibody test with dilution of 1:32 and to indirect immunofluorescence antibody test with a cutoff of 1:64. The occurrence of positive pig was 3.3% (n=20) and 51.8% (n=311) respectively. A significant difference was observed between toxoplasmatic infection and factors such as lineage, animal origin, size of the farm, collective raising with others species, presence of rodents and type of water offered (p≤0.05). There was no difference between gender and the farm goals. The results demonstrated an occurrence of anti-T. gondii antibodies higher than expected for intensive pig raising system on the studied area, which could indicate a possible sanitary management problem on the studied proprieties. Improvements on the raising techniques are necessary to reduce T. gondii infection sources

Odds ratios (95% CI) of having undiagnosed or diagnosed type 2 diabetes compared to no diabetes – multivariate logistic regression adjusted for gender, age and all significant covariates.

1<p>Model excludes subjects with diagnosed T2DM. Final model covariates entered in order: dyslipidaemia, BMI</p><p>category, physical activity, health insurance, on Rx for cholesterol, family history of T2DM, gender and age.</p>2<p>Model excludes subjects with undiagnosed T2DM. Final model covariates entered in order: family history of T2DM,</p><p>on Rx for hypertension, BMI category, on Rx for cholesterol, CVD, dyslipidaemia, alcohol use, gender and age.</p>3<p>Dyslipidaemia: TAG≥1.7 and HDL-C: <1.03 (MALES) <1.29 (FEMALES).</p

Univariate odds ratios (95% CI) of having undiagnosed compared to diagnosed type 2 diabetes.¹

1<p>Mean and ± SD are shown for continuous variables. TAG is shown as a median (interquartile range). Numbers and % (in brackets) for categorical variables will vary in different analyses as some variables have missing values.</p>2<p>HDL-C: <1.03 (MALES) <1.29 (FEMALES).</p>3<p>Dyslipidaemia: TAG≥1.7 and HDL-C: <1.03 (MALES) <1.29 (FEMALES).</p>4<p>Hypertension: SBP≥140 and/or DBP≥90.</p