Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas' disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-g-producing T cells.Universidade Federal de São Paulo (UNIFESP)Instituto Dante Pazzanese de Cardiologia do Estado de São PauloUNIFESPSciEL

Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?

In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines

Variação sazonal nas hospitalizações por insuficiência cardíaca em Niterói, RJ

O objetivo do estudo foi descrever a sazonalidade das hospitalizações por insuficiência cardíaca em climas tropicais, aspecto já conhecido em climas frios. Aplicou-se o Modelo Sazonal Auto-Regressivo Integrado de Médias Móveis a uma série histórica de 6.596 hospitalizações por insuficiência cardíaca no município de Niterói, RJ, de 1996 a 2004, obtida do Banco de Dados do Sistema Único de Saúde. A variação sazonal padrão foi obtida por meio da filtragem e cálculo da média-móvel dos dados. O menor número de hospitalizações por ano foi 507 (1997) e o maior 849 (2002); e por mês 419 (dezembro) e 681 (outrubro), respectivamente. Foram observados picos de internação no outono e inverno. Ainda que fraca, a sazonalidade observada mostra que uma pequena variação pode levar ao aumento de hospitalizações.El objetivo del estudio fue describir la estacionalidad de las hospitalizaciones por insuficiencia cardiaca en climas tropicales, aspecto ya conocido en climas fríos. Se aplicó el Modelo Estacional Auto-Regresivo Integrado de Promedios Móviles a una serie histórica de 6.596 hospitalizaciones por insuficiencia cardiaca en el municipio de Niteroi, Sureste de Brasil, de 1996 a 2004, obtenida del Banco de Datos del Sistema Único de Salud. La variación estacional estándar fue obtenida por medio de la filtración y cálculo del promedio-móvil de los datos. El menor número de hospitalizaciones por año fue 507 (1997) y el mayor 849 (2002); e por mes 419 (diciembre) y 681 (octubre), respectivamente. Se observaron picos de internación en otoño e invierno. A pesar de que fue débil, la estacionalidad observada muestra que una pequeña variación puede llevar al aumento de hospitalizaciones.The objective of the study was to describe seasonality of hospitalizations for heart failure in tropical climate as it has been described in cold climates. Seasonal Auto-regressive Integrated Moving-Average model was applied to time-series data of heart failure hospitalizations between 1996 and 2004 in Niteroi (Southeastern Brazil), collected from the Brazilian National Health Service Database. The standard seasonal variation was obtained by means of moving-average filtering and averaging data. The lowest and the highest annual hospital admissions were 507 (1997) and 849 (2002), respectively; the lowest and the highest monthly rates were 419 (December) and 681 (October), respectively. Peak admission rates were seen during the fall and winter. Although weak, the seasonality observed indicates that slight variations result in increased hospitalizations for heart failure

Antithrombotic Treatment in Transcatheter Aortic Valve Implantation Insights for Cerebrovascular and Bleeding Events

Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic alternative for patients with symptomatic aortic stenosis at high or prohibitive surgical risk. However, patients undergoing TAVI are also at high risk for both bleeding and stroke complications, and specific mechanical aspects of the procedure itself can increase the risk of these complications. The mechanisms of periprocedural bleeding complications seem to relate mainly to vascular/access site complications (related to the use of large catheters in a very old and frail elderly population), whereas the pathophysiology of cerebrovascular events remains largely unknown. Further, although mechanical complications, especially the interaction between the valve prosthesis and the native aortic valve, may play a major role in events that occur during TAVI, post-procedural events might also be related to a prothrombotic environment or state generated by the implanted valve, the occurrence of atrial arrhythmias, and associated comorbidities. Antithrombotic therapy in the setting of TAVI has been empirically determined, and unfractionated heparin during the procedure followed by dual antiplatelet therapy with aspirin (indefinitely) and clopidogrel (1 to 6 months) is the most commonly recommended treatment. However, bleeding and cerebrovascular events are common; these may be modifiable with optimization of periprocedural and post-procedural pharmacology. Further, as the field of antiplatelet and anticoagulant therapy evolves, potential drug combinations will multiply, introducing variability in treatment. Randomized trials are the best path forward to determine the balance between the efficacy and risks of antithrombotic treatment in this high risk-population

Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.

BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective

Potential application for antimicrobial and antileukemic therapy of a flavonoid-rich fraction of Camellia sinensis

The antimicrobial and antileukemic effect of a purified fraction of flavonoids from the leaves of Camellia sinensis was evaluated. An extraction yield of 9.77 mg.g-1 total flavonoids was recovered through a pressurized liquid extraction associated with solid-phase extraction. This fraction was tested against pathogenic microorganisms (Staphylococcus, Salmonella, and Enterococcus), considering the minimum inhibitory concentration. In addition, the human monocyte cell line THP-1, derived from a patient with acute monocytic leukemia, was used for the antitumor assay. The results show that the flavonoid-rich fraction obtained by coupling a Pressurized Liquids Extraction in-line with a Solid Phase Extraction (PLE-SPE) has a high antimicrobial effect and resulted in cell cycle blockage G0 / G1, increased DNA fragmentation, and altered leukemic cell morphology. These results suggest that a flavonoid-rich fraction obtained from Camellia sinensis can be applied as potential adjuvants in chemotherapy treatment to mitigate the side effects caused by chemotherapy or even as a supplement to cancer therapy9 página

MINDMAP : establishing an integrated database infrastructure for research in ageing, mental well-being, and the urban environment

Background: Urbanization and ageing have important implications for public mental health and well-being. Cities pose major challenges for older citizens, but also offer opportunities to develop, test, and implement policies, services, infrastructure, and interventions that promote mental well-being. The MINDMAP project aims to identify the opportunities and challenges posed by urban environmental characteristics for the promotion and management of mental well-being and cognitive function of older individuals. Methods: MINDMAP aims to achieve its research objectives by bringing together longitudinal studies from 11 countries covering over 35 cities linked to databases of area-level environmental exposures and social and urban policy indicators. The infrastructure supporting integration of this data will allow multiple MINDMAP investigators to safely and remotely co-analyse individual-level and area-level data. Individual-level data is derived from baseline and follow-up measurements of ten participating cohort studies and provides information on mental well-being outcomes, sociodemographic variables, health behaviour characteristics, social factors, measures of frailty, physical function indicators, and chronic conditions, as well as blood derived clinical biochemistry-based biomarkers and genetic biomarkers. Area-level information on physical environment characteristics (e.g. green spaces, transportation), socioeconomic and sociodemographic characteristics (e.g. neighbourhood income, residential segregation, residential density), and social environment characteristics (e.g. social cohesion, criminality) and national and urban social policies is derived from publically available sources such as geoportals and administrative databases. The linkage, harmonization, and analysis of data from different sources are being carried out using piloted tools to optimize the validity of the research results and transparency of the methodology. Discussion: MINDMAP is a novel research collaboration that is combining population-based cohort data with publicly available datasets not typically used for ageing and mental well-being research. Integration of various data sources and observational units into a single platform will help to explain the differences in ageing-related mental and cognitive disorders both within as well as between cities in Europe, the US, Canada, and Russia and to assess the causal pathways and interactions between the urban environment and the individual determinants of mental well-being and cognitive ageing in older adults.Peer reviewe