An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4+ T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Barriers to health care services for migrants living with HIV in Spain

BACKGROUND: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. METHODS: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. RESULTS: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2–7.2]) and women (OR: 10.5 [95%CI: 3.1–34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9–5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2–3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3–30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3–25.1]) were more likely to report barriers. CONCLUSION: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints

Complete plastome phylogeny and an update on cox1 intron evolution of Hyoscyameae (Solanaceae)

Within the family Solanaceae, the tribe Hyoscyameae comprises eight genera distributed across Eurasia. Despite a few attempts to understand the relationships within this tribe, the affiliations among most genera remain unresolved. Recently, complete chloroplast genomes from several species of Hyoscyameae were published, enabling phylogenomic inferences. We sequenced the plastome of Scopolia carniolica, the second species of the genus to be reported. Genomic comparisons across the tribe revealed identical gene content and small differences in genome length. Phylogenetic analyses confirmed that Atropa is an early-diverging lineage sister to the rest of the tribe, resolved as two clades. One includes well-supported relationships between Przewalskia, Physochlaina, and Scopolia, and these three genera are sister to Atropanthe. This clade is sister to a second clade composed of Hyoscyamus and Anisodus. The strongly supported phylogenetic affiliations of Atropanthe, Anisodus, and Hyoscyamus represent the major advancements as previous studies were not able to resolve these relationships. Interestingly, the genus Scopolia is paraphyletic in respect to Physochlaina, based on ITS2 sequences. Finally, the evolution of the mitochondrial cox1 intron is reinterpreted. Two independent horizontal acquisitions are inferred, one in the ancestor of Przewalskia, Physochlaina, and S. japonica and another in Hyoscyamus, with no intron losses

Atenção básica e dinâmica urbana nos grandes municípios paulistas, Brasil Primary health care and urban dynamics in large cities in São Paulo State, Brazil

Os Estudos de Linha de Base do Projeto de Expansão e Consolidação do Saúde da Família construíram indicadores e modelos de atenção básica para os 62 municípios paulistas com mais de 100 mil habitantes, e apontaram uma diversidade de comportamento destes indicadores e modelos em relação às diferentes dinâmicas urbanas do estado. Nesse sentido, houve a necessidade de realizar uma reflexão sobre saúde e uso urbano do território. O principal objetivo desta reflexão foi compreender melhor sobre como a dinâmica urbana tem influência no perfil, na organização e no funcionamento do sistema de saúde. A partir daí, foi possível extrair algumas hipóteses e discussões sobre como a urbanização paulista impõe desafios à expansão e consolidação da atenção básica e do Programa Saúde da Família nos municípios estudados.<br>The Baseline Studies on the Project for Expansion and Consolidation of the Family Health Strategy created primary health care indicators and models for the 62 municipalities with more than 100,000 inhabitants in São Paulo State, Brazil, and identified varying patterns for these indicators and models in relation to different urban dynamics in the State. The studies showed the need to reflect on health in relation to urban land use. The main objective was to gain a better understanding of how urban dynamics influence the health system's profile, organization, and operation, based on which it was possible to extract some hypotheses and discussions regarding how urbanization in São Paulo State creates challenges for the expansion and consolidation of primary health care and the Family Health Program in these municipalities