Meal-feeding scheme: twenty years of research in Brazil

Naomi Shinomiya Hell was the first researcher to investigate the physiological adaptations to a meal-feeding scheme (MFS) in Brazil. Over a period of 20 years, from 1979 to 1999, Naomi's group determined the physiological and metabolic adaptations induced by this feeding scheme in rats. The group showed the persistence of such adaptations even when MFS is associated with moderate exercise training and the performance to a session of intense physical effort. The metabolic changes induced by the feeding training were discriminated from those caused by the effective fasting period. Naomi made an important contribution to the understanding of the MFS but a lot still has to be done. One crucial question still remains to be satisfactorily answered: what is the ideal control for the MFS?

Air pollution and neonatal deaths in São Paulo, Brazil

Air pollution has been associated with health effects on different age groups. The present study was designed to assess the impact of daily changes in air pollutants (NO2, SO2, CO, O3, and particle matter (PM10)) on total number of daily neonatal deaths (those that occur between the first and the 28th days of life) in São Paulo, from January 1998 to December 2000, since adverse outcomes such as neonatal deaths associated with air pollution in Brazil have not been evaluated before. Generalized additive Poisson regression models were used and nonparametric smooth functions (loess) were adopted to control long-term trend, temperature, humidity, and short-term trends. A linear term was used for holidays. The association between air pollutants and neonatal deaths showed a short time lag. Interquartile range increases in PM10 (23.3 µg/m³) and SO2 (9.2 µg/m³) were associated with increases of 4% (95% CI, 2-6) and 6% (95% CI, 4-8), respectively. Instead of adopting a two-pollutant model we created an index to represent PM10 and SO2 effects. For an interquartile range increase in the index an increase of 6.3% (95% CI, 6.1-6.5) in neonatal deaths was observed. These results agree with previous studies performed by our group showing the deleterious effects of air pollutants during the perinatal period. The method reported here represents an alternative approach to analyze the relationship between highly correlated pollutants and public health problems, reinforcing the idea of the synergic effects of air pollutants in public health.

Temperature, air pollution, and mortality from myocardial infarction in São Paulo, Brazil

An increase in daily mortality from myocardial infarction has been observed in association with meteorological factors and air pollution in several cities in the world, mainly in the northern hemisphere. The objective of the present study was to analyze the independent effects of environmental variables on daily counts of death from myocardial infarction in a subtropical region in South America. We used the robust Poisson regression to investigate associations between weather (temperature, humidity and barometric pressure), air pollution (sulfur dioxide, carbon monoxide, and inhalable particulate), and the daily death counts attributed to myocardial infarction in the city of São Paulo in Brazil, where 12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a linear fashion for relative humidity and day-of-week, while nonparametric smoothing factors were used for seasonal trend and temperature. We found a significant association of daily temperature with deaths due to myocardial infarction (P < 0.001), with the lowest mortality being observed at temperatures between 21.6 and 22.6ºC. Relative humidity appeared to exert a protective effect. Sulfur dioxide concentrations correlated linearly with myocardial infarction deaths, increasing the number of fatal events by 3.4% (relative risk of 1.03; 95% confidence interval = 1.02-1.05) for each 10 µg/m³ increase. In conclusion, this study provides evidence of important associations between daily temperature and air pollution and mortality from myocardial infarction in a subtropical region, even after a comprehensive control for confounding factors.

Epidemiological studies in the information and genomics era: experience of the Clinical Genome of Cancer Project in São Paulo, Brazil

Genomics is expanding the horizons of epidemiology, providing a new dimension for classical epidemiological studies and inspiring the development of large-scale multicenter studies with the statistical power necessary for the assessment of gene-gene and gene-environment interactions in cancer etiology and prognosis. This paper describes the methodology of the Clinical Genome of Cancer Project in São Paulo, Brazil (CGCP), which includes patients with nine types of tumors and controls. Three major epidemiological designs were used to reach specific objectives: cross-sectional studies to examine gene expression, case-control studies to evaluate etiological factors, and follow-up studies to analyze genetic profiles in prognosis. The clinical groups included patients' data in the electronic database through the Internet. Two approaches were used for data quality control: continuous data evaluation and data entry consistency. A total of 1749 cases and 1509 controls were entered into the CGCP database from the first trimester of 2002 to the end of 2004. Continuous evaluation showed that, for all tumors taken together, only 0.5% of the general form fields still included potential inconsistencies by the end of 2004. Regarding data entry consistency, the highest percentage of errors (11.8%) was observed for the follow-up form, followed by 6.7% for the clinical form, 4.0% for the general form, and only 1.1% for the pathology form. Good data quality is required for their transformation into useful information for clinical application and for preventive measures. The use of the Internet for communication among researchers and for data entry is perhaps the most innovative feature of the CGCP. The monitoring of patients' data guaranteed their quality.

Prevalence of hepatitis C virus (HCV) infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil

Hepatitis C virus (HCV) infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD), despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3) (Murex anti-HCV, Abbott Murex, Chicago, IL, USA). Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2%). HCV-RNA was detected in 92/125 (73.6%) of the anti-HCV-positive patients. HCV genotype 1 (77.9%) was the most prevalent, followed by genotype 3 (10.5%) and genotype 2 (4.6%). Mixed infections of genotypes 1 and 3 were found in 7.0% of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

Chronic obstructive pulmonary disease is underdiagnosed and undertreated in São Paulo (Brazil): results of the PLATINO study

Chronic obstructive pulmonary disease (COPD) is a common disease in adults over 40 years of age and has a great social and economic impact. It remains little recognized and undertreated even in developed countries. However, there are no data about its diagnosis and treatment in Brazil. The objectives of the present study were to evaluate the proportion of COPD patients who had never been diagnosed and to determine if the COPD patients who had been identified were receiving appropriate treatment. The Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) was a randomized epidemiological study of adults over 40 years living in five metropolitan areas, including São Paulo. The studied sample was randomly selected from the population after a division of the metropolitan area of São Paulo in clusters according to social characteristics. All subjects answered a standardized questionnaire on respiratory symptoms, history of smoking, previous diagnosis of lung disease, and treatments. All subjects performed spirometry. The criterion for the diagnosis of COPD was defined by a post-bronchodilator FEV1/FVC ratio lower than 0.7. A total of 918 subjects were evaluated and 144 (15.8%) met the diagnostic criterion for COPD. However, 126 individuals (87.5%) had never been diagnosed. This undiagnosed group of COPD patients had a lower proportion of subjects with respiratory symptoms than the previously diagnosed patients (88.9 vs 54.8%) and showed better lung function with greater FEV1 (86.8 ± 20.8 vs 68.5 ± 23.6% predicted) and FVC (106.6 ± 22.4 vs 92.0 ± 24.1% predicted). Among the COPD patients, only 57.3% were advised to stop smoking and 30.6% received the influenza vaccine. In addition, 82.3% did not receive any pharmacological treatment. In conclusion, COPD is underdiagnosed and a large number of COPD patients are not treated appropriately.

Sleep habits and complaints of adults in the city of São Paulo, Brazil, in 1987 and 1995

This study compares the prevalence of complaints of insomnia, excessive diurnal sleepiness, parasomnias, and sleep habits of the adult population in the city of São Paulo, Brazil, estimated in surveys carried out in 1987 and 1995. Representative samples of 1000 adult residents per survey were interviewed using a validated structured sleep questionnaire, the "UNIFESP Sleep Questionnaire". Difficulty maintaining sleep, difficulty initiating sleep and early morning awakening, occurring at least three times a week, were reported in 1987 and 1995, by 15.8/27.6, 13.9/19.1, and 10.6/14.2% of the interviewees, respectively, significantly increasing throughout time. These sleep problems were more often found among women. Frequencies of excessive diurnal sleepiness and sleep attacks were unchanged comparing 1987 with 1995 (4.5 vs 3.8 and 3.1 vs 3.0%, respectively). Parasomnia complaints remained unchanged, with the exception of leg cramps, which doubled in prevalence from 1987 to 1995 (2.6 to 5.8%). Snoring was the most common parasomnia (21.5% in 1995), reported more often by men than by women, and somnambulism was the least common (approximately 1%). Besides sleeping slightly less, interviewees went to bed and woke up later in 1995. Approximately 12% of the subjects in both surveys had consulted a physician due to sleep problems and 3.0% reported habitual use of sleep-promoting substances in 1995. Overall, there was a significant increase in insomnia complaints from 1987 to 1995 in the general population of the city of São Paulo. This major change over a little under a decade should be considered as an important public health issue.

Prevalence of diphtheria and tetanus antibodies and circulation of Corynebacterium diphtheriae in São Paulo, Brazil

The introduction of routine vaccination against tetanus and diphtheria in Brazil has decreased the incidence and changed the epidemiology of both diseases. We then investigated the prevalence of Corynebacterium diphtheriae carrier status and diphtheria and tetanus immunity in São Paulo, Brazil. From November 2001 to March 2003, 374 individuals were tested for the presence of C. diphtheriae in the naso-oropharynx and of serum diphtheria and tetanus antibodies. Participants were all healthy individuals without acute or chronic pathologies and they were stratified by age as follows: 0-12 months and 1-4, 5-9, 10-14, 15-24, 25-39, 40-59, and ³60 years. Antibodies were assessed using a double-antigen ELISA. C. diphtheriae species were identified by biochemical analysis and toxigenicity was assessed by the Elek test. For diphtheria, full protection (antibodies ³0.1 IU/mL) was present in 84% of the individuals, 15% had basic protection (antibodies ³0.01 and <0.1 IU/mL) and 1% were susceptible (antibodies <0.01 IU/mL). Full tetanus protection (antibodies ³0.1 IU/mL) was present in 79% of the participants, 18% had basic protection (antibodies ³0.01 and <0.1 IU/mL) and 3% were susceptible (antibodies <0.01 IU/mL). The geometric mean of diphtheria and tetanus antibodies reached the highest values at 5-9 years and decreased until the 40-59-year age range, increasing again in individuals over 60 years. Three participants (0.8%) were carriers of C. diphtheriae, all non-toxigenic strains. The present results demonstrate the clear need of periodic booster for tetanus and diphtheria vaccine in adolescents and adults after primary immunization in childhood.

Effect of air pollution on diabetes and cardiovascular diseases in São Paulo, Brazil

Type 2 diabetes increases the risk of cardiovascular mortality and these patients, even without previous myocardial infarction, run the risk of fatal coronary heart disease similar to non-diabetic patients surviving myocardial infarction. There is evidence showing that particulate matter air pollution is associated with increases in cardiopulmonary morbidity and mortality. The present study was carried out to evaluate the effect of diabetes mellitus on the association of air pollution with cardiovascular emergency room visits in a tertiary referral hospital in the city of São Paulo. Using a time-series approach, and adopting generalized linear Poisson regression models, we assessed the effect of daily variations in PM10, CO, NO2, SO2, and O3 on the daily number of emergency room visits for cardiovascular diseases in diabetic and non-diabetic patients from 2001 to 2003. A semi-parametric smoother (natural spline) was adopted to control long-term trends, linear term seasonal usage and weather variables. In this period, 45,000 cardiovascular emergency room visits were registered. The observed increase in interquartile range within the 2-day moving average of 8.0 µg/m³ SO2 was associated with 7.0% (95%CI: 4.0-11.0) and 20.0% (95%CI: 5.0-44.0) increases in cardiovascular disease emergency room visits by non-diabetic and diabetic groups, respectively. These data indicate that air pollution causes an increase of cardiovascular emergency room visits, and that diabetic patients are extremely susceptible to the adverse effects of air pollution on their health conditions.

Ethnicity as a risk factor for obstructive sleep apnea: comparison of Japanese descendants and white males in São Paulo, Brazil

Some studies showed that Asians with obstructive sleep apnea (OSA) are thinner than Caucasians. Because obesity is a major risk factor for OSA, it was concluded that Asians are predisposed to OSA. However, body fat composition varies for a same body mass index (BMI) according to ethnicity. We firstly compared anthropometric characteristics, symptoms and associated disorders in all consecutive male Japanese descendants and white males with OSA referred for polysomnography. In a second analysis, all Japanese descendants were compared to a subgroup of white males, matched for apnea/hypopnea index and age. In the first analysis, age, symptoms, OSA severity and co-morbidities were similar among Japanese descendants (N = 54) and white patients (N = 466). However, Japanese descendants had a lower BMI than white patients: 27.1 (25.5-28.4) vs 29.4 (26.5-33.0) kg/m², respectively (P < 0.001). In the second analysis, Japanese descendants had a lower BMI than white patients (P < 0.001). Multiple linear regression considering the entire group revealed that age, BMI, neck circumference, Epworth sleepiness scale, ethnicity and %REM sleep were independent predictors for apnea/hypopnea index (P < 0.001). Ethnicity was no longer significantly associated with OSA severity when we adopted the World Health Organization criteria for obesity (≥25 and 30 kg/m² among Japanese descendants and white males, respectively). Japanese descendants with OSA have a lower BMI than white subjects of similar severity. However, ethnicity was not associated with OSA severity when an ethnical difference in obesity criteria was respected. Our data suggest that Japanese descendants are not predisposed to OSA.

Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil

Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3% males and 30.7% females) aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany). Most (63%) unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71%) of young military donors (18 to 30 years) were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50% of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64% of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL) independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL) than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05). In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

Citations to papers from Brazilian institutions: a more effective indicator to assess productivity and the impact of research in graduate programs

A recent assessment of 4400 postgraduate courses in Brazil by CAPES (a federal government agency dedicated to the improvement of the quality of and research at the postgraduate level) stimulated a large amount of manifestations in the press, scientific journals and scientific congresses. This gigantic effort to classify 16,400 scientific journals in order to provide indicators for assessment proved to be puzzling and methodologically erroneous in terms of gauging the institutions from a metric point of view. A simple algorithm is proposed here to weigh the scientometric indicators that should be considered in the assessment of a scientific institution. I conclude here that the simple gauge of the total number of citations accounts for both the productivity of scientists and the impact of articles. The effort spent in this exercise is relatively small, and the sources of information are fully accessible. As an exercise to estimate the value of the methodology, 12 institutions of physics (10 from Brazil, one from the USA and one from Italy) have been evaluated.

Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival

The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

Cancer research in Brazil - stuck in second gear?

This article describes the main issues regarding clinical cancer research in Brazil, including both the opportunities and the hurdles. Scientists and clinicians in this field had the opportunity to talk to regulatory agencies and to the Health Ministry representative at a meeting held in the State of Rio de Janeiro, Brazil, in April 2014. Our conclusions are that we do indeed have opportunities; however, we need to move forward regarding partnerships between academia and industry, increase the availability of funding, and provide easier navigation through the regulatory processes.

Drivers and barriers to digital television adoption in Portugal: the perspectives of the TV viewers and other main stakeholders

To understand what are the most significant factors for digital TV adoption by the Portuguese population in the switchover context is the main goal of the research project here presented. In April 26, 2012, the analogue terrestrial television switchoff is planned to occur in Portugal, according to the schedule published by the national telecommunication regulator Anacom. Digital terrestrial TV was launched in the country in April 2009, making Portugal one of the countries with a more ambitious schedule – or risky, depending on the perspective - for the full transition from analogue to digital terrestrial television. In this paper we will start by presenting the research project’s objectives, theoretical framework and research design. Next, we will present first results of the project focused on the barriers and drivers to digital TV adoption from two of the empirical studies which integrate it, namely, the quantitative inquiry administered to a representative sample of the Portuguese population and interviews with main stakeholders in the area of digital TV in Portugal. The perspectives of the television viewers are compared with other main stakeholders in this process. The paper will be concluded with a brief discussion of these results and a brief enumeration of next steps for the project.