Quality of life and the risk of contracting malaria by multivariate analysis in the Brazilian Amazon region

BACKGROUND: The incidence of malaria in the Amazon basin is closely related to social inequalities, given that precarious economic and socio-environmental conditions represent favourable factors for the transmission of the disease in tropical regions, such as the Brazilian state of Pará. In the present study, an association was found between the variation in a quality of life index (QLI), based on the socioeconomic differences between the municipalities of this state, and the risk of contracting malaria, based on the Annual Parasitic Index (API), with the primary objective of providing guidelines for the development of effective strategies for the control of the disease. METHODS: The API scores for the years between 2003 and 2011 were collected from the Brazilian Ministry of Health’s DATASUS database, and socioeconomic data for the 143 municipalities of Pará were obtained from the 2010 census. The data were analysed using multivariate factorial and correspondence techniques. RESULTS: The QLI was calculated for each municipality, of which, 69.23% were classified as having a poor or regular quality of life. The municipalities with poor QLI scores also presented moderate to high rates of malaria, with probabilities of 80.97% and 95.13%, respectively, while those with good QLI scores had low rates of malaria, with a probability of 79.24%. The results indicated a concentration of malaria in the south-west of the state of Pará, with an increase of 8.82% in the incidence of the disease over the study period, and the northeastern and Marajó mesoregions, where there was an increase of over 90%. In south-eastern Pará, by contrast, there was a marked reduction (78%) in the incidence of the disease, reflecting the heterogeneous distribution of malaria among the different municipalities and mesoregions of the state, especially those with moderate to high risk of transmission. CONCLUSIONS: These findings confirm that malaria is endemic to Pará and is typical of the state’s poorest areas, and that the distribution of the disease within the state indicates an intimate relationship with the living conditions of the population, affecting primarily the economically less privileged sectors of the society

The impact of long dry periods on the aboveground biomass in a tropical forest: 20 years of monitoring

Background Long-term studies of community and population dynamics indicate that abrupt disturbances often catalyse changes in vegetation and carbon stocks. These disturbances include the opening of clearings, rainfall seasonality, and drought, as well as fire and direct human disturbance. Such events may be super-imposed on longer-term trends in disturbance, such as those associated with climate change (heating, drying), as well as resources. Intact neotropical forests have recently experienced increased drought frequency and fire occurrence, on top of pervasive increases in atmospheric CO2 concentrations, but we lack long-term records of responses to such changes especially in the critical transitional areas at the interface of forest and savanna biomes. Here, we present results from 20 years monitoring a valley forest (moist tropical forest outlier) in central Brazil. The forest has experienced multiple drought events and includes plots which have and which have not experienced fire. We focus on how forest structure (stem density and aboveground biomass carbon) and dynamics (stem and biomass mortality and recruitment) have responded to these disturbance regimes. Results Overall, the biomass carbon stock increased due to the growth of the trees already present in the forest, without any increase in the overall number of tree stems. Over time, both recruitment and especially mortality of trees tended to increase, and periods of prolonged drought in particular resulted in increased mortality rates of larger trees. This increased mortality was in turn responsible for a decline in aboveground carbon toward the end of the monitoring period. Conclusion Prolonged droughts influence the mortality of large trees, leading to a decline in aboveground carbon stocks. Here, and in other neotropical forests, recent droughts are capable of shutting down and reversing biomass carbon sinks. These new results add to evidence that anthropogenic climate changes are already adversely impacting tropical forests

Keratocystic odontogenic tumor overexpresses invadopodia-related proteins, suggesting invadopodia formation

OBJECTIVE: Keratocystic odontogenic tumor (KOT) is an odontogenic neoplasm that shows aggressive clinical behavior and local invasiveness. Invadopodia are actin-rich cellular protrusions exhibiting proteolytic pericellular activity, thereby inducing focal invasion in neoplastic cells and increasing neoplasms aggressiveness. Thus, this study aimed to evaluate immunoexpression of invadopodia-related proteins, cortactin, MT1-MMP, Tks4, and Tks5, in KOT. STUDY DESIGN: Immunohistochemistry of 16 cases of KOT, eight cases of calcifying cystic odontogenic tumor (CCOT), and eight samples of the oral mucosa (OM) was carried out to assess the expression of the above described invadopodia-related proteins in the basal and suprabasal layer. RESULTS: KOT samples showed higher and significant immunoexpression of cortactin, MT1-MMP, TKs4, and TKs5 compared with the CCOT and OM samples. Significant expression of all these proteins was observed in the basal layer compared with the suprabasal layer in KOT. CONCLUSIONS: Overexpression of cortactin, MT1-MMP, TKs4, and TKs5 was observed in KOT compared with samples of CCOT and OM. These proteins were also overexpressed in the basal over the suprabasal layer of KOT samples. Taken together, these results suggest the participation of invadopodia-related proteins on the pathogenesis of this lesion

Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report

Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60). Treatment with several immunosuppressive regimens was tried, however the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing analysis of insulin receptor and post receptor signaling in skeletal muscle biopsy. The expression of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) was evaluated in total extract from muscle tissue by Western blotting. Basal IR, IRS-1 and GLUT-4 expression was detected, however receptor autophosphorylation was not observed. A study of translocation of GLUT-4 to plasma membrane showed that tissue presented low levels of membrane-associated GLUT-4. When in vitro stimulation was undertaken, tissue was capable to be responsive to insulin. Our results suggest that even though IR expression was normally occurring, IR β-subunit tyrosine kinase activity in muscle was down-regulated leading to alterations in insulin post receptor signaling. Consistent with normal insulin receptor and post receptor signaling, our results were compatible with decreased insulin binding to IR probably due to neutralization by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators