The long-term administration of calcineurin inhibitors decreases antioxidant enzyme activity in the rat parotid and submandibular salivary glands

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Transposition burst of mariner-like elements in the sequenced genome of Rhodnius prolixus

Transposable elements (TEs) are widespread in insect´s genomes. However, there are wide differences in the proportion of the total DNA content occupied by these repetitive sequences in different species. We have analyzed the TEs present in R. prolixus (vector of the Chagas disease) and showed that 3.0% of this genome is occupied by Class II TEs, belonging mainly to the Tc1-mariner superfamily (1.65%) and MITEs (1.84%). Interestingly, most of this genomic content is due to the expansion of two subfamilies belonging to: irritans himar, a well characterized subfamily of mariners, and prolixus1, one of the two novel subfamilies here described. The high amount of sequences in these subfamilies suggests that bursts of transposition occurred during the life cycle of this family. In an attempt to characterize these elements, we performed an in silico analysis of the sequences corresponding to the DDD/E domain of the transposase gene. We performed an evolutionary analysis including network and Bayesian coalescent-based methods in order to infer the dynamics of the amplification, as well as to estimate the time of the bursts identified in these subfamilies. Given our data, we hypothesized that the TE expansions occurred around the time of speciation of R. prolixus around 1.4 mya. This suggestion lays on the Transposon Model of TE evolution, in which the members of a TE population that are replicative active are present at multiple loci in the genome, but their replicative potential varies, and of the Life Cycle Model that states that when present-day TEs have been involved in amplification bursts, they share an ancestral copy that dates back to this initial amplification.

Auditory steady-state response in the first six months of life

Objective: To characterize the thresholds of the auditory steady-state response that relates to term newborns and infants. Design: The study was cross-sectional using auditory steadystate response assessment, and the real-ear-to-dial difference was measured in the external auditory canal. Study Sample: The study group included 60 newborns and infants between the age of 0 and 6 months. Results: A statistically significant difference was found in the carrier frequency variable for auditory steady-state response thresholds but not in comparison to ages. Furthermore, there is an association between auditory steady-state response thresholds and the real-ear-to-dial difference. Conclusion: The same threshold can be used as a normality reference for this age range, with distinct values for the different carrier frequencies. The influence of external auditory canal amplification should be taken into account.

Selection for Increased Starvation Resistance Using Drosophila melanogaster: Investigating Physiological and Life History Trait Responses to Starvation and Dietary Supplementation in the Context of an Obese Phenotype

Artificial selection for starvation resistance provided insight into the relationships between evolved physiological and life history trait responses following exposure to biologically induced stress. Investigations of alterations to body composition, metabolic rate, movement, and life history traits including development time, female egg production, and longevity in response to brief periods of starvation were conducted on genetically based starvation-resistant and control lines of Drosophila melanogaster. Analysis of the starvation-resistant lines indicated increased energy storage with increased triglyceride deposition and conversion of carbohydrates to lipid, as identified by respiratory quotient values. Correlations between reductions in metabolic rates and movement in the starvation-resistant lines, suggested the presence of an evolved physiological response resulting in energy conservation. Investigations of life history traits in the starvation-resistant lines indicated no significant differences in development time or reproduction between the selected and control lines. Measurements of longevity, however, indicated a significant reduction in starvation-resistant D. melanogaster lifespan. These results suggested that elevated lipid concentrations, similar to that observed with obesity, were correlated with premature mortality. Exposure of the starvation-resistant and control lines to diets supplemented with glucose, palmitic acid, and a 2:1 mixture of casein to albumin were used to investigate alterations in body composition, movement, and life history traits. Results obtained from this study indicated that increased sugar in the diet led to increased carbohydrate, glycogen, total sugar, trehalose, and triglyceride concentrations, while increased fat and protein in the diet resulted in increased soluble protein, carbohydrate, glycogen, total sugar, and trehalose concentrations. Examination of life history trait responses indicated reduced fecundity in females exposed to increased glucose concentrations. Increased supplementations of palmitic acid was consistently correlated with an overall reduction in lifespan in both the starvation-resistant and control Drosophila lines, while measurements of movement indicated increased female activity levels in flies exposed to diets supplemented with fat and protein. Analyses of the physiological and life history trait responses to starvation and dietary supplementation on Drosophila melanogaster used in the present study has implications for investigating the mechanisms underlying the development and persistence of human obesity and associated metabolic disorders.

Lipid levels in the second year of life among HIV-infected and HIV-exposed uninfected Latin American children

Background: Dyslipidemia is observed among older children and adults with HIV. We examined nonfasting cholesterol and triglycerides in two groups of 12-23-month-old Latin American children - HIV-infected vs. HIV-exposed but uninfected (HEU). Methods: HIV-infected and HEU children in Latin America and Jamaica were enrolled in an observational cohort. Eligibility for this analysis required having cholesterol and triglyceride results available during the second year of life. Results: HIV-infected (n = 83) children were slightly older at the time of lipid testing than the HEU (n 681). Forty percent of the HIV-infected children were on protease inhibitor-based antiretroviral therapy (ART); 41% were not on ART. There was no statistically significant difference in mean cholesterol concentrations (mg/dl) by HIV status; however, the HIV-infected children had higher mean triglyceride concentrations. The prevalence of high cholesterol (>200 mg/dl) and high triglycerides (>110 mg/dl) was higher among the HIV-infected vs. HEU. Among the HIV-infected children, mean cholesterol and triglyceride concentrations varied by ART. Children receiving no ART had a significantly lower mean cholesterol concentration. Those receiving protease inhibitor-containing ART had a significantly higher mean triglyceride concentration compared to the other two antiretroviral regimen groups. Conclusion: A greater proportion of HIV-infected children at 12-23 months have hyperlipidemia when compared to HEU children, with the highest triglyceride concentrations observed among those receiving protease inhibitor-containing ART, and the lowest cholesterol levels among those not receiving ART. Implications of these findings will require continued follow-up of HIV-infected children who initiate therapy early in life. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Evaluation of quality of life in severely obese patients after bariatric surgery carried out in the public healthcare system

Objectives: To assess QoL of obese patients in the Brazilian public healthcare system, before and after bariatric surgery, and to determine the appropriateness of the Moorehead-Ardelt Questionnaire II (M-A-QoLQII) compared with the Short-Form Health Survey (SF-36). Subjects and methods: Forty-one severe obese patients in a waiting-list, and 84 patients who underwent bariatric surgery were included. Correlations were tested and reliability determined by the Cronbach's coefficient. Results: BMI differed between the pre- and post-surgery groups (52.3 +/- 8.3 kg/m(2) vs. 32.5 +/- 6.4 kg/m(2), p < 0.001). The latter showed better scores in the SF-36 domains than in the pre-surgery. SF-36 and M-A-QoLQII categories were correlated (r = 0.53, 0.49 and 0.47, for vitality, mental health, and general health domains, p < 0.001). In the logistic regression, age, previous BMI, and loss of excess weight were associated with functional capacity. Conclusions:The outcomes of bariatric surgery obtained in a Brazilian public healthcare center were successful. M-A-QoLII represents a useful tool to assess surgery outcomes, including QoL. Arq Bras Endocrinol Metab. 2012;56(1):33-8

Evaluating the legacy of landscape history: extinction debt and species credit in bird and small mammal assemblages in the Brazilian Atlantic Forest

There is now an extensive literature on extinction debt following deforestation. However, the potential for species credit in landscapes that have experienced a change from decreasing to expanding forest cover has received little attention. Both delayed responses should depend on current landscape forest cover and on species life-history traits, such as longevity, as short-lived species are likely to respond faster than long-lived species. We evaluated the effects of historical and present-day local forest cover on two vertebrate groups with different longevities understorey birds and non-flying small mammals - in forest patches at three Atlantic Forest landscapes. Our work investigated how the probability of extinction debt and species credit varies (i) amongst landscapes with different proportions of forest cover and distinct trajectories of forest cover change, and (ii) between taxa with different life spans. Our results suggest that the existence of extinction debt and species credit, as well as the potential for their future payment and/or receipt, is not only related to forest cover trajectory but also to the amount of remaining forest cover at the landscape scale. Moreover, differences in bird and small mammal life spans seem to be insufficient to affect differently their probability of showing time-delayed responses to landscape change. Synthesis and applications. Our work highlights the need for considering not only the trajectory of deforestation/regeneration but also the amount of forest cover at landscape scale when investigating time-delayed responses to landscape change. As many landscapes are experiencing a change from decreasing to expanding forest cover, understanding the association of extinction and immigration processes, as well as their interactions with the landscape dynamic, is a key factor to plan conservation and restoration actions in human-altered landscapes.

Sponges as substrata and early life history of the tubulariid Zyzzyzus warreni (Cnidaria: Hydrozoa) in the Sao Sebastiao Channel, Brazil

The hydroid Zyzzyzus warreni is usually found in shallow coastal waters forming aggregations of solitary polyps embedded in demosponges. Early life history transformations and settlement responses by the actinulae of this hydroid were studied in the laboratory using 13 species of sponges and 2 species of algae collected in the Sao Sebastiao Channel (Brazil) as substrata. The absence of oral tentacles and mouth in the actinulae and early events of metamorphosis suggest that these larvae are unable to spend long periods in the plankton and attach quickly near conspecifics when a preferred substratum is encountered. The time required for settlement and the number of elicited settlings indicated four settlement responses: (a) frequent and short-time settlement, in actinulae exposed to Halichondria cebimarensis, Mycale angulosa, M. aff. americana, M. laxissima (skeleton) and Tedania ignis; (b) moderate and delayed settlement, in actinulae exposed to Aplysina caissara, A. fulva, Haliclona melana and M. microsigmatosa; (c) no settlement, in actinulae exposed to Suberites aurantiacus and to the algae Hypnea musciformis and Sargassum cymosum; and (d) lethal response, in actinulae exposed to Amphimedon viridis, Aplysilla rosea, Dragmacidon reticulatum and M. laxissima. These responses indicate a considerable degree of species discrimination by the actinulae and are consistent with substrata used by the hydroid in the natural environment.

Evolution of Precambrian life in the Brazilian geological record

Precambrian rocks comprise nearly one-quarter of the surface of Brazil and range from Paleoarchean (ca. 3.6 Ga) to the latest Ediacaran (0.542 Ga) in age. Except for controversial phosphatized 'embryo-like' microfossils like those from the lower Ediacaran Doushantuo Formation, China and complex rangeomorphs, Brazilian research has revealed all major categories of Precambrian life forms described elsewhere - microbialites, biomarkers, silicified microfossils, palynomorphs, vase-shaped microfossils, macroalgae, metazoans, vendobionts and ichnofossils - but the paleobiological significance of this record has been little explored. At least four occurrences of these fossils offer promise for increased understanding of the following aspects of Precambrian biospheric evolution: (i) the relationship of microbialites in 2.1-2.4 Ga old carbonates of the Minas Supergroup in the Quadrilatero Ferrifero, Minas Gerais (the oldest Brazilian fossils) to the development of the early oxygenic atmosphere and penecontemporaneous global tectonic and climatic events; (ii) the evolutionary and biostratigraphic significance of Mesoproterozoic to Ediacaran organic-walled microfossils in central-western Brazil; (iii) diversity and paleoecological significance of vase-shaped heterotrophic protistan microfossils in the Urucum Formation (Jacadigo Group) and possibly the Bocaina Formation (Corumba Group), of Mato Grosso do Sul; and (iv) insights into the record of skeletogenesis and paleoecology of latest Ediacaran metazoans as represented by the abundant organic carapaces of Corumbella and calcareous shells of the index fossil Cloudina, of the Corumba Group, Mato Grosso do Sul. Analysis of the Brazilian Precambrian fossil record thus holds great potential for augmenting paleobiological knowledge of this crucial period on Earth and for developing more robust hypotheses regarding possible origins and evolutionary pathways of biospheres on other planets. Received 26 February 2012, accepted 17 May 2012, first published online 18 June 2012

Chronic Pain and Depression in the Quality of Life of Women With Migraine - A Controlled Study

Background. Migraine is comorbid to depression and widespread chronic pain (WCP), but the influence of these conditions on the health-related quality of life (HRQoL) of individuals with episodic (EM) and chronic migraine (CM) is poorly understood. Objective.-To assess the prevalence of depressive symptoms and WCP in individuals with EM and CM, as well as to estimate the joint impact of these conditions on the HRQoL of these individuals. Methods.-All women aged 18 to 65 years with a first diagnosis of EM or CM from September of 2006 to September of 2008 seen in an outpatient headache service were invited to participate. They were asked to attend a separate appointment in the service, and to bring another woman of similar age that also agreed to participate. Depressive symptoms were assessed using the Beck Depression Inventory. Questions about WCP followed the protocol of the American College of Rheumatology. HRQoL was assessed using the Short-Form 36 (SF-36). Multivariate analysis modeled HRQoL as a function of headache status, depressive symptoms, and pain, using quantile regression. Results.-Sample consisted of 179 women, 53 in the EM group, 37 in the CM group and 89 in control group. Groups did not differ by demographics. Mean scores of SF-36 were 53.6 (standard deviation [SD] = 23.5) for EM, 44.2 (SD = 18.5) for CM and 61.8 (SD = 21.5) for controls. In multivariate analysis, SF-36 scores were predicted by a CM status (P =.02; -10.05 [95% CI -18.52; -1.58]) and by a Beck Depression Inventory score (P <.01; -1.27 [95% CI -1.55; -0.99]). The influence of WCP in the SF-36 scores approached significance (P =.08; -0.78 [95% CI -1.64; 0.88]). Age did not contribute to the model. Conclusion.-Women with migraine are at an increased chance of WCP, and the chance increases as a function of headache frequency. Both depressive symptoms and CM independently predict HRQoL status.

Physical Activity In Daily Life In Brazilian COPD Patients During and After Exacerbation

Background: Although hospitalization is recognized as an important cause of reduction in physical activity in daily life (PADL) in COPD, there is only one study evaluating this effect, and it was performed in European COPD patients who have a lower PADL than that of South American COPD patients. Objectives: To investigate the effect of hospitalization due to acute exacerbation of PADL in Brazilian COPD patients and to evaluate the factors that determines the physical activity levels during hospitalization and after discharge. Methods: PADL was quantified using a 3-axis accelerometer on the 3rd day of hospitalization and 1 month after discharge in Brazilian COPD patients who were hospitalized due to disease exacerbation. Six-minute walking distance (6MWD), lower limb strength and pulmonary function were also evaluated. Results: A total of 20 patients completed the study. During hospitalization, patients spent most of the time (87%) lying down or sitting; however, 1 month after they were walking >40 min/day. In addition, patients with prior hospitalization had a lower level of physical activity compared to those without a previous history of hospitalization. The time spent walking during hospitalization was significantly explained by the quadriceps strength (r(2) = 0.29; p < 0.05), while 1 month after, the time spent walking was only significantly explained by the 6MWD (r(2) = 0.51; p = 0.02). Conclusions: Brazilian COPD patients are inactive during hospitalization but become active 1 month after discharge. Previously hospitalized are more inactive both during and after exacerbation. The quadriceps strength and 6MWD explain the physical activity levels during hospitalization and at home, respectively.

The neonatal immune system: immunomodulation of infections in early life

The innate and adaptive immune responses in neonates are usually functionally impaired when compared with their adult counterparts. The qualitative and quantitative differences in the neonatal immune response put them at risk for the development of bacterial and viral infections, resulting in increased mortality. Newborns often exhibit decreased production of Th1-polarizing cytokines and are biased toward Th2-type responses. Studies aimed at understanding the plasticity of the immune response in the neonatal and early infant periods or that seek to improve neonatal innate immune function with adjuvants or special formulations are crucial for preventing the infectious disease burden in this susceptible group. Considerable studies focused on identifying potential immunomodulatory therapies have been performed in murine models. This article highlights the strategies used in the emerging field of immunomodulation in bacterial and viral pathogens, focusing on preclinical studies carried out in animal models with particular emphasis on neonatal-specific immune deficits.

Questionnaire for monitoring auditory and language development in the first year of life

Purpose: To validate a monitoring questionnaire about hearing and language development applied by community health agents in the first year of life. Methods: Seventy six community health agents, previously trained on infant hearing health, administered a questionnaire to the families of 304 children with ages from 0 to 1 year. The questionnaire contains questions regarding hearing and language development and, for all age groups, the question “Does your child hear well?” was presented. The validity of the questionnaire was assessed by analyzing false positive and false negative rates of the identified children. A double-blind study was conducted so that all children assessed by the questionnaire were submitted to hearing evaluation performed by audiologists. Results: Four children (1.32%) were diagnosed with sensorineural hearing loss (two unilateral), and 69 (22.7%) with conductive hearing loss. The monitoring questionnaire showed specificity of 96% and sensitivity of 67%, with a false-negative rate of 33% for not identifying the unilateral hearing loss, and a false-positive rate of 4%. Conclusion: The questionnaire used has shown to be feasible and relevant to actions of the community health agents of the Family Health Strategy program, with high specificity and moderate sensitivity. The use of the validated instrument should be considered to complement Newborn Hearing Screening Programs, in order to identify late onset or acquired hearing loss.

Hepatocyte nuclear factors 1α/4α and forkhead box A2 regulate the solute carrier 2A2 (Slc2a2) gene expression in the liver and kidney of diabetic rats

AIMS: Solute carrier 2a2 (Slc2a2) gene codifies the glucose transporter GLUT2, a key protein for glucose flux in hepatocytes and renal epithelial cells of proximal tubule. In diabetes mellitus, hepatic and tubular glucose output has been related to Slc2a2/GLUT2 overexpression; and controlling the expression of this gene may be an important adjuvant way to improve glycemic homeostasis. Thus, the present study investigated transcriptional mechanisms involved in the diabetes-induced overexpression of the Slc2a2 gene. MAIN METHODS: Hepatocyte nuclear factors 1α and 4α (HNF-1α and HNF-4α), forkhead box A2 (FOXA2), sterol regulatory element binding protein-1c (SREBP-1c) and the CCAAT-enhancer-binding protein (C/EBPβ) mRNA expression (RT-PCR) and binding activity into the Slc2a2 promoter (electrophoretic mobility assay) were analyzed in the liver and kidney of diabetic and 6-day insulin-treated diabetic rats. KEY FINDINGS: Slc2a2/GLUT2 expression increased by more than 50% (P<0.001) in the liver and kidney of diabetic rats, and 6-day insulin treatment restores these values to those observed in non-diabetic animals. Similarly, the mRNA expression and the binding activity of HNF-1α, HNF-4α and FOXA2 increased by 50 to 100% (P<0.05 to P<0.001), also returning to values of non-diabetic rats after insulin treatment. Neither the Srebf1 and Cebpb mRNA expression, nor the SREBP-1c and C/EBP-β binding activity was altered in diabetic rats. SIGNIFICANCE: HNF-1α, HNF-4α and FOXA2 transcriptional factors are involved in diabetes-induced overexpression of Slc2a2 gene in the liver and kidney. These data point out that these transcriptional factors are important targets to control GLUT2 expression in these tissues, which can contribute to glycemic homeostasis in diabetes.

Norm and difference : Stone Age dietary practice in the Baltic region

Stone Age research on Northern Europe frequently makes gross generalizations about the Mesolithic and Neolithic, although we still lack much basic knowledge on how the people lived. The transition from the Mesolithic to the Neolithic in Europe has been described as a radical shift from an economy dominated by marine resources to one solely dependent on farming. Both the occurrence and the geographical extent of such a drastic shift can be questioned, however. It is therefore important to start out at a more detailed level of evidence in order to present the overall picture, and to account for the variability even in such regional or chronological overviews. Fifteen Stone Age sites were included in this study, ranging chronologically from the Early Mesolithic to the Middle or Late Neolithic, c. 8300–2500 BC, and stretching geographically from the westernmost coast of Sweden to the easternmost part of Latvia within the confines of latitudes 55–59° N. The most prominent sites in terms of the number of human and faunal samples analysed are Zvejnieki, Västerbjers and Skateholm I–II. Human and faunal skeletal remains were subjected to stable carbon and nitrogen isotope analysis to study diet and ecology at the sites. Stable isotope analyses of human remains provide quantitative information on the relative importance of various food sources, an important addition to the qualitative data supplied by certain artefacts and structures or by faunal or botanical remains. A vast number of new radiocarbon dates were also obtained. In conclusion, a rich diversity in Stone Age dietary practice in the Baltic Region was demonstrated. Evidence ranging from the Early Mesolithic to the Late Neolithic show that neither chronology nor location alone can account for this variety, but that there are inevitably cultural factors as well. Food habits are culturally governed, and therefore we cannot automatically assume that people at similar sites will have the same diet. Stable isotope studies are very important here, since they tell us what people actually consumed, not only what was available, or what one single meal contained. We should not be deceived in inferring diet from ritually deposited remains, since things that were mentally important were not always important in daily life. Thus, although a ritual and symbolic norm may emphasize certain food categories, these may in fact contribute very little to the diet. By the progress of analysis of intra-individual variation, new data on life history changes have been produced, revealing mobility patterns, breastfeeding behaviour and certain dietary transitions. The inclusion of faunal data has proved invaluable for understanding the stable isotope ecology of a site, and thereby improve the precision of the interpretations of human stable isotope data. The special case of dogs, though, demonstrates that these animals are not useful for inferring human diet, since, due to the number of roles they possess in human society, dogs could deviate significantly from humans in their diet, and in several cases have been proved to do so. When evaluating radiocarbon data derived from human and animal remains from the Pitted-Ware site of Västerbjers on Gotland, the importance of establishing the stable isotope ecology of the site before making deductions on reservoir effects was further demonstrated. The main aim of this thesis has been to demonstrate the variation and diversity in human practices, challenging the view of a “monolithic” Stone Age. By looking at individuals and not only at populations, the whole range of human behaviour has been accounted for, also revealing discrepancies between norm and practice, which are frequently visible both in the archaeological record and in present-day human behaviour.