Validation of dot blot hybridization and denaturing high performance liquid chromatography as reliable methods for TP53 codon 72 genotyping in molecular epidemiologic studies

Background: Mutations in TP53 are common events during carcinogenesis. In addition to gene mutations, several reports have focused on TP53 polymorphisms as risk factors for malignant disease. Many studies have highlighted that the status of the TP53 codon 72 polymorphism could influence cancer susceptibility. However, the results have been inconsistent and various methodological features can contribute to departures from Hardy-Weinberg equilibrium, a condition that may influence the disease risk estimates. The most widely accepted method of detecting genotyping error is to confirm genotypes by sequencing and/or via a separate method. Results: We developed two new genotyping methods for TP53 codon 72 polymorphism detection: Denaturing High Performance Liquid Chromatography (DHPLC) and Dot Blot hybridization. These methods were compared with Restriction Fragment Length Polymorphism (RFLP) using two different restriction enzymes. We observed high agreement among all methodologies assayed. Dot-blot hybridization and DHPLC results were more highly concordant with each other than when either of these methods was compared with RFLP. Conclusions: Although variations may occur, our results indicate that DHPLC and Dot Blot hybridization can be used as reliable screening methods for TP53 codon 72 polymorphism detection, especially in molecular epidemiologic studies, where high throughput methodologies are required.

Mild myocardial infarction - A classification problem in epidemiologic studies

In studies assessing the trends in coronary events, such as the World Health Organization (WHO) MONICA Project (multinational MONItoring of trends and determinants of CArdiovascular disease), the main emphasis has been on coronary deaths and non-fatal definite myocardial infarctions (MI). It is, however, possible that the proportion of milder MIs may be increasing because of improvements in treatment and reductions in levels of risk factors. We used the MI register data of the WHO MONICA Project to investigate several definitions for mild non-fatal MIs that would be applicable in various settings and could be used to assess trends in milder coronary events. Of 38 populations participating in the WHO MONICA MI register study, more than half registered a sufficiently wide spectrum of events that it was possible to identify subsets of milder cases. The event rates and case fatality rates of MI are clearly dependent on the spectrum of non-fatal MIs, which are included. On clinical grounds we propose that the original MONICA category ''non-fatal possible MI'' could bt:divided into two groups: ''non fatal probable MI'' and ''prolonged chest pain.'' Non-fatal probable MIs are cases, which in addition to ''typical symptoms'' have electrocardiogram (EGG) or enzyme changes suggesting cardiac ischemia, but not severe enough to fulfil the criteria for non-fatal definite MI In more than half of the MONICA Collaborating Centers, the registration of MI covers these milder events reasonably well. Proportions of non-fatal probable MIs vary less between populations than do proportions of non fatal possible MIs. Also rates of non-fatal probable MI are somewhat more highly correlated with rates of fatal events and non-fatal definite MI. These findings support the validity of the category of non-fatal probable MI. In each center the increase in event rates and the decrease in case-fatality due to the inclusion of non-fatal probable MI was lar er for women than men. For the WHO MONICA Project and other epidemiological studies the proposed category of non-fatal probable MIs can be used for assessing trends in rates of milder MI. Copyright (C) 1997 Elsevier Science Inc.

Epidemiologic studies of chagas' disease in the urban zone of Teresina. State of Piauí, northeastern Brazil

The triatomine species Rhodnius nasutus and Triatoma pseudomaculata were captured on palm trees Orbignya martiana "babaçu ", in the urban zone of Teresina. This kind of palm tree is largely distributed in Piauí State. The predominant species was R. nasutus; the young in stars predominated. The infestation index of palm trees and the infection index of triatomines by flagellates were 96.0 ana 29.1%, respectively. Marsupiais, bats and a rodent were captured in palm trees. The flagellates found in both triatomines ana marsupiais were morphologically and biologically indistinguishable from Trypanosoma cruzi. Forty seven percent (481/1,025) of triatomines were found concentrated in six palm trees where marsupiais circulated. Of the total of 1,025 triatomines 230 (22%) were infected by flagellates and 53.0% (123/230) of these infected triatomines were present in the same six palm trees. No evidence of triatomine domiciliation or human transmission was observed in the houses in the vicinity of palm trees. The results suggest that marsupiais play an important role in the life-cycle of T. cruzi in this region. The natural focus of Chagas' disease, demonstrated in the present study could represent a potential epidemiological threat.

IgM-Immunofluorescence Test as a Diagnostic Tool for Epidemiologic Studies of Schistosomiasis in Low Endemic Areas

The high sensitivity and the ability to diagnose schistosomiasis in a very early phase after infection have indicated the detection of IgM antibodies to Schistosoma mansoni gut antigens by the immunofluorescence test (IgM-IFT) as a useful serological test for epidemiological studies in low endemic areas. When applied in a follow-up study for two years, higher rates of seroconversion from IFT negative to positive were observed during the summer months, suggesting seasonal transmission of schistosomiasis in the rural area of the municipality of Itariri (São Paulo, Brazil). In each survey, blood samples from about 600 schoolchildren were collected on filter paper and submitted to IgM-IFT. When the blood samples were classified for the IgM antibody levels, according to the intensity of fluorescent reaction observed at fluorescence microscopy, and correlated to the egg counts in the Kato-Katz positive patients, no association was observed. This observation might suggest that the intensity of fluorescence observed in the IgM-IFT, as an indicator of IgM antibody levels, could not be an useful seroepidemiological marker for classifying areas of low endemicity according to degrees of infection.

AN INVESTIGATION OF THE RELIABILITY AND VALIDITY OF THE CENTER FOR EPIDEMIOLOGIC STUDIES DEPRESSION SCALE IN THREE ETHNIC GROUPS

Epidemiologic studies of mental disorder have called attention to the need for identifying untreated cases and to the inadequacies of the instruments available for this purpose. Accurate case ascertainment devices are the basis of sound epidemiology. Without these, neither case classification nor analytic studies of risk factors is possible.^ The purpose of this research was to examine the reliability and validity of an instrument designed to measure depressive symptoms in community populations--the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Two particular foci of the study were whether or not the scale had the same statistical structure across three ethnic groups and whether or not the magnitude and pattern of rates of symptoms for these groups were affected by one source of response error, that due to response tendencies. The effects of age and education on the pattern and magnitude of rates also were examined. In addition, the reliability and validity of the measures of response tendencies were assessed.^ The study population consisted of residents of Alameda County, California. A stratified sample of approximately 700 whites, blacks and Mexican-Americans was interviewed in the summer and fall of 1978.^ The results of the analysis indicated that the scale was reliable and measured a similar content domain across the three ethnic groups. The unadjusted sex- and ethnic-specific rates of depressive symptoms showed an ethnic pattern for both sexes: rates for whites were lowest, those for Mexican-Americans were highest, and those for blacks were intermediate. Measures of response tendencies--need for social approval, trait desirability, and acquiescence--affected the magnitude of the rates for most comparisons. Likewise, the pattern of rates changed somewhat from that originally observed. The one fairly consistent observation was that rates for Mexican-American women were higher than those for the other two female subgroups in most of the comparisons. These results must be considered in the context of the reliability and validity assessment of the measures of response tendencies which indicated the tenuousness of these measures.^ Age affected the ethnic pattern of rates for men in an inconsistent way; for women, Mexican-Americans continued to have higher rates than whites or blacks in all age categories. Education affected the magnitude of rates for women but not for men. For both men and women, Mexican-Americans had higher rates in all educational strata. Rates for women showed an inverse association with education while those for men did not. ^

Protocol for epidemiologic studies of the health of Vietnam veterans /

Mode of access: Internet.

Epidemiologic studies for vaccine development

"PB 176 814."

Implications of non-response of older women to a short form of the Center for Epidemiologic Studies Depression Scale

The Center for Epidemiologic Studies Depression Scale (CES-D) is frequently used in epidemiological surveys to screen for depression, especially among older adults. This article addresses the problem of non-completion of a short form of the CES-D (CESD-10) in a mailed survey of 73- to 78-year-old women enrolled in the Australian Longitudinal Study on Women's Health. Completers of the CESD-10 had more education, found it easier to manage on available income and reported better physical and mental health. The Medical Outcomes Study Short Form Health Survey (SF-36) scores for non-completers were intermediate between those for women classified as depressed and not depressed using the CESD-10. Indicators of depression had an inverted U-shaped relationship with the number of missing CESD- 10 items and were most frequent for women with two to seven items missing. Future research should pay particular attention to the level of missing data in depression scales and report its potential impact on estimates of depression.

Validação da Versão Portuguesa da Center for Epidemiologic Studies Depression Scale for Children (CES-DC)

A Depressão na infância e adolescência, tal como na população adulta, é uma das perturbações mentais mais comuns. Uma vez que o seu aparecimento nestas faixas etárias conduz a graves consequências na idade adulta, é fundamental identificar os sintomas depressivos precocemente. Desta forma, os instrumentos de autorrelato têm um papel fundamental, uma vez que permitem com facilidade, de forma fidedigna e válida, ter acesso a formas de pensar, sentir e agir dos sujeitos. O objetivo do presente trabalho consistiu na tradução, adaptação e estudo da Center for Epidemiological Studies Depression Scale for Children (CES-DC) (Weissman, Orvash & Padian, 1980) para os adolescentes portugueses. A amostra é constituída por 417 adolescentes, com idades compreendidas entre os 12 e os 18 anos a frequentar o 3º ciclo do ensino básio e ensino secundário. Para o estudo da validade convergente e divergente da CES-DC, foram utilizados a Depression Anxiety Stress Scales (DASS 21) (Lovibond & Lovibond, 1995), o Children's Depresssion Inventory (CID) (Marujo, 1994) e a Students' Life Satisfaction Scale (SLSS) (Marques, Pais-Ribeiro & Lopez, 2007) que avaliam, respetivamente, os estados emocionais negativos (depressão, ansiedade e stress), a sintomatologia depressiva e a satisfação global com a vida. Os resultados obtidos mostram que a escala possui uma boa consistência interna, uma estabilidade temporal adequada, assim como uma boa validade. Sugerem, ainda, tratar-se de uma escala tridimensional: fator humor, fator interpessoal e fator felicidade. Estes dados permitem o avanço da Psicologia, no que diz respeito à avaliação e prática clínica com adolescentes. A utilidade do questionário deve ser verificada noutras faixas etárias, principalmente, nas de menos de 12 anos de idade, e também numa amostra clínica. Não obstante as limitações apontadas, os resultados sugerem que a CES-DC é um questionário útil na avaliação de sintomas depressivos nos adolescentes. / Depression in children and adolescents, as well as in adults, is one of the most common mental disorders. Since its appearance in these age groups leads to serious consequences in adulthood, it is critical to identify depressive symptoms in early stages. Therefore, self-report instruments play a key role in this contexto since they allow to easily, reliably and validly have access to ways the subject thinks, feels and acts. The aim of this study was to translate, adapt and study the Center for Epidemiological Studies Depression Scale for Children (CES-DC) (Weissman, Orvash & Padian, 1980) for portuguese adolescents. The sample consists of 417 adolescents, aged between 12 and 18 years old, attending the 3rd cycle of basic education and secondary education schools. To study the convergent and divergent validity of the CES-DC, the Depression Anxiety Stress Scales (DASS 21) (Lovibond & Lovibond, 1995) was used, along with the Children's depression Inventory (CDI) (Sailor, 1994) and the Students' Life Satisfaction Scale (SLSS) (Marques, Pais-Ribeiro & Lopez, 2007) that evaluate, respectively, the negative emotional states (depression, anxiety and stress), depressive symptoms and overall satisfaction with life. The results show that the evaluated scale presents a good internal consistency, an adequate temporal stability as well as good validity. They also suggest that this is a three-dimensional scale: humor factor, interpersonal factor and happiness factor. These data allow for the progress of psychology, regarding the assessment and clinical practice among adolescents. The usefulness of the questionnaire should be verified in other age groups, especially in children with less than 12 years old and in a clinical sample. Despite these limitations, the results suggest that CES-DC is useful in the assessment questionnaire of depressive symptoms in adolescents.

Clinic-epidemiologic study of human infection by Granada virus, a new phlebovirus within the sandfly fever Naples serocomplex.

Granada virus (GRV), a new phlebovirus within the Naples serocomplex, has been recently described in phlebotomine sandflies from Spain. The presence of anti-GRV immunoglobulin G (IgG) antibodies was investigated by indirect fluorescence assay (IFA) and neutralization test (NT) in 920 serum samples from the Granada population. By IFA, an overall GRV seroprevalence of 15.8% (N = 145) was observed, significantly increasing up to 65 years. NT was positive in 18% of anti-GRV IFA-positive samples. IgG antibodies against Toscana virus (TOSV), a hyperendemic phlebovirus within Granada province, were detected in 40% of anti-GRV-positive cases. Anti-GRV IgM antibodies were detected in 36 (6.6%) of 547 acute-phase serum samples from individuals with febrile illness, exanthema, and/or acute respiratory infection. All positives were anti-TOSV IgM-negative. GRV may infect humans, with most cases being asymptomatic. The codetection of anti-GRV and anti-TOSV IgG antibodies could be attributable to cross-reactivity or exposure to the same transmission vector.

Respiratory infection in congenital cardiac disease. Hospitalizations in young children in Spain during 2004 and 2005: the CIVIC Epidemiologic Study.

OBJECTIVES To evaluate the rate of hospitalization for acute respiratory tract infection in children less than 24 months with haemodynamically significant congenital cardiac disease, and to describe associated risk factors, preventive measures, aetiology, and clinical course. MATERIALS AND METHODS We followed 760 subjects from October 2004 through April 2005 in an epidemiological, multicentric, observational, follow-up, prospective study involving 53 Spanish hospitals. RESULTS Of our cohort, 79 patients (10.4%, 95% CI: 8.2%-12.6%) required a total of 105 admissions to hospital related to respiratory infections. The incidence rate was 21.4 new admissions per 1000 patients-months. Significant associated risk factors for hospitalization included, with odds ratios and 95% confidence intervals shown in parentheses: 22q11 deletion (8.2, 2.5-26.3), weight below the 10th centile (5.2, 1.6-17.4), previous respiratory disease (4.5, 2.3-8.6), incomplete immunoprophylaxis against respiratory syncytial virus (2.2, 1.2-3.9), trisomy 21 (2.1, 1.1-4.2), cardiopulmonary bypass (2.0, 1.1-3.4), and siblings aged less than 11 years old (1.7, 1.1-2.9). Bronchiolitis (51.4%), upper respiratory tract infections (25.7%), and pneumonia (20%) were the main diagnoses. An infectious agent was found in 37 cases (35.2%): respiratory syncytial virus in 25, Streptococcus pneumoniae in 5, and Haemophilus influenzae in 4. The odds ratio for hospitalization due to infection by the respiratory syncytial virus increases by 3.05 (95% CI: 2.14 to 4.35) in patients with incomplete prophylaxis. The median length of hospitalization was 7 days. In 18 patients (17.1%), the clinical course of respiratory infection was complicated and 2 died. CONCLUSIONS Hospital admissions for respiratory infection in young children with haemodynamically significant congenital cardiac disease are mainly associated with non-cardiac conditions, which may be genetic, malnutrition, or respiratory, and to cardiopulmonary bypass. Respiratory syncytial virus was the most commonly identified infectious agent. Incomplete immunoprophylaxis against the virus increased the risk of hospitalization.

Polymorphisms in DNA-Repair Genes in a Cohort of Prostate Cancer Patients from Different Areas in Spain: Heterogeneity between Populations as a Confounding Factor in Association Studies.

BACKGROUND Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics. OBJECTIVE To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias. DESIGN SETTING AND PARTICIPANTS A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer. RESULTS AND LIMITATIONS We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics. CONCLUSION Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.

A comparison of indices of glucose metabolism in five black populations: data from modeling the epidemiologic transition study (METS).

BACKGROUND: Globally, Africans and African Americans experience a disproportionate burden of type 2 diabetes, compared to other race and ethnic groups. The aim of the study was to examine the association of plasma glucose with indices of glucose metabolism in young adults of African origin from 5 different countries. METHODS: We identified participants from the Modeling the Epidemiologic Transition Study, an international study of weight change and cardiovascular disease (CVD) risk in five populations of African origin: USA (US), Jamaica, Ghana, South Africa, and Seychelles. For the current study, we included 667 participants (34.8 ± 6.3 years), with measures of plasma glucose, insulin, leptin, and adiponectin, as well as moderate and vigorous physical activity (MVPA, minutes/day [min/day]), daily sedentary time (min/day), anthropometrics, and body composition. RESULTS: Among the 282 men, body mass index (BMI) ranged from 22.1 to 29.6 kg/m(2) in men and from 25.8 to 34.8 kg/m(2) in 385 women. MVPA ranged from 26.2 to 47.1 min/day in men, and from 14.3 to 27.3 min/day in women and correlated with adiposity (BMI, waist size, and % body fat) only among US males after controlling for age. Plasma glucose ranged from 4.6 ± 0.8 mmol/L in the South African men to 5.8 mmol/L US men, while the overall prevalence for diabetes was very low, except in the US men and women (6.7 and 12 %, respectively). Using multivariate linear regression, glucose was associated with BMI, age, sex, smoking hypertension, daily sedentary time but not daily MVPA. CONCLUSION: Obesity, metabolic risk, and other potential determinants vary significantly between populations at differing stages of the epidemiologic transition, requiring tailored public health policies to address local population characteristics.