Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

Engagement of multifocal neural circuits during recall of autobiographical happy events

Happy emotional states have not been extensively explored in functional magnetic resonance imaging studies using autobiographic recall paradigms. We investigated the brain circuitry engaged during induction of happiness by standardized script-driven autobiographical recall in 11 healthy subjects (6 males), aged 32.4 ± 7.2 years, without physical or psychiatric disorders, selected according to their ability to vividly recall personal experiences. Blood oxygen level-dependent (BOLD) changes were recorded during auditory presentation of personal scripts of happiness, neutral content and negative emotional content (irritability). The same uniform structure was used for the cueing narratives of both emotionally salient and neutral conditions, in order to decrease the variability of findings. In the happiness relative to the neutral condition, there was an increased BOLD signal in the left dorsal prefrontal cortex and anterior insula, thalamus bilaterally, left hypothalamus, left anterior cingulate gyrus, and midportions of the left middle temporal gyrus (P < 0.05, corrected for multiple comparisons). Relative to the irritability condition, the happiness condition showed increased activity in the left insula, thalamus and hypothalamus, and in anterior and midportions of the inferior and middle temporal gyri bilaterally (P < 0.05, corrected), varying in size between 13 and 64 voxels. Findings of happiness-related increased activity in prefrontal and subcortical regions extend the results of previous functional imaging studies of autobiographical recall. The BOLD signal changes identified reflect general aspects of emotional processing, emotional control, and the processing of sensory and bodily signals associated with internally generated feelings of happiness. These results reinforce the notion that happiness induction engages a wide network of brain regions.

Cognitive performance of young and elderly subjects on the free word recall memory test: effect of presentation order on recall order

The influence of aging on memory has been extensively studied, but the importance of short-term memory and recall sequence has not. The objective of the current study was to examine the recall order of words presented on lists and to determine if age affects recall sequence. Physically and psychologically healthy male subjects were divided into two groups according to age, i.e., 23 young subjects (20 to 30 years) and 50 elderly subjects (60 to 70 years) submitted to the Wechsler Adult Intelligence Scale-Revised and the free word recall test. The order of word presentation significantly affected the 3rd and 4th words recalled (P < 0.01; F = 14.6). In addition, there was interaction between the presentation order and the type of list presented (P < 0.05; F = 9.7). Also, both groups recalled the last words presented from each list (words 13-15) significantly more times 3rd and 4th than words presented in all remaining positions (P < 0.01). The order of word presentation also significantly affected the 5th and 6th words recalled (P = 0.05; F = 7.5) and there was a significant interaction between the order of presentation and the type of list presented (P < 0.01; F = 20.8). The more developed the cognitive functions, resulting mainly from formal education, the greater the cognitive reserve, helping to minimize the effects of aging on the long-term memory (episodic declarative).

Tracking of physical activity from adolescence to adulthood: a population-based study

OBJECTIVE: To assess the association between regular physical activity in adolescence and leisure-time physical activity in adulthood, with emphasis on gender differences. METHODS: A population-based cross-sectional study was carried out in Pelotas, Southern Brazil, in 2003. A representative sample of households was selected in multiple stages and subjects aged 20-59 years were interviewed. Leisure-time physical activity was evaluated using the International Physical Activity Questionnaire. Data on adolescent physical activity were based on subjects' recall. RESULTS: Of 2,577 subjects interviewed, 27.5% were classified as adequately active, and 54.9% reported regular physical activity in adolescence. Subjects who engaged in regular physical activity during adolescence were more likely to be adequately active in adulthood (adjusted prevalence ratio 1.42; 95% CI: 1.23; 1.65). This effect was stronger in women (adjusted prevalence ratio: 1.51; 95% CI: 1.22; 1.86) than men (adjusted prevalence ratio: 1.35; 95% CI: 1.10; 1.67). CONCLUSIONS: Promoting physical activity in school age may be a successful intervention against the epidemic of adult inactivity. Although women were less likely to report regular physical activity in adolescence, the effect of this experience on adult behavior was stronger than in men.

Agreement between data obtained from repeated interviews with a six-years interval

The objective of the study was to compare information collected through face-to-face interviews at first time and six years later in a city of Southeastern Brazil. In 1998, 32 mothers (N=32) of children aged 20 to 30 months answered a face-to-face interview with structured questions regarding their children's brushing habits. Six years later this same interview was repeated with the same mothers. Both interviews were compared for overall agreement, kappa and weighted kappa. Overall agreement between both interviews varied from 41 to 96%. Kappa values ranged from 0.00 to 0.65 (very bad to good) without any significant differences. The results showed lack of agreement when the same interview is conducted six years later, showing that the recall bias can be a methodological problem of interviews.

Trans fatty acid intake among the population of the city of São Paulo, Brazil

OBJECTIVE: To analyze the monounsaturated and polyunsaturated trans fatty acid intake among the general population. METHODS: A cross-sectional study was conducted in São Paulo, Southeastern Brazil, in 2003, on a representative sample of 2,298 male and female subjects, including 803 adolescents (12 to 19 years), 713 adults (20 to 59 years) and 782 elderly people (60 years or over). Food intake was measured using 24-hour recall. Mean trans fatty acid intake was described according to gender and age group. RESULTS: The mean trans fatty acid intake was 5.0 g/day (SE = 0.1), accounting for 2.4% (SE = 0.1) of total energy and 6.8% (SE = 0.1) of total lipids. The adolescents had the highest mean intake levels (7.4 g/day; 2.9% of energy) while the adults and the elderly had similar intake (2.2% of energy for both; 6.4% of lipids and 6.5% of lipids, respectively). The mean trans fatty acid intake among adult and elderly women (approximately 2.5% of energy and 7.0% of lipids) was higher than among men in the same age group. The food item with the highest contribution towards trans fatty acids was margarine, accounting for more than 30% of total intake, followed by filled cookies among adolescents and meat among adults and the elderly. CONCLUSIONS: The trans fatty acid intake is above the level recommended by the World Health Organization. Replacement of the trans fatty acids in manufactured food items may be an effective measure for reducing trans fatty acid intake in Brazil.

Factors associated to medicine use among children from the 2004 Pelotas Birth Cohort (Brazil)

OBJECTIVE: To identify factors associated to medicine use among children from the 2004 Pelotas Birth Cohort, Brazil. METHODS: Prospective study to evaluate medicine use in children aged 3, 12 and 24 months regardless of the reasons, therapeutic indication or class. The study included 3,985 children followed up at three months of age, 3,907 at 12 months, and 3,868 at the last follow-up time of 24 months. Mothers were interviewed to collect information on medicine use during the recall period of 15 days prior to the interview. The outcome was studied according to sociodemographic and perinatal variables, mother's perception of child's health and breastfeeding status. Crude and adjusted analyses were performed by Poisson regression following a hierarchical model. RESULTS: The prevalence of medicine use ranged from 55% to 65% in the three follow-ups. After controlling for confounders, some variables remained associated to medicine use only at the three-month follow-up with greatest use among children of younger mothers, those children who had intrapartum complications, low birthweight, were never breastfed and were admitted to a hospital. Greatest medicine use was also associated with being a firstborn child at 3 and 12 months; mother's perception of their child health as fair or poor and children whose mothers have private health insurance at 12 and 24 months; highest maternal education level at all follow-up times. CONCLUSIONS: Different variables influence medicine use among children during the first two years of life and they change as the child ages especially maternal factors and those associated to the child's health problems.

Prevalence of self-medication in the adult population of Brazil: a systematic review

OBJECTIVE To evaluate the prevalence of self-medication in Brazil’s adult population.METHODS Systematic review of cross-sectional population-based studies. The following databases were used: Medline, Embase, Scopus, ISI, CINAHL, Cochrane Library, CRD, Lilacs, SciELO, the Banco de teses brasileiras(Brazilian theses database) (Capes) and files from the Portal Domínio Público (Brazilian Public Domain). In addition, the reference lists from relevant studies were examined to identify potentially eligible articles. There were no applied restrictions in terms of the publication date, language or publication status. Data related to publication, population, methods and prevalence of self-medication were extracted by three independent researchers. Methodological quality was assessed following eight criteria related to sampling, measurement and presentation of results. The prevalences were measured from participants who used at least one medication during the recall period of the studies.RESULTS The literature screening identified 2,778 records, from which 12 were included for analysis. Most studies were conducted in the Southeastern region of Brazil, after 2000 and with a 15-day recall period. Only five studies achieved high methodological quality, of which one study had a 7-day recall period, in which the prevalence of self-medication was 22.9% (95%CI 14.6;33.9). The prevalence of self-medication in three studies of high methodological quality with a 15-day recall period was 35.0% (95%CI 29.0;40.0, I2 = 83.9%) in the adult Brazilian population.CONCLUSIONS Despite differences in the methodologies of the included studies, the results of this systematic review indicate that a significant proportion of the adult Brazilian population self-medicates. It is suggested that future research projects that assess self-medication in Brazil standardize their methods.

ERICA: intake of macro and micronutrients of Brazilian adolescents

ABSTRACT OBJECTIVE To describe food and macronutrient intake profile and estimate the prevalence of inadequate micronutrient intake of Brazilian adolescents. METHODS Data from 71,791 adolescents aged from 12 to 17 years were evaluated in the 2013-2014 Brazilian Study of Cardiovascular Risks in Adolescents (ERICA). Food intake was estimated using 24-hour dietary recall (24-HDR). A second 24-HDR was collected in a subsample of the adolescents to estimate within-person variability and calculate the usual individual intake. The prevalence of food/food group intake reported by the adolescents was also estimated. For sodium, the prevalence of inadequate intake was estimated based on the Tolerable Upper Intake Level (UL). The Estimated Average Requirement (EAR) method used as cutoff was applied to estimate the prevalence of inadequate nutrient intake. All the analyses were stratified according to sex, age group and Brazilian macro-regions. All statistical analyses accounted for the sample weight and the complex sampling design. RESULTS Rice, beans and other legume, juice and fruit drinks, breads and meat were the most consumed foods among the adolescents. The average energy intake ranged from 2,036 kcal (girls aged from 12 to 13 years) to 2,582 kcal (boy aged from14 to 17 years). Saturated fat and free sugar intake were above the maximum limit recommended (< 10.0%). Vitamins A and E, and calcium were the micronutrients with the highest prevalence of inadequate intake (> 50.0%). Sodium intake was above the UL for more than 80.0% of the adolescents. CONCLUSIONS The diets of Brazilian adolescents were characterized by the intake of traditional Brazilian food, such as rice and beans, as well as by high intake of sugar through sweetened beverages and processed foods. This food pattern was associated with an excessive intake of sodium, saturated fatty acids and free sugar.

Response rate in the Study of Cardiovascular Risks in Adolescents – ERICA

ABSTRACT OBJECTIVE To describe the response rate and characteristics of people who either took part or not in from the Study of Cardiovascular Risks in Adolescents (ERICA) , according to information subsets. METHODS ERICA is a school-based, nation-wide investigation with a representative sample of 12 to 17-year-old adolescents attending public or private schools in municipalities with over 100,000 inhabitants in Brazil. Response rate of eligible subjects were calculated according to macro-regions, sex, age, and type of school (public or private). We also calculated the percentages of replacement schools in comparison with the ones originally selected as per the sample design, according to the types of schools in the macro-regions. The subjects and non-subjects were compared according to sex, age, and average body mass indices (kg/m2). RESULTS We had 102,327 eligible adolescents enrolled in the groups drawn. The highest percentage of complete information was obtained for the subset of the questionnaire (72.9%). Complete information regarding anthropometric measurements and the ones from the questionnaire were obtained for 72.0% of the adolescents, and the combination of these data with the 24-hour dietary recall were obtained for 70.3% of the adolescents. Complete information from the questionnaire plus biochemical blood evaluation data were obtained for 52.5% of the morning session adolescents (selected for blood tests). The response percentage in private schools was higher than the one in public schools for most of the combination of information. The ratio of older and male adolescents non-participants was higher than the ratio among participants. CONCLUSIONS The response rate for non-invasive procedures was high. The response rate for blood collection – an invasive procedure that requires a 12-hour fasting period and the informed consent form from legal guardians – was lower. The response rate observed in public schools was lower than in the private ones, and that may reflect lower school frequency of registered students.

Treatment of relapsing chronic infections of the respiratory tract: a comparative study of the effectiveness of non specific immunotherapy with the immunoadjuvant p40 and of vaccinotherapy

The treatment of relapsing chronic infections (RCI) encounters many difficulties. In the present study, the use of the immuno adjuvant P40 either alone or in association with vaccinotherapy for the treatment of RCI turned out to be very effective, whereas vaccinotherapy alone was not. It is hypothesized that cell-mediated immunity may play a major role in controlling RCI, since the clinical improvement of the patients kept up with the positivation of previously negative skin tests carried out with either the specific infecting agent or with recall-anti gens.

Immunopathology of human schistosomiasis mansoni: I. Immunomodulatory influences on T cell function

Cell mediated immune response was studied in patients with recent and chronic Schistosoma mansoni infection. Precultured peripheral mononuclear cells showed significantly higher responses to S. mansoni adult worm antigen (SAWA) when compared to fresh cell preparations. The addition of each patient serum to the precultured cells reactions to SAWA or recall antigens demonstrated a strong inhibitory serum action, which was also noted on allogeneic cells derived from healthy subjects. The CD4 subset was the main responding cell to SAWA being this reactivity highly suppressed by the presence of the monocyte macrophage accessory cells. We stressed the simultaneous inhibitory action of humoral and cellular factors on the specific cell response to S. mansoni.

Subcutaneous immunization against Leishmania major - infection in mice: efficacy of formalin-killed promastigotes combined with adjuvants

Formalin-killed promastigotes (FKP) of Leishmania major, in combination with Montanide ISA 720 (MISA), BCG or alum were used in vaccination of an inbred murine model against cutaneous leishmaniasis (CL). Significant and specific increases in anti-FKP IgG responses were detected for both alum-FKP and BCG-FKP compared to MISA-FKP (p < 0.001). Significant increases in splenic lymphocyte recall proliferation was obtained in the MISA-FKP vaccinated mice compared to alum-FKP or BCG-FKP vaccinated groups (p < 0.01). The highest interferon-γ responses were observed in the BCG-FKP group followed by the MISA-FKP while the alum-FKP gave the least responses. Significantly reduced lesion sizes were obtained in the MISA-FKP group compared to the BCG/alum adjuvants-FKP vaccinated groups. Although the BCG-FKP group showed the highest IFN-γ responses, it failed to control cutaneous lesions. Significant reductions in parasite numbers were observed in the MISA-FKP and BCG-FKP vaccinated groups (p < 0.001). There was a good correlation between parasite burden and IFN-γ level indicating IFN-γ response as a sensitive parameter of the immune status. In conclusion, MISA-FKP is the most efficacious vaccine formulation against murine cutaneous leishmaniasis.

T cell-dependent immunodepression in vivo in Schistosoma mansoni infected patients

T-cell function was evaluated in 29 patients with either hepatointestinal or hepatosplenic schistosomiasis by intradermal tests to recall antigens. Immunodepression was detected in 26% of the subjects with hepatointestinal schistosomiasis and in 50% of those with the hepatosplenic form. Cellular immunodepression was related to worm load and spleen size. This non specific T-cell immunodepression may represent a serious constraint to the elimination of intracellular pathogens both in hepatosplenic or hepatointestinal schistosomiasis.

Specific treatment of hepatosplenic schistosomiasis can increase T-lymphocyte reactivity

It has been recognized that Schistosoma mansoni infection causes depression of T-cell responsiveness. In this study we have evaluated whether immunodepression associated to schistosomiasis could be reverted by specific treatment. T-cell immune response was assessed by means of intradermal tests using recall antigens in a group of 22 patients with hepatosplenic schistosomiasis, one year after treatment with oxamniquine and compared with a group of untreated hepatosplenic patients. Only 27% of treated patients presented complete anergy to all tested antigens, in marked contrast to 80% unresponsiveness showed by hepatosplenic patients without treatment. Although most of the treated individuals showed some response to the tested antigens, in some individuals this unresponsiveness still persisted after treatment. Anergy was not found in any normal individual of the control group. It was concluded that Schistosoma mansoni infected patients may recover their normal immune responsiveness after the elimination of the worm by treatment