Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Glutathione peroxidase and glutathione S-transferase in blood and liver from a hypoxia-tolerant fish under oxygen deprivation.

Liver enzyme activities can be employed as biomarkers, but liver can only be obtained with death of the specimen. On the other hand, blood withdrawal is a non-lethal procedure. Accordingly, the hypothesis of this study is to verify if glutathione peroxidase (GPX) and glutathione S-transferase (GST) activities in blood parallel those in the liver of the hypoxia-tolerant fish, Piaractus mesopotamicus (pacu), submitted to hypoxia conditions. GPX was assayed with H2O2 in cytosols from both liver and erythrocytes and exhibited no significant variation, either in erythrocytes or in liver, when comparing pacus under normoxia with those under hypoxia (42 h). GST activity with chloro-dinitrobenzene (CDNB), an artificial substrate suitable for almost all GST isoenzymes, was compared to activity with 4-hydroxy-nonenal (4-HNE), a physiological endogenous substrate. GST activity with CDNB did not change in liver or in erythrocyte cytosols in pacus under hypoxia compared to those under normoxia. On the other hand, a significant decrease in erythrocyte activity with 4-HNE was observed after 42 h of hypoxia in both erythrocytes and liver, which may be a response to increased lipid oxidation in erythrocytes. Erythrocyte GST activity was 3-fold higher with 4-HNE than with CDNB, indicating that 4-HNE is a more appropriate substrate to determine GST activity in pacu erythrocytes.

Aspectos parasitológicos da traíra (Hoplias malabaricus ) proveniente da cidade de São Bento, MA / Parasitologic aspects of traíra (Hoplias malabaricus) from the São Bento city, MA

The aim of this study was to verify the parasitologycal aspects of fish (Hoplias malabaricus), coming from São Bento city, Maranhão state. For this, 70 fish were used, verifying the parasitism indexes and coefficients. For the parasitological results nematodeos were identified, with zoonotical potential of the Contracaecum spp, Pseudoterranova spp, Eustrongylides spp; monogenetics Gyrodactirus spp, Dactylogirus spp and larva Acanthella of Acanthocephalo. Of the 70 (100%) fishes, 64 (91.4%) were sponged, with prevalence of 82.8% (58) for the nematodeo Contracaecum spp, 65.7% (46), Pseudoterranova spp, 7.1% (5), Eustrongylides spp, 71.4% (50), monogenetics and larva Acanthella of Acantocephalo, respectively. A maior amplitude de intensidade (1-30), coeficiente de variação foi verificado para o nematódeo Pseudoterranova spp., a intensidade média (7,3), índice de abundância (6,7), coeficiente de dominância (36,4) foi ao Contacaecum spp., todos os parasitos estavam no mesentério da cavidade abdominal, encistados em forma larval.The largest intensity width (1-30), variation coefficient was verified for the nematodeo Pseudoterranova spp, the medium intensity (7,3), abundance index (6,7), dominance coefficient (36,4) it went to the Contacaecum spp, all of the parasites were in the mesenterio of the abdominal cavity, encysted in larval form. The results show that fish from this region presented unsatisfactory sanitary conditions in parasitological aspect and can expose consumers to the risks of foodborne illnesses.(AU)

Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells.

Response of phytoplankton to an experimental fish culture in net cages in a subtropical reservoir / Resposta do fitoplâncton ao cultivo experimental de peixes em tanques-rede em um reservatório subtropical

Abstract This study aimed to evaluate nutrients concentration and spatial-temporal changes in phytoplankton biovolume during an experimental fish culture in net cages in a lateral arm of Salto Caxias reservoir, Brazil. Two sampling stations were placed in the affected lateral arm and other two in a cageless lateral arm. Neither abiotic variables nor phytoplankton biovolume presented significant differences between the treatments. Only temporal changes were confirmed by the analysis performed. Both lateral arms were classified as oligotrophic, reflecting low influence of the net cages. Phytoplankton growth seems to be limited by nitrogen. Biovolume values were, in general, low and five major functional groups were recognized (E, F, G, K and P). In summer higher biovolume values were observed and representatives of Chlorophyceae and Cyanobacteria belonging to the functional groups F and K, respectively, were the most important. In winter phytoplankton was mainly composed by Bacillariophyceae taxa from P group. G group was also restricted to winter and E group occurred in winter and summer. The variations recorded in phytoplankton structure appear to have been mainly influenced by seasonal changes in temperature, precipitation and nutrients availability. The effects of net cages on the abiotic variables and phytoplankton biovolume appear to have been small, probably due to the small number of net cages employed and the system dilution capacity. However, a permanent monitoring of phytoplankton is recommended, since this environment has a carrying capacity, from which the trophic state may increase.

Resumo Este estudo objetivou avaliar alterações nas variáveis abióticas e no biovolume fitoplanctônico durante o cultivo experimental de peixes em tanques-rede em um braço lateral do reservatório de Salto Caxias, Brasil. Foram selecionadas duas estações de amostragem no braço com tanques-rede e outras duas em um braço sem tanques. As variáveis abióticas e o biovolume fitoplanctônico não apresentaram diferenças significativas entre os locais estudados. Apenas mudanças temporais foram confirmadas pelas análises utilizadas. Os dois braços laterais foram classificados como oligotróficos, refletindo a baixa influência dos tanques-rede. O crescimento do fitoplâncton parece ter sido limitado principalmente por nitrogênio. Os valores de biovolume foram, em geral, baixos e cinco principais grupos funcionais foram observados (E, F, G, K e P). No verão, os maiores valores de biovolume foram observados e representantes de Chlorophyceae e Cyanobacteria dos grupos funcionais F e K, respectivamente, se destacaram. No inverno, o fitoplâncton foi composto principalmente por táxons de Bacillariophyceae do grupo P. O grupo G também foi restrito ao inverno e o grupo E ocorreu no inverno e verão. As variações registradas na estrutura do fitoplâncton parecem ter sido principalmente influenciadas pelas mudanças sazonais de temperatura, precipitação e disponibilidade de nutrientes. Os efeitos dos tanques-rede sobre as variáveis abióticas e biovolume fitoplanctônico parecem ter sido pequenos, provavelmente devido ao pequeno número de tanques utilizados e a capacidade de diluição do sistema. Entretanto, o monitoramento permanente do fitoplâncton é recomendado, uma vez que este ambiente possui uma capacidade de suporte, a partir da qual o estado trófico pode aumentar.

Immunoexpression of HPV 16/18 E6 and E7 oncoproteins in high-grade cervical squamous intraepithelial lesions in HIV-positive women.

The aim of this study was to assess the immunoexpression of human papillomavirus genotypes 16 and 18 (E6 and E7) oncoproteins in cervical high-grade squamous intraepithelial lesions (HSIL) of human immunodeficiency virus (HIV)-positive women. These results were also compared to the persistence and/or recurrence of lesions after loop electrosurgical excision procedure. Cervical samples from 158 patients were divided into three groups according to the presence or absence of HSIL in women who were or were not HIV-positive. By using the tissue microarray technique, immunohistochemistry was performed to analyze the expression of HPV 16/18 E6 and E7 oncoproteins. Cervical samples from 95 HIV-positive women and 63 HIV-negative women were studied. A statistically significant difference was found in the immunoexpression of E6 and E7 oncoproteins in samples from HIV-positive women with HSIL and that of women with non-neoplastic tissue (P < 0.001). There was also a statistically significant correlation between the immunoexpression of E6 (P = 0.012) and E7 (P < 0.001) oncoproteins in lesion persistence among HIV-positive women. Within the limitations of this study, the immunoexpression of HPV 16/18 E6 and E7 oncoproteins may have prognostic value regarding lesion persistence in HIV-positive women.

Osteosarcoma tissues and cell lines from patients with differing serum alkaline phosphatase concentrations display minimal differences in gene expression patterns.

Serum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, although its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serum ALP concentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serum ALP concentration. No differences in gene expression patterns were noted between tumours or cell lines with differing serum ALP concentration using a gene-specific two-sample t-test. Using a more sensitive empirical Bayes procedure, defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was increased in both the tissue and cell lines of the normal ALP group. Using quantitative PCR (qPCR), differences in DCUN1D1 expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serum ALP concentrations are consistent with previous studies suggesting serum ALP concentration is not associated with intrinsic differences of osteosarcoma cells.

Schistosome infection is negatively associated with mite atopy, but not wheeze and asthma in Ghanaian schoolchildren.

BACKGROUND: Epidemiological evidence suggests that helminth infection and rural living are inversely associated with allergic disorders. OBJECTIVE: The aim of the study was to investigate the effect of helminth infections and urban versus rural residence on allergy in schoolchildren from Ghana. METHODS: In a cross-sectional study of 1385 children from urban-high socio-economic status (SES), urban-low SES and rural schools, associations between body mass index (BMI), allergen-specific IgE (sIgE), parasitic infections and allergy outcomes were analysed. Allergy outcomes were skin prick test (SPT) reactivity, reported current wheeze and asthma. RESULTS: Helminth infections were found predominantly among rural subjects, and the most common were hookworm (9.9%) and Schistosoma spp (9.5%). Being overweight was highest among urban-high SES (14.6%) compared to urban-low SES (5.5%) and rural children (8.6%). The prevalence of SPT reactivity to any allergen was 18.3%, and this was highest among rural children (21.4%) followed by urban-high SES (20.2%) and urban-low SES (10.5%) children. Overall, SPT reactivity to mite (12%) was most common. Wheeze and asthma were reported by 7.9% and 8.3%, respectively. In multivariate analyses, factors associated with mite SPT were BMI (aOR 2.43, 95% CI 1.28-4.60, P = 0.007), schistosome infection (aOR 0.15, 95% CI 0.05-0.41) and mite sIgE (aOR 7.40, 95% CI 5.62-9.73, P < 0.001) but not area. However, the association between mite IgE and SPT differed by area and was strongest among urban-high SES children (aOR = 15.58, 95% CI 7.05-34.43, P < 0.001). Compared to rural, urban-low SES area was negatively associated with current wheeze (aOR 0.41, 95% CI 0.20-0.83, P = 0.013). Both mite sIgE and mite SPT were significantly associated with current wheeze and asthma. CONCLUSION AND CLINICAL RELEVANCE: Infection with schistosomes appeared to protect against mite SPT reactivity. This needs to be confirmed in future studies, preferably in a longitudinal design where schistosome infections are treated and allergic reactions reassessed.

Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study.

BACKGROUND: Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. OBJECTIVE: To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. METHODS: A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7-19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. RESULTS: The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33-3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49-11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. CONCLUSIONS AND CLINICAL RELEVANCE: Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.

Interleukin-21 expanded NKDC in vitro reduces the B16F10 tumor growth in vivo.

Innate immunity to tumors is mediated mainly by natural killer cells (NKs) and dendritic cells (DCs). The function of these cells is coordinated by cytokines produced during the inflammatory process. NK cells are highly active against tumors, being an important source of IFN-γ. Natural killer dendritic cells (NKDCs) were recently identified as a group of hybrid cells; some studies claim that they have lytic activity, produce IFN-γ and can also stimulate antigen-specific T cells. Interleukin 21 (IL-21) regulates the proliferation capacity and cytotoxicity of NK and T cells. The main objective of this study was to investigate if IL-21 influences the frequency of NKDCs in vitro as well as IFN-γ production and also to verify if these cells could enhance the antitumor activity against B16F10 tumor model in vivo. Splenocytes from C57BL/6 mice were isolated and the DC were enriched by immunomagnetic beads and cultured for four days with recombinant IL-21 (10, 20, 40 or 100 ng/ml). NKDC population was characterized as CD11clow/medB220+NK1.1+. Expanded cells were used to treat B16F10 tumor bearing mice and tumor growth was compared between the doses of IL-21 10 ng/ml and 20 ng/ml. The results indicate that IL-21 increases the expansion of splenic NKDCs in vitro in doses of 10 ng/ml and 20 ng/ml and these cells produce IFN-γ. In vivo, cells expanded with IL-21 and injected directly into the growing tumor efficiently reduced the tumor size. Together, these results showed for the first time that IL-21 influences the biology and the effector activity of NKDCs.

Interannual variability of phytoplankton in the main rivers of the Upper Paraná River floodplain, Brazil: influence of upstream reservoirs / Variabilidade Interanual do Fitoplâncton dos principais rios da planície de inundação do Alto Rio Paraná, Brasil: influência de reservatórios a montante

The interannual variation of phytoplankton communities in the three main rivers of the Upper Paraná River floodplain is evaluated in relation to changes in the hydrosedimentological regime. These changes are a result of climatic variability and the formation of Porto Primavera Reservoir, located at the upper Paraná River. Phytoplankton species richness and density were investigated in rivers during a prior period (1993-1994) and eight years after reservoir impoundment (2000-2007). Multiple analyses were conducted to test the differences between these time periods in order to find predictor variables for phytoplankton attributes. A total of 454 phytoplanktonic taxa were found. The regression analysis revealed significant differences between periods. In the years following construction of the Porto Primavera dam, species richness was lower in the Paraná River and density was higher in the three rivers. In general, the algal density decreased from 2005 to 2007. Diatoms and cyanobacteria contributed significantly to the total density during the period from March 1993 to February 1994. The years 2000-2007 presented the lowest diatom contribution to species richness and the highest cyanobacteria contribution. From 2000 on, cryptomonads and cyanobacteria dominated. The interannual variability of phytoplankton was probably influenced by changes in hydrosedimentological regime due to climatic variations (La Niña and El Niño - Southern Oscillation events - ENSO) and the operational procedures associated with an upstream reservoirs. Studies on climatic variability and its effects on hydrosedimentological regimes of the Paraná, Baía and Ivinhema rivers and the biota therein are necessary to obtain subsidies for management, including decisions related to the operation of dams upstream and downstream of the study area, with the purpose of minimizing risks to the Environmental Protection Area.

A variação interanual da estrutura fitoplanctônica nos três principais rios da planície de inundação do Alto Rio Paraná foi avaliada em relação às modificações no regime hidrossedimentológico. Essas modificações são resultantes da variabilidade climática e da formação do reservatório de Porto Primavera, localizado no Alto Rio Paraná. Foi avaliada a riqueza de espécies e a densidade, em um período anterior à construção da UHE de Porto Primavera (1993-1994) e nos 8 anos seguintes (2000-2007) a formação do reservatório. Foram realizadas análises de regressão múltipla para testar as diferenças entre os períodos e buscar variáveis preditoras dos atributos fitoplanctônicos analisados. Foram registrados 454 táxons. A análise de regressão evidenciou variações significativas entre os períodos analisados. A riqueza de espécies foi menor no Rio Paraná e a densidade fitoplanctônica foi maior nos três rios nos anos seguintes à formação do reservatório de Porto Primavera. Registrou-se um decréscimo nos valores de densidade nos anos de 2005 a 2007. Diatomáceas e cianobactérias contribuíram significativamente para a densidade durante o período de março de 1993 a fevereiro de 1994. No período de 2000 a 2007 ocorreu menor contribuição de diatomáceas e, maior contribuição de cianobactérias para a riqueza de espécies. A partir de 2000, criptofíceas e cianobactérias dominaram. As alterações nos atributos analisados também estiveram associadas às flutuações no regime hidrossedimentológico dos rios estudados, provavelmente, influenciadas pelas fases La Niña e El Niño (Oscilação Sul - ENOS). Estes resultados salientam a necessidade de estudos enfocando a variabilidade climática e seus efeitos sobre o regime hidrossedimentológico do Rio Paraná e, sobre sua biota, de modo a fornecer subsídios para o manejo adequado, incluindo decisões quanto à operação das barragens situadas a montante e jusante da região de estudo, para minimizar as perdas de biodiversidade nesta ...

Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20 percent, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20 percent. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

Antibiotic use and the development of Crohn's disease.

BACKGROUND: Few environmental determinants of Crohn's disease are well established. Some observational data exist to implicate antibiotic use as a risk factor but these are derived from studies using questionnaires to assess reported antibiotic use that were susceptible to recall bias. We have therefore explored this relationship in prospectively gathered data. METHODS: We selected incident cases of Crohn's disease from the General Practice Research Database with at least five years of data prior to diagnosis. Controls with five years of complete data were randomly selected. Data were extracted on smoking, drug prescriptions, age, sex, and a variety of symptoms and diagnoses that might be indicative of occult Crohn's disease. Logistic regression was used to investigate the relationship between antibiotic use and Crohn's disease. RESULTS: A total of 587 Crohn's disease cases and 1460 controls were available for analysis. We found that antibiotic use 2-5 years pre-diagnosis occurred in 71% of cases compared with 58% of controls (p<0.001), and the median number of courses was two in the cases and one in the controls (p<0.001). Adjusting for age, sex, smoking, and use of other drugs, antibiotic use had an odds ratio of 1.32 (1.05-1.65). We were unable to show specificity to any subgroup of antibacterials. Associations similar to that with antibiotics were also found with oral contraceptive, cardiovascular, and neurological drugs. CONCLUSIONS: We found a statistically significant association between Crohn's disease and prior antibiotic use. This cannot be explained by recall bias, but due to lack of specificity it is unclear whether it is causal.

Feasibility of testing for Chlamydia trachomatis in a general population sexual behaviour survey in Slovenia.

Our objective was to assess the feasibility of integrating first void urine (FVU) specimens testing for Chlamydia trachomatis genitourinary infection into a general population sexual behaviour survey. A total of 752 randomly selected respondents aged 18 to 54 were enrolled into the survey. Face to face interviewing with self-administered sensitive questions was used. Overall survey response rate was 77.4%. A convenience sub-sample of 83 respondents were invited to provide FVU specimens for confidential testing for C. trachomatis genitourinary infection. Fifty-five complied. This resulted in 66% FVU specimen participation rate among targeted respondents. Two specimens tested positive by Amplicor polymerase chain reaction. High feasibility study overall response rate indicated good acceptability of the survey. It proved feasible to collect FVU specimens for C. trachomatis testing in the small sub-sample. Consequently, we proceeded with integration of testing for C. trachomatis into the ongoing main survey.

Upward trend in the rate of detection of new cases of leprosy in the State of Bahia, Brazil.

BACKGROUND: The worldwide fall in the rate of detection of new cases of leprosy has been partly attributed to the introduction of multidrug therapy and other improvements in control programs. However, the rate of detection of new cases has not decreased in Brazil. METHODS: An analysis was made of the temporal distribution of 18,872 newly reported leprosy cases in Bahia, Brazil, from 1974 to 1997. Population denominators for the annual detection rate were obtained from population estimates based on the national census. Trends were presented by sex, date of birth, date of diagnosis, date of release, clinical form and by residence in areas which had notified cases in the 5 years prior to the rise in detection rate. RESULTS: There was a marked increase in the new case detection rate (NCDR) in the State of Bahia, from 0.19 to 1.43 cases per 10,000 inhabitants during the study period, an increment of nearly 7% to 8% per year. This increase was also observed in people aged 14 years and younger. During this period tuberculoid and indeterminate forms have become predominant among women and younger people. The average age of male cases has shifted toward younger ages. CONCLUSIONS: We interpret this pattern to mean that the increase in NCDR reflects a real increase in incidence of leprosy, whether or not accompanied by improved detection.

Investigation of under-ascertainment in epidemiological studies based in general practice.

BACKGROUND: One of the aims of the Study of Infectious Intestinal Disease (IID) in England is to estimate the incidence of IID presenting to general practice. This sub-study aims to estimate and correct the degree of under-ascertainment in the national study. METHODS: Cases of presumed IID which presented to general practice in the national study had been ascertained by their GP. In 26 general practices, cases with computerized diagnoses suggestive of IID were identified retrospectively. Cases which fulfilled the case definition of IID and should have been ascertained to the coordinating centre but were not, represented the under-ascertainment. Logistic regression modelling was used to identify independent factors which influenced under-ascertainment. RESULTS: The records of 2021 patients were examined, 1514 were eligible and should have been ascertained but only 974 (64%) were. There was variation in ascertainment between the practices (30% to 93%). Patient-related factors independently associated with ascertainment were: i) vomiting only as opposed to diarrhoea with and without vomiting (OR 0.37) and ii) consultation in the surgery as opposed to at home (OR 2.18). Practice-related factors independently associated with ascertainment were: i) participation in the enumeration study component (OR 1.78), ii) a larger number of partners (OR 0.3 for 7-8 partners); iii) rural location (OR 2.27) and iv) previous research experience (OR 1.92). Predicted ascertainment percentages were calculated according to practice characteristics. CONCLUSION: Under-ascertainment of IID was substantial (36%) and non-random and had to be corrected. Practice characteristics influencing variation in ascertainment were identified and a multivariate model developed to identify adjustment factors which could be applied to individual practices. Researchers need to be aware of factors which influence ascertainment in acute epidemiological studies based in general practice.

The influence of maternal nutritional factors on intrauterine growth retardation in Brazil.

A case-control study of 712 Brazilian mother-baby pairs was performed to assess maternal nutritional factors, more specifically low or marginal concentrations of vitamin A, folate and iron, as risk factors for intrauterine growth retardation (IUGR). Newborns were classified as being IUGR according to the Lubchenco classification. The gestational age of the newborns was evaluated by the Capurro method. Vitamin A, folate, ferritin and haemoglobin were measured by high-performance liquid chromatography, radioimmunoassay, immunoenzymetric assay and by the cyanmethaemoglobin method respectively. The relationship between maternal nutritional status and IUGR was investigated using stratification and logistic regression. According to the final logistic regression model, the risk factors for IUGR were: maternal body weight, per capita income, cigarette smoking, maternal weight gain, prior history of low birthweight, high maternal ferritin, beer intake and coffee intake. Specific interventions likely to have the major short-term impact in this region are not directly related to nutritional factors, but to efforts to reduce or eliminate toxic exposures. Over the long term, improvement in maternal nutritional status and socioeconomic conditions would be expected to produce important benefits.

Coffee consumption and intrauterine growth retardation in Brazil.

OBJECTIVE: To examine the association between coffee consumption in pregnancy and foetal growth. DESIGN: Retrospective unmatched case-control study. SETTING: Maternidade de Campinas, Universidade Estadual de Campinas, Pontificia Universidade Católica de Campinas, Hospital Albert Sabin. SUBJECTS: 356 mother/baby pairs who had interauterine growth retardation (IUGR) and 356 mother/baby pairs who were appropriate for gestational age (AGA). INTERVENTIONS: Newborns were classified as being IUGR according to the Lubchenco classification. Gestational age of the newborns was evaluated by the Capurro method. Coffee consumption in pregnancy was assessed by a food frequency questionnaire. Coffee consumption and a range of risk factors for IUGR were stratified and entered into a logistic regression model. The final results were expressed by the attributable risk percent (AR%). RESULTS: More IUGR mothers (85.4%) than AGA mothers (70.5%) ingested coffee in pregnancy (OR = 2.45; P < 0.001). The proportion of mothers who delivered IUGR babies increased as the average consumption of coffee increased (test for trend = 31.76; P < 0.001). The tendency for heavy coffee drinkers to deliver IUGR babies remained after controlling for alcohol intake and cigarette smoking (P < 0.001). According to the logistic regression model and to the attributable risk percent (AR% = 28.0%), coffee consumption, (independent of average coffee consumption) was an important preventable cause of IUGR in this Brazilian population. CONCLUSIONS: We recommend moderation in the consumption of coffee in pregnancy, since intrauterine growth retardation increases the risk of perinatal and neonatal morbidity and mortality. Further large prospective studies evaluating the content of caffeine in the coffee consumed by this population is advised.

Vitamin A, folate, and iron concentrations in cord and maternal blood of intra-uterine growth retarded and appropriate birth weight babies.

OBJECTIVES: (i) To evaluate the relationship between the levels of vitamin A, folate and iron in maternal blood and cord blood from mother-baby pairs who had intra-uterine growth retardation (IUGR) and appropriate birth weight (ABW) for gestational age. (ii) To assess low or marginal levels of vitamin A, folate and iron as risk factors for IUGR. DESIGN: Retrospective unmatched case-control study. SETTING: Maternidade de Campinas, Universidade Estadual de Campinas, Pontificia Universidade Catolica de Campinas, Hospital Albert Sabin. SUBJECTS: 356 mother-baby pairs who had IUGR and 356 mother-baby pairs who had ABW for gestational age. INTERVENTIONS: Newborns were classified as being IUGR according to the Lubchenco classification. Gestational age of the newborns was evaluated by the Capurro method. Vitamin A, folate, ferritin, and haemoglobin were measured respectively by high performance liquid chromatography (HPLC), radioimmunoassay, immunoenzymetric assay and by the cyanmethaemoglobin method. RESULTS: The percentages of IUGR babies with abnormal levels of nutritional indices compared with ABW babies were 33.1 vs 14.6 for vitamin A, 25.7 vs 19.9 for red blood cell (RBC) folate, 37.0 vs 21.4 for haemoglobin, but similar for ferritin. The percentages of IUGR mothers with abnormal levels of nutritional indices compared to ABW mothers were similar (1.1 vs 1.4) for vitamin A, and 36.8 vs 32.1 for RBC folate. IUGR mothers were less often anaemic (43.2 vs 50.8), but tended to have higher levels of ferritin (37.6 vs 23.9) compared to ABW mothers. CONCLUSIONS: These results indicate marked differences in cord blood between IUGR and ABW with small differences in maternal levels. They suggest that micronutrient deficiency is the result of being born small rather than vice versa. The high levels of ferritin in IUGR mothers may reflect subclinical maternal infection contributing to IUGR. Maternal micronutrient deficiency is unlikely to be a causative factor for IUGR in this population. SPONSORSHIP: ODA (Overseas Development Agency), United Kingdom; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico), Brazil.