Validity of the Brazilian version of WHOQOL-BREF in depressed patients using Rasch modelling

OBJECTIVE: To assess the validity of the Brazilian version of the World Health Organization Quality of Life Instrument - Abbreviated version (WHOQOL-BREF) in adults with major depression, using Rasch modelling. METHODS: Study analyzing data from the baseline sample of the Longitudinal Investigation of Depression Outcomes in Brazil, including a total of 208 patients with major depression recruited in a primary care service in Porto Alegre (Southern Brazil), in 1999. The Center for Epidemiological Studies Depression Scale was used to assess intensity of depression; the WHOQOL-BREF to assess generic quality of life; and the Composite International Diagnostic Interview version 2.1 for the diagnosis of depression. RESULTS: In the Rasch analysis, the four domains of WHOQOL-BREF showed appropriate fit to this model. Some items needed adjustments: four items were rescored (pain, finances, services, and transport); two items (work and activity) were identified as having dependency of responses, and one item was deleted (sleep) due to multidimensionality. CONCLUSIONS: The validation of the WHOQOL-BREF Brazilian version using Rasch analysis complements previous validation studies, evidencing the robustness of this instrument as a generic cross-cultural quality of life measure.

Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

Pentamidine (PEN) is an alternative compound to treat antimony-resistant leishmaniasis patients, which cellular target remains unclear. One approach to the identification of prospective targets is to identify genes able to mediate PEN resistance following overexpression. Starting from a genomic library of transfected parasites bearing a multicopy episomal cosmid vector containing wild-type Leishmania major DNA, we isolated one locus capable to render PEN resistance to wild type cells after DNA transfection. In order to map this Leishmania locus, cosmid insert was deleted by two successive sets of partial digestion with restriction enzymes, followed by transfection into wild type cells, overexpression, induction and functional tests in the presence of PEN. To determine the Leishmania gene related to PEN resistance, nucleotide sequencing experiments were done through insertion of the transposon Mariner element of Drosophila melanogaster (mosK) into the deleted insert to work as primer island. Using general molecular techniques, we described here this method that permits a quickly identification of a functional gene facilitating nucleotide sequence experiments from large DNA fragments. Followed experiments revealed the presence of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has now been analyzed.

Modelling Amazonian forest eddy covariance data: a comparison of big leaf versus sun/shade models for the C-14 tower at Manaus I. Canopy photosynthesis

In this study, we concentrate on modelling gross primary productivity using two simple approaches to simulate canopy photosynthesis: "big leaf" and "sun/shade" models. Two approaches for calibration are used: scaling up of canopy photosynthetic parameters from the leaf to the canopy level and fitting canopy biochemistry to eddy covariance fluxes. Validation of the models is achieved by using eddy covariance data from the LBA site C14. Comparing the performance of both models we conclude that numerically (in terms of goodness of fit) and qualitatively, (in terms of residual response to different environmental variables) sun/shade does a better job. Compared to the sun/shade model, the big leaf model shows a lower goodness of fit and fails to respond to variations in the diffuse fraction, also having skewed responses to temperature and VPD. The separate treatment of sun and shade leaves in combination with the separation of the incoming light into direct beam and diffuse make sun/shade a strong modelling tool that catches more of the observed variability in canopy fluxes as measured by eddy covariance. In conclusion, the sun/shade approach is a relatively simple and effective tool for modelling photosynthetic carbon uptake that could be easily included in many terrestrial carbon models.

Dynamics of experimental populations of native and introduced blowflies (Diptera: Calliphoridae): mathematical modelling and the transition from asymptotic equilibrium to bounded oscillations

The equilibrium dynamics of native and introduced blowflies is modelled using a density-dependent model of population growth that takes into account important features of the life-history in these flies. A theoretical analysis indicates that the product of maximum fecundity and survival is the primary determinant of the dynamics. Cochliomyia macellaria, a blowfly native to the Americas and the introduced Chrysomya megacephala and Chrysomya putoria, differ in their dynamics in that the first species shows a damping oscillatory behavior leading to a one-point equilibrium, whereas in the last two species population numbers show a two-point limit cycle. Simulations showed that variation in fecundity has a marked effect on the dynamics and indicates the possibility of transitions from one-point equilibrium to bounded oscillations and aperiodic behavior. Variation in survival has much less influence on the dynamics.

The carbohydrate-binding specificity and molecular modelling of Canavalia maritima and Dioclea grandiflora lectins

The carbohydrate-binding specificity of lectins from the seeds of Canavalia maritima and Dioclea grandiflora was studied by hapten-inhibition of haemagglutination using various sugars and sugar derivatives as inhibitors, including N-acetylneuraminic acid and N-acetylmuramic acid. Despite some discrepancies, both lectins exhibited a very similar carbohydrate-binding specificity as previously reported for other lectins from Diocleinae (tribe Phaseoleae, sub-tribe Diocleinae). Accordingly, both lectins exhibited almost identical hydropathic profiles and their three-dimensional models built up from the atomic coordinates of ConA looked very similar. However, docking experiments of glucose and mannose in their monosaccharide-binding sites, by comparison with the ConA-mannose complex used as a model, revealed conformational changes in side chains of the amino acid residues involved in the binding of monosaccharides. These results fully agree with crystallographic data showing that binding of specific ligands to ConA requires conformational chances of its monosaccharide-binding site.

Different approaches to modelling the cost-effectiveness of schistosomiasis control

This paper reviews three different approaches to modelling the cost-effectiveness of schistosomiasis control. Although these approaches vary in their assessment of costs, the major focus of the paper is on the evaluation of effectiveness. The first model presented is a static economic model which assesses effectiveness in terms of the proportion of cases cured. This model is important in highlighting that the optimal choice of chemotherapy regime depends critically on the level of budget constraint, the unit costs of screening and treatment, the rates of compliance with screening and chemotherapy and the prevalence of infection. The limitations of this approach is that it models the cost-effectiveness of only one cycle of treatment, and effectiveness reflects only the immediate impact of treatment. The second model presented is a prevalence-based dynamic model which links prevalence rates from one year to the next, and assesses effectiveness as the proportion of cases prevented. This model was important as it introduced the concept of measuring the long-term impact of control by using a transmission model which can assess reduction in infection through time, but is limited to assessing the impact only on the prevalence of infection. The third approach presented is a theoretical framework which describes the dynamic relationships between infection and morbidity, and which assesses effectiveness in terms of case-years prevented of infection and morbidity. The use of this model in assessing the cost-effectiveness of age-targeted treatment in controlling Schistosoma mansoni is explored in detail, with respect to varying frequencies of treatment and the interaction between drug price and drug efficacy.

A theoretical model of the tridimensional structure of Bacillus thuringiensis subsp. medellin Cry 11Bb toxin deduced by homology modelling

Cry11Bb is an insecticidal crystal protein produced by Bacillus thuringiensis subsp. medellin during its stationary phase; this ¶-endotoxin is active against dipteran insects and has great potential for mosquito borne disease control. Here, we report the first theoretical model of the tridimensional structure of a Cry11 toxin. The tridimensional structure of the Cry11Bb toxin was obtained by homology modelling on the structures of the Cry1Aa and Cry3Aa toxins. In this work we give a brief description of our model and hypothesize the residues of the Cry11Bb toxin that could be important in receptor recognition and pore formation. This model will serve as a starting point for the design of mutagenesis experiments aimed to the improvement of toxicity, and to provide a new tool for the elucidation of the mechanism of action of these mosquitocidal proteins.

Mycobacterium avium restriction fragment lenght polymorphism-IS IS1245 and the simple double repetitive element polymerase chain reaction typing method to screen genetic diversity in Brazilian strains

Simple double repetitive element polymerase chain reaction (MaDRE-PCR) and Pvu II-IS1245 restriction fragment length polymorphism (RFLP) typing methods were used to type 41 Mycobacterium avium isolates obtained from 14 Aids inpatients and 10 environment and animals specimens identified among 53 mycobacteria isolated from 237 food, chicken, and pig. All environmental and animals strains showed orphan patterns by both methods. By MaDRE-PCR four patients, with multiple isolates, showed different patterns, suggesting polyclonal infection that was confirmed by RFLP in two of them. This first evaluation of MaDRE-PCR on Brazilian M. avium strains demonstrated that the method seems to be useful as simple and less expensive typing method for screening genetic diversity in M. avium strains on selected epidemiological studies, although with limitation on analysis identical patterns except for one band.

Germline transformation of Aedes fluviatilis (Diptera:Culicidae) with the piggyBac transposable element

The technique to generate transgenic mosquitoes requires adaptation for each target species because of aspects related to species biology, sensitivity to manipulation and rearing conditions. Here we tested different parameters on the microinjection procedure in order to obtain a transgenic Neotropical mosquito species. By using a transposon-based strategy we were able to successfully transform Aedes fluviatilis (Lutz), which can be used as an avian malaria model. These results demonstrate the usefulness of the piggyBac transposable element as a transformation vector for Neotropical mosquito species and opens up new research frontiers for South American mosquito vectors.

Spatial modelling of Lutzomyia (Nyssomyia) whitmani s.l. (Antunes & Coutinho, 1939) (Diptera: Psychodidae: Phlebotominae) habitat suitability in the state of Mato Grosso, Brazil

Lutzomyia (Nyssomyia) whitmani s.l.is the main vector of cutaneous leishmaniasis in state of Mato Grosso, but little is known about environmental determinants of its spatial distribution on a regional scale. Entomologic surveys of this sand fly species, conducted between 1996 and 2001 in 41 state municipalities, were used to investigate the relationships between environmental factors and the presence of the species, and to develop a spatial model of habitat suitability. The relationship between averaged CDC light trap indexes and 15 environmental and socio-economic factors were tested by logistic regression (LR) analysis. Spatial layers of deforestation tax and the Brazilian index of gross net production (IGNP) were identified as significant explanatory variables for vector presence in the LR model, and these were then overlaid with habitat maps. The highest habitat suitability in 2001 was obtained for the heavily deforested areas in the Central-North, South, East, and Southwest of Mato Grosso, particularly in municipalities with lower IGNP values.

Ecological niche modelling and differentiation between Rhodnius neglectus Lent, 1954 and Rhodnius nasutus Stål, 1859 (Hemiptera: Reduviidae: Triatominae) in Brazil

Ecological niche modelling was used to predict the potential geographical distribution of Rhodnius nasutus Stål and Rhodnius neglectus Lent, in Brazil and to investigate the niche divergence between these morphologically similar triatomine species. The distribution of R. neglectus covered mainly the cerrado of Central Brazil, but the prediction maps also revealed its occurrence in transitional areas within the caatinga, Pantanal and Amazon biomes. The potential distribution of R. nasutus covered the Northeastern Region of Brazil in the semi-arid caatinga and the Maranhão babaçu forests. Clear ecological niche differences between these species were observed. R. nasutus occurred more in warmer and drier areas than R. neglectus. In the principal component analysis PC1 was correlated with altitude and temperature (mainly temperature in the coldest and driest months) and PC2 with vegetation index and precipitation. The prediction maps support potential areas of co-occurrence for these species in the Maranhão babaçu forests and in caatinga/cerrado transitional areas, mainly in state of Piaui. Entomologists engaged in Chagas disease vector surveillance should be aware that R. neglectus and R. nasutus can occur in the same localities of Northeastern Brazil. Thus, the identification of bugs in these areas should be improved by applying morphometrical and/or molecular methods.

Coxiella burnetii, the agent of Q fever in Brazil: its hidden role in seronegative arthritis and the importance of molecular diagnosis based on the repetitive element IS1111 associated with the transposase gene

Coxiella burnetii is the agent of Q fever , an emergent worldwide zoonosis of wide clinical spectrum. Although C. burnetii infection is typically associated with acute infection, atypical pneumonia and flu-like symptoms, endocarditis, osteoarticular manifestations and severe disease are possible, especially when the patient has a suppressed immune system; however, these severe complications are typically neglected. This study reports the sequencing of the repetitive element IS1111 of the transposase gene of C. burnetii from blood and bronchoalveolar lavage (BAL) samples from a patient with severe pneumonia following methotrexate therapy, resulting in the molecular diagnosis of Q fever in a patient who had been diagnosed with active seronegative polyarthritis two years earlier. To the best of our knowledge, this represents the first documented case of the isolation of C. burnetii DNA from a BAL sample.

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

Modelling the risk of nitrate leaching from two soils amended with five different biosolids

High N concentrations in biosolids are one of the strongest reasons for their agricultural use. However, it is essential to understand the fate of N in soils treated with biosolids for both plant nutrition and managing the environmental risk of NO3--N leaching. This work aimed at evaluating the risk of NO3--N leaching from a Spodosol and an Oxisol, each one treated with 0.5-8.0 dry Mg ha-1 of fresh tertiary sewage sludge, composted biosolids, limed biosolids, heat-dried biosolids and solar-irradiated biosolids. Results indicated that under similar application rates NO3--N accumulated up to three times more in the 20 cm topsoil of the Oxisol than the Spodosol. However, a higher water content held at field capacity in the Oxisol compensated for the greater nitrate concentrations. A 20 % NO3--N loss from the root zone in the amended Oxisol could be expected. Depending on the biosolids type, 42 to 76 % of the NO3--N accumulated in the Spodosol could be expected to leach down from the amended 20 cm topsoil. NO3--N expected to leach from the Spodosol ranged from 0.8 (composted sludge) to 3.5 times (limed sludge) the amounts leaching from the Oxisol treated alike. Nevertheless, the risk of NO3--N groundwater contamination as a result of a single biosolids land application at 0.5-8.0 dry Mg ha-1 could be considered low.

Modelling of soil penetration resistance for an oxisol under no-tillage

Soil penetration resistance is an important property that affects root growth and elongation and water movement in the soil. Since no-till systems tend to increase organic matter in the soil, the purpose of this study was to evaluate the efficiency with which soil penetration resistance is estimated using a proposed model based on moisture content, density and organic matter content in an Oxisol containing 665, 221 and 114 g kg-1 of clay, silt and sand respectively under annual no-till cropping, located in Londrina, Paraná State, Brazil. Penetration resistance was evaluated at random locations continually from May 2008 to February 2011, using an impact penetrometer to obtain a total of 960 replications. For the measurements, soil was sampled at depths of 0 to 20 cm to determine gravimetric moisture (G), bulk density (D) and organic matter content (M). The penetration resistance curve (PR) was adjusted using two non-linear models (PR = a Db Gc and PR' = a Db Gc Md), where a, b, c and d are coefficients of the adjusted model. It was found that the model that included M was the most efficient for estimating PR, explaining 91 % of PR variability, compared to 82 % of the other model.