Present situation and new strategies for Chagas disease chemotherapy: a proposal

Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914) and up to the drugs currently in use (nifurtimox and benznidazole), along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles), in separate form. Several diseases such as tuberculosis, leprosy and AIDS only came under control after they were treated with associations of drugs with different mechanisms of action. This not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .To this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i) nifurtimox (8 mg/kg/day) + benznidazole (5 mg/kg/day) x 60 consecutive days; (ii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + allopurinol (8-10 mg/kg/day) x 60 days and (iii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + ketoconazole, fluconazole or itraconazole (5-6 mg/kg/day) x 60 consecutive days. The doses of the drugs and the treatment schedules for the clinical trials must be adapted according to the side effects. From these, other double or triple associations could be made, using drugs with different mechanisms of action. This proposal does not exclude investigations on new drugs over the median and long terms, targeting other aspects of the metabolism of Trypanosoma cruzi. Until such time as the ideal drug for specific treatment of Chagas disease might be discovered, we need to develop new strategies for achieving greater efficacy with the old drugs in associations and to develop rational experimentation with new drugs.

Stocking densities and feeding strategies in shrimp and tilapia polyculture in tanks

The objective of this work was to evaluate the performance of Pacific marine shrimp (Litopenaeus vannamei) and tilapia (Oreochromis niloticus), in a polyculture in tanks subjected to different stocking densities and feeding strategies, in comparison with monoculture. Two experiments were performed, at the same time, in a completely randomized design with three treatments and four replicates each. Treatments for experiment I were: monoculture with 10 shrimp per m² (10S:0T); polyculture with 10 shrimp and 0.5 tilapia per m² (10S:0.5T); and polyculture with 10 shrimp and 1 tilapia per m² (10S:1T). Shrimp was the main crop, and feed was provided based on shrimp biomass. Treatments for experiment II were: monoculture with 2 tilapia per m² (2T:0S); polyculture with 2 tilapia and 2.5 shrimp per m² (2T:2.5S); and polyculture with 2 tilapia and 5 shrimp per m² (2T:5S). Tilapia was the main crop, and feed was provided based on fish requirements. In the experiment I, tilapia introduction to shrimp culture resulted in lower shrimp growth and poor feed conversion rate. In experiment II, shrimp introduction to tilapia culture did not interfere with fish performance. Polyculture is more efficient with the combination of 2 tilapia and 2.5 or 5 shrimp per m² and feed based on fish requirements.

Traditional and transgenic strategies for controlling tomato-infecting begomoviruses

Viruses of to the family Geminiviridae are considered some of the most important pathogens in tropical and subtropical regions of the world. Members of one Geminiviridae genus, Begomovirus, have been causing severe losses, particularly in tomato (Lycopersicon esculentum) production in the Americas and the Caribbean. Several new begomoviruses have been reported in the region and, at least one, Tomato yellow leaf curl virus (TYLCV), has been brought in from the Old World via infected transplants. In addition, the recombination events that are playing an important role in Begomovirus diversity have increased the complexity of their control. This scenario has led to the search for control measures that go beyond traditional host genetic resistance, chemical controls and cultural practices. In this review, besides the recommended classical control measures, transgenic approaches will be discussed, as well as the mechanisms involved in their successful control of viruses.

Solution of aerospace problems using structured and unstructured strategies

Products developed at industries, institutes and research centers are expected to have high level of quality and performance, having a minimum waste, which require efficient and robust tools to numerically simulate stringent project conditions with great reliability. In this context, Computational Fluid Dynamics (CFD) plays an important role and the present work shows two numerical algorithms that are used in the CFD community to solve the Euler and Navier-Stokes equations applied to typical aerospace and aeronautical problems. Particularly, unstructured discretization of the spatial domain has gained special attention by the international community due to its ease in discretizing complex spatial domains. This work has the main objective of illustrating some advantages and disadvantages of numerical algorithms using structured and unstructured spatial discretization of the flow governing equations. Numerical methods include a finite volume formulation and the Euler and Navier-Stokes equations are applied to solve a transonic nozzle problem, a low supersonic airfoil problem and a hypersonic inlet problem. In a structured context, these problems are solved using MacCormack’s implicit algorithm with Steger and Warming’s flux vector splitting technique, while, in an unstructured context, Jameson and Mavriplis’ explicit algorithm is used. Convergence acceleration is obtained using a spatially variable time stepping procedure.

Salivary cortisol as a tool for physiological studies and diagnostic strategies

Salivary cortisol is an index of plasma free cortisol and is obtained by a noninvasive procedure. We have been using salivary cortisol as a tool for physiological and diagnostic studies, among them the emergence of circadian rhythm in preterm and term infants. The salivary cortisol circadian rhythm in term and premature infants was established between 8 and 12 postnatal weeks. In the preterm infants the emergence of circadian rhythm was parallel to the onset of sleep rhythm. We also studied the use of salivary cortisol for screening for Cushing's syndrome (CS) in control and obese outpatients based on circadian rhythm and the overnight 1 mg dexamethasone (DEX) suppression test. Salivary cortisol was suppressed to less than 100 ng/dl after 1 mg DEX in control and obese patients. A single salivary cortisol measurement at 23:00 h and again after 1 mg DEX above the 90th percentile of the obese group values had sensitivity and specificity of 93 and 93% (23:00 h), and 91 and 94% (after DEX), respectively. The sensitivity improved to 100% when we combined both parameters. We also studied 11 CS children and 21 age-matched primary obese children for whom salivary cortisol sensitivity and specificity were 100/95% (23:00 h), and 100/95% (1 mg DEX), respectively. Similar to adults, sensitivity and specificity of 100% were obtained by combining 23:00 h and 1 mg DEX. The measurement of salivary cortisol is a useful tool for physiological studies and for the diagnosis of CS in children and adults on an outpatient basis.

Conventional and novel strategies in the treatment of adrenocortical cancer

Adrenocortical carcinoma is a highly malignant neoplasm with an incidence of two per million people per year. Several treatment strategies have resulted in temporary or partial tumor regression but very few cases have attained long survival. Surgical resection of the primary tumor and metastases is most effective. Several chemotherapeutic protocols have been employed with variable success. Mitotane (o,p'-DDD) is an adrenalytic drug effective in inducing a tumor response in 33% of patients treated. Mitotane requires metabolic transformation for therapeutic action. Tumors may vary in their ability to metabolize mitotane and the ability of tumors to transform mitotane may predict the clinical response to the drug. Preliminary data show a possible correlation between metabolic activity of neoplastic adrenocortical tissue and response to mitotane. We have attempted to develop mitotane analogs with enhanced adrenalytic effect. Compared to mitotane, a di-chloro compound, the bromo-chloro and di-bromo analogs appear to have a greater effect. Future approaches to the treatment of adrenocortical carcinoma are likely to be based on blocking or reversing the biological mechanisms of tumorigenesis. Angiogenic and chemotactic mechanisms may play a role in adrenal tumor growth and inhibition of these mechanisms may result in inhibition of tumor growth. New mitotane analogs with greater adrenalytic potential could be a promising approach to developing more effective and selective therapies for adrenal cancer. Alternative approaches should attempt to suppress tumor growth by means of compounds with anti-angiogenic and anti-chemotactic activity.

Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-β cells within the pancreas to β cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

The structuralist tradition in economics: methodological and macroeconomics aspects

This paper examines the structuralist tradition in economics, emphasizing the role that structures play in the economic growth of developing countries. Since the subject at hand is evidently too large to cover in a single article, an emphasis has been brought to bear upon the macroeconomic elements of such a tradition, while also exploring its methodological aspects. It begins by analysing some general aspects of structuralism in economics (its evolution and origins) associated with ECLAC thought, in this instance focusing on the dynamics of the center-periphery relationship. Thereafter, the macroeconomic structuralism derived from the works of Taylor (1983, 1991) is presented, followed by a presentation of neo-structuralism. Centred on the concept of systemic competitiveness, this approach defines a strategy to achieve the high road of globalization, understood here as an inevitable process in spite of its engagement being dependent on the policies adopted. The conclusions show the genuine contributions of this tradition to economic theory.

The art and learning patterns of knowing in nursing

Objective To identify the perception of the students about the use of art as a pedagogical strategy in learning the patterns of knowing in nursing; to identify the dimensions of each pattern valued in the analysis of pieces of art. Method Descriptive mixed study. Data collection used a questionnaire applied to 31 nursing students. Results In the analysis of the students’ discourse, it was explicit that empirical knowledge includes scientific knowledge, tradition and nature of care. The aesthetic knowledge implies expressiveness, subjectivity and sensitivity. Self-knowledge, experience, reflective attitude and relationships with others are the subcategories of personal knowledge and the moral and ethics support ethical knowledge. Conclusion It is possible to learn patterns of knowledge through art, especially the aesthetic, ethical and personal. It is necessary to investigate further pedagogical strategies that contribute to the learning patterns of nursing knowledge.

Variations in weed population densities, rate of change and community diversity in RR-soybeans and RR-maize strip crops under two herbicide strategies

Concerns about the sustainability of large-scale, direct-drilled RR-soybeans (Glycine max), and RR-maize (Zea mays) under monoculture in central Argentina are growing steadily. An experiment was conducted during three consecutive years to determine the effects of crops and systems (monocultures and strips) and herbicide strategy on weed density, population rate of change (l), b community diversity (H´), crop yields and Land Equivalent Ratio (LER). Not only crops but also crop systems differentially influenced weed densities along their growth and development. For crop harvests, weed densities increased in both maize crop systems as compared to in the one for soybeans, but the lowest increase occurred in soybean strips. Differences were leveled by both herbicide strategies, which achieved 73% efficacy during the critical periods in both crops. l of annual monocotyledonous increased, thus shifting the weed community composition. Species richness and H´ were not affected by crop systems, but both herbicide strategies, particularly POST, either in soybeans in monoculture or in maize strips, significantly enhanced H´. Crop yields significantly increased in the maize-strip system with POST (Year 1) or PRE (Years 2 and 3) strategies, thus increasing LER above 1. Herbicide Environmental Load treatments fall within very low or low field use rating.

Interests and Values in Obama's foreign Policy: Leading from Behind?

Abstract This study will exam the relative importance of values and interests in Obama's foreign policy, focusing on crucial cases: the military actions related to Afghanistan, Iraq, Libya, Non-Syria, Al-Qaeda and ISIL. We will argue that his "leading from behind" strategy is not very distant from the foreign and defense strategies of his post-Cold War predecessors, by which democracy is seen as an assurance to security. According to Obama's strategy, Americans will only provide support for the building of democracy in the target countries, while this task should be performed by the locals themselves. Americans will provide military training to the new governments as well so they can be responsible for their own security, including preventing regrouping of terrorists in their soil. If Obama opposes the imposing of democracy by the use of force, empirical data shows that his administration is "not prepared to accept" any option that threats US security or American liberal-democratic values, bringing in this way values and interests very close to each other.

Temporal trends and spatial distribution of unsafe abortion in Brazil, 1996-2012

OBJECTIVE To analyze temporal trends and distribution patterns of unsafe abortion in Brazil. METHODS Ecological study based on records of hospital admissions of women due to abortion in Brazil between 1996 and 2012, obtained from the Hospital Information System of the Ministry of Health. We estimated the number of unsafe abortions stratified by place of residence, using indirect estimate techniques. The following indicators were calculated: ratio of unsafe abortions/100 live births and rate of unsafe abortion/1,000 women of childbearing age. We analyzed temporal trends through polynomial regression and spatial distribution using municipalities as the unit of analysis. RESULTS In the study period, a total of 4,007,327 hospital admissions due to abortions were recorded in Brazil. We estimated a total of 16,905,911 unsafe abortions in the country, with an annual mean of 994,465 abortions (mean unsafe abortion rate: 17.0 abortions/1,000 women of childbearing age; ratio of unsafe abortions: 33.2/100 live births). Unsafe abortion presented a declining trend at national level (R2: 94.0%, p < 0.001), with unequal patterns between regions. There was a significant reduction of unsafe abortion in the Northeast (R2: 93.0%, p < 0.001), Southeast (R2: 92.0%, p < 0.001) and Central-West regions (R2: 64.0%, p < 0.001), whereas the North (R2: 39.0%, p = 0.030) presented an increase, and the South (R2: 22.0%, p = 0.340) remained stable. Spatial analysis identified the presence of clusters of municipalities with high values for unsafe abortion, located mainly in states of the North, Northeast and Southeast Regions. CONCLUSIONS Unsafe abortion remains a public health problem in Brazil, with marked regional differences, mainly concentrated in the socioeconomically disadvantaged regions of the country. Qualification of attention to women’s health, especially to reproductive aspects and attention to pre- and post-abortion processes, are necessary and urgent strategies to be implemented in the country.

Relationship of health workers with their organization and work: a cross-cultural study

ABSTRACT We analyzed the differences, by Student’s t-test and ANOVA, between nurses and physicians from Portugal, Poland, Spain, and United Kingdom regarding their relationship with their work and organization. In total, 1,401 professionals answered the HSA-QHPR questionnaire. There are different levels of connection between physicians and nurses. The United Kingdom has the lowest levels of connection with the work while Portugal has the highest levels of relationship with the organization. The results provide guidelines for the development of policies and differential strategies aimed at improving the quality of healthcare service.

Visceral leishmaniasis in Brazil: revisiting paradigms of epidemiology and control

In the last 20 years, despite the known underestimation of cases, Brazil registered a marked increase in the incidence of visceral leishmaniasis. The main goal of this review is to reflect on some aspects of this zoonosis in Brazil and also to encourage the discussion in order to find more viable, effective and affordable strategies to be implemented by the Brazilian Leishmaniasis Control Program. The current situation of visceral leishmaniasis in Brazil might be seen as a paradox: the most important aspects of the disease are known, but so far the control of this disease has not yet been achieved. The current control strategies have not been able to prevent the geographical expansion, and even a rise in the incidence and lethality of visceral leishmaniasis. There is a need not only for a better definition of priority areas, but also for the implementation of a fieldwork monitoring system to the disease surveillance that could permit a further evaluation of the control program in areas where visceral leishmaniasis is endemic.