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A recombinant multi-antigen vaccine formulation containing Babesia bovis merozoite surface antigens MSA-2a1, MSA-2b and MSA-2c elicits invasion-inhibitory antibodies and IFN-γ producing cells
No full textAbstract
Background
Babesia bovis is a tick-transmitted protozoan hemoparasite and the causative agent of bovine babesiosis, a potential risk to more than 500 million cattle worldwide. The vaccines currently available are based on attenuated parasites, which are difficult to produce, and are only recommended for use in bovines under one year of age. When used in older animals, these vaccines may cause life-threatening clinical symptoms and eventually death. The development of a multi-subunit recombinant vaccine against B. bovis would be attractive from an economic standpoint and, most importantly, could be recommended for animals of any age. In the present study, recombinant ectodomains of MSA-2a1, MSA-2b and MSA-2c antigens were expressed in Pichia pastoris yeast as secreted soluble peptides.
Results
The antigens were purified to homogeneity, and biochemically and immunologically characterized. A vaccine formulation was obtained by emulsifying a mixture of the three peptides with the adjuvant Montanide ISA 720, which elicited high IgG antibody titers against each of the above antigens. IgG antibodies generated against each MSA-antigen recognized merozoites and significantly inhibited the invasion of bovine erythrocytes. Cellular immune responses were also detected, which were characterized by splenic and lymph node CD4+ T cells producing IFN-γ and TNF-α upon stimulation with the antigens MSA-2a1 or MSA-2c.
Conclusions
These data strongly suggest the high protective potential of the presented formulation, and we propose that it could be tested in vaccination trials of bovines challenged with B. bovis
Fertility rates among very young adolescent women: temporal and spatial trends in Brazil
No full textAbstract\ud
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Background\ud
We assessed whether the reported decrease in fertility rates among 15 to 19 years old Brazilian adolescents has met with a parallel decrease in very young adolescent (10 to 14 years old) fertility rates. So we explored temporal trends for fertility rates among very young adolescents between 2000 and 2012 for Brazil as a whole, its regions and states; and also analyzed the spatial distribution of fertility rates among Brazilian municipalities in the years 2000 and 2012.\ud
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Methods\ud
We used data from the Information System on Live Births to calculate the rates. To examine the temporal trends, we used linear regression for time series with Prais-Winsten estimation, including the annual percentage change, for the country, regions, and states. To analyze the spatial distribution among Brazilian municipalities, we calculated the Global Moran Index and created a local Moran significance and cluster map through Local Indicators of Spatial Association (LISA). We also elaborated a thematic map with the rates using empirical Bayesian estimation.\ud
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Results\ud
Brazilian very young adolescent fertility rates remained high and stable throughout the 2000 to 2012 period, and significantly decreased in three out of 26 states, and in the federal district. On the other hand, an increase was observed in two Northern and Northeastern states. The rates were spatially dependent in Brazilian municipalities (Moran Index = 0.22 in 2012; p = 0.05). The maps indicated a heterogeneous distribution of the rates, with high-rate clusters predominant in the North and low-rate clusters predominant in the South, Southeast, and Midwest.\ud
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Conclusions\ud
Our findings indicate that Brazilian very young adolescent fertility rates have not decreased in parallel with adolescent fertility rates as they remain high and did not decrease from 2000 and 2012, even though a few states presented a decrease. Thus, these phenomena probably have distinct underlying causes that warrant further elucidation. Progress in this field is crucial for the development of specific policies and programs focused on very young adolescents
The Nanocrystalline SnO2–TiO2 System‒Part II: Surface Energies and Thermodynamic Stability
No full textThe thermodynamic stability of nanocrystalline SnO2–TiO2 solid solutions was studied experimentally. Microcalorimetry of water adsorption revealed a systematic decrease in the surface energy with increasing Ti4+ content in the SnO2-rich compositions, consistent with previous reports of Ti4+ segregation on the surface. The surface energy change was accompanied by an increase in the magnitude of the heat of water adsorption, also indicating a modification of the SnO2 surface by Ti4+. Supporting the water adsorption data, calculations using high-temperature oxide melt solution calorimetry data also suggest a decrease in the interface energies. A thermodynamic analysis showed that the observed surface energy decrease is responsible for an increase in the stability of solid solutions in the nanophase regime. Although a miscibility gap is expected in this system from bulk phase diagrams, the surface energy contribution modifies the bulk trend and promotes extensive solid solutions when the surface area is above a critical value dependent on the surface energy and the bulk enthalpy of mixing.CAPESCNP
Older Brazilian women’s experience of psychological domestic violence: a social phenomenological study
No full textAbstract
Background
Domestic violence is a global public health issue, as it is in Brazil. The psychological violence is one of the most prevalent forms of domestic violence, affecting more women than men. However, many older adults do not consider it as a type of domestic violence. In addiction, psychological violence has received little attention from researchers. So, this study aims to further understand the phenomenon of psychological domestic violence perpetrated by relatives against older adult women (60 years and older).
Methods
A qualitative study was conducted using a social phenomenological approach proposed by Alfred Schütz. In-depth interviews were conducted with 11 older Brazilian women from three different agencies, two in Campina Grande and one in São Bernardo do Campo. Data collection took place between November 2012 and February 2013. We performed data analysis using the key concepts (such as the world of everyday life, natural attitude, intersubjetivity, stock of knowledge, biographical situation, social action, motivation and typification) proposed by Alfred Schutz.
Results
Despite the fact that participants reported being psychologically abused, they also referred to being neglected and financially abused. They revealed being threatened, disrespected, neglected, financially abused, forced to do housework, and humiliated. Older women expressed feelings of sadness, anger, grief, and fear, which had negative effects on their health. Attempts by the participants to change their current situations were unsuccessful and resulted in feelings of helplessness. The abuser’s behaviour will change, and leaving the abusive situation were two possible outcomes pointed for participants.
Conclusions
A support network is crucial to help changing the behaviour of aggressors and/or to help older adult women leave the abusive situation. Further research is needed to understand the risk factors linked to abuse behaviours, to develop educational programs for the abusers, and to design social support for the victims
Effect of synaptic plasticity on functional connectivity and global activity of a neocortical network model
No full textWork funded by FAPESP-DFG (IRTG 1740/TRP 2011/50151-0) and FAPESP/CEPID/Neuromat (grant 2013/07699-0). ROS is supported by a CAPES MSc scholarship, RFOP is supported by a FAPESP PhD scholarship (grant 2013/25667-8), and ACR is supported by a CNPq research grant (PQ 306251/2014-0
Influence of obesity and cardiometabolic makers on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in adolescents: the healthy young cross-sectional study
No full textAbstract
Background
Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) is a good marker of cardiovascular risk in adults. It is strongly associated with stroke and many others cardiovascular events. Despite this, the impact of obesity on this enzyme activity and its relation to biomarkers of cardiovascular disease in adolescents is not very well investigated. The purpose of this article is to evaluate the influence of obesity and cardiometabolic markers on Lp-PLA2 activity in adolescents.
Results
This cross-sectional study included 242 adolescents (10–19 years) of both gender. These subjects were classified in Healthy Weight (n = 77), Overweight (n = 82) and Obese (n = 83) groups. Lipid profile, glucose, insulin, HDL size, LDL(−) and anti-LDL(−) antibodies were analyzed. The Lp-PLA2 activity was determined by a colorimetric commercial kit. Body mass index (BMI), waist circumference and body composition were monitored. Food intake was evaluated using three 24-hour diet recalls. The Lp-PLA2 activity changed in function to high BMI, waist circumference and fat mass percentage. It was also positively associated with HOMA-IR, glucose, insulin and almost all variables of lipid profile. Furthermore, it was negatively related to Apo AI (β = −0.137; P = 0.038) and strongly positively associated with Apo B (β = 0.293; P < 0.001) and with Apo B/Apo AI ratio (β = 0.343; P < 0.001). The better predictor model for enzyme activity, on multivariate analysis, included Apo B/Apo AI (β = 0.327; P < 0.001), HDL size (β = −0.326; P < 0.001), WC (β = 0.171; P = 0.006) and glucose (β = 0.119; P = 0.038). Logistic regression analysis demonstrated that changes in Apo B/Apo AI ratio were associated with a 73.5 times higher risk to elevated Lp-PLA2 activity.
Conclusions
Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with waist circumference, glucose, HDL size and Apo B/Apo AI ratio. These results suggest that Lp-PLA2 activity can be a cardiovascular biomarker in adolescence
Virulence genes of Rickettsia rickettsii are differentially modulated by either temperature upshift or blood-feeding in tick midgut and salivary glands
No full textAbstract\ud
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Background\ud
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Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever, is transmitted to humans by ticks. During tick feeding, R. rickettsii is exposed to both temperature elevation and components of the blood meal, which have previously been associated with the reactivation of its virulence. These environmental stimuli were also reported to modulate virulence genes of R. rickettsii infecting a set of organs of adult females of its natural vector, Amblyomma aureolatum.\ud
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Methods\ud
In this study, we determined the effects of a temperature upshift, blood-feeding, and both stimuli simultaneously on the expression of 85 selected genes of R. rickettsii infecting either the midgut (MG) or salivary glands (SG) of male and female A. aureolatum by microfluidic high-throughput RT-qPCR. These two organs are key for acquisition of this bacterium by the tick and transmission to the vertebrate host, respectively.\ud
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Results\ud
Data showed that these environmental stimuli exert distinct effects on rickettsial transcription depending on the colonized organ and gender of the vector. Temperature upshift induced the majority of differentially expressed genes of R. rickettsii in tick SG, including tRNA synthetases encoding genes. On the contrary, blood-feeding downregulated most of differentially expressed genes in both organs, but induced type IV secretion system components and OmpB in tick MG. The combined effects of both stimuli resulted in a merged gene expression profile representing features of each stimulus analyzed independently, but was more similar to the profile induced by blood-feeding.\ud
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Conclusion\ud
The upregulation of the majority of differentially expressed genes in tick SG by temperature upshift suggests that this stimulus is important to prepare R. rickettsii for transmission to the vertebrate host. Blood-feeding, on the other hand, induced important virulence genes in the tick MG, which might be associated with colonization of the tick and transmission to the vertebrate host. The role of the proteins identified in this study must be addressed and might help to define future targets to block tick infection, thereby preventing RMSF. To our knowledge, this is the first transcriptional tissue-specific study of a virulent strain of R. rickettsii infecting a natural tick vector.We would like to thank Dr. Milton Moraes and Tiana Rosa de Brito for\ud
microfluidic RT-qPCR technical assistance. We also thank Camila Dantas\ud
Malossi, Adriano Pinter, João F. Soares, and Francisco Borges Costa for technical\ud
assistance in tick colony maintenance. This work was supported by funds from\ud
the São Paulo Research Foundation (FAPESP; Grants 2008/53570-0 and 2013/\ud
26450-2), the National Council for Scientific and Technological Development\ud
[CNPq; the National Institutes of Science and Technology Program in Molecular\ud
Entomology (INCT-EM)], the Coordination for the Improvement of Higher\ud
Education Personnel (CAPES), and the Provost for Research of the University of\ud
São Paulo [Research Support Center on Bioactive Molecules from Arthropod\ud
Vectors (NAP-MOBIARVE)]. MFBMG and LAM were respectively supported\ud
by doctoral and master’s fellowships from FAPESP, and RDR received a\ud
post-doctoral fellowship provided by CAPES
Insulin-like growth factor-I serum levels and their biological effects on Leishmania isolates from different clinical forms of American tegumentary leishmaniasis
No full textAbstracts\ud
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Background\ud
American tegumentary leishmaniasis (ATL) in Brazil is mostly caused by Leishmania (Viannia) braziliensis, with known forms of the disease being cutaneous (CL), mucosal (ML) and disseminated (DL) leishmaniasis. The development of the lesion in ATL is related both to the persistence of the Leishmania in the skin and to the parasite-triggered immune and inflammatory responses that ensue lesions. In this context one factor with expected role in the pathogenesis is insulin-like growth factor (IGF)-I with known effects on parasite growth and healing and inflammatory processes. In the present study, we addressed the effect of IGF-I on intracellular amastigote isolates from CL, ML and DL patients within human macrophage and we evaluated the IGF-I and IGF-binding protein-3 (IGFBP3) serum levels in patients presenting different clinical forms and controls from the endemic area.\ud
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Methods\ud
We evaluated biological variability in the responses of intracellular amastigotes of Leishmania isolates derived from CL, ML, and DL patients from an area for ATL in response to IGF-I. Intracellular amastigote growth was evaluated using the human macrophage cell line THP-1. Arginase activity in infected cells was evaluated quantifying the generated urea concentration. Serum samples from patients and controls were assayed using chemiluminescent immunometric assay to determine IGF-I and IGFBP3 levels.\ud
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Results\ud
We observed an increase in intracellular parasitism upon IGF-I stimulus in 62.5 % of isolates from CL, in 85.7 % from ML and only 42.8 % from DL cases. In DL, the basal arginase activity was lower than that of CL. We then evaluated the IGF-I and IGFBP3 serum levels in patients, and we observed significantly lower levels in ML and DL than in CL and control samples.\ud
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Conclusions\ud
The data suggest that IGF-I is modulated distinctly in different clinical forms of tegumentary leishmaniasis. IGF-I seemingly exerts effect on parasite growth likely contributing to its persistence in the skin in earlier phase. In addition the decreased IGF-I serum levels may affect the modulation of inflammation and lesion healing in chronic phase. In view of potential role of IGF-I in the pathogenesis of ATL we can speculate on therapeutic procedures taking into account the local IGF-I level.This study was supported by Fundação de Amparo à Pesquisa do Estado de São\ud
Paulo (research fellowship 2008/2209-6 to LDS), Fundação de Amparo à Pesquisa\ud
do Estado da Bahia (research fellowship 1780–2007 to CMVV), Conselho Nacional\ud
de Pesquisa (fellowship to EMC, ARJ and HG, and grant 484499/2006) and the\ud
Soroepidemiology and Immunobiology Laboratory LIM/38 (HC-FMUSP)