Selectivity in reduction of natural furanoheliangolides with Stryker's reagent

Reduction of the natural sesquiterpene lactones furanoheliangolides with Stryker's reagent is an effective process for producing eremantholides through a biomimetic pathway. Other reduction products are also formed. Oxygenated functions at C-15 of the furanoheliangolide produce an increase in the velocities of the reactions and reduce the chemoselectivity of the reagent.

Selenium and Mercury in the Brazilian Amazon: Opposing Influences on Age-Related Cataracts

BACKGROUND: Age-related cataracts (ARCs) are an important cause of blindness in developing countries. Although antioxidants may be part of the body's defense to prevent ARC, environmental contaminants may contribute to cataractogenesis. In fish-eating populations of the lower Tapajos region, elevated exposure to mercury (Hg) has been reported, and blood levels of selenium (Se) range from normal to very high (> 1,000 mu g/L). OBJECTIVES: We examined ARCs in relation to these elements among adults (>= 40 years of age) from 12 riverside communities. METHODS: Participants (n = 211) provided blood samples and underwent an extensive ocular examination. Inductively coupled plasma mass spectrometry was used to assess Hg and Se in blood and plasma. RESULTS: One-third (n = 69; 32.7%) of the participants had ARC. Lower plasma Se (P-Se; < 25th percentile, 110 mu g/L) and higher blood Hg (B-Hg; >= 25th percentile, 25 mu g/L) were associated with a higher prevalence odds ratio (POR) of ARC [adjusted POR (95% confidence interval), 2.69 (1.11-6.56) and 4.45 (1.43-13.83), respectively]. Among participants with high P-Se, we observed a positive but nonsignificant association with high B-Hg exposure, whereas among those with low B-Hg, we observed no association for P-Se. However, compared with the optimum situation (high P-Se, low B-Hg), the POR for those with low P-Se and high B-Hg was 16.4 (3.0-87.9). This finding suggests a synergistic effect. CONCLUSION: Our results suggest that persons in this population with elevated Hg, the cataractogenic effects of Hg may be offset by Se. Because of the relatively small sample size and possible confounding by other dietary nutrients, additional studies with sufficient power to assess multiple nutrient and toxic interactions are required to confirm these findings.

Subclinical hyperthyroidism and dementia: the Sao Paulo Ageing & Health Study (SPAH)

Background: Several epidemiologic studies have shown a possible association between thyroid function and cognitive decline. Our aim was to evaluate the association of subclinical hyperthyroidism and dementia in a population sample of older people Methods: A cross-sectional study - Sao Paulo Ageing & Health Study (SPAH) - in a population sample of low-income elderly people >= 65 years-old to evaluate presence of subclinical thyroid disease as a risk factor for dementia. Thyroid function was assessed using thyrotropic hormone and free-thyroxine as well as routine use of thyroid hormones or antithyroid medications. Cases of dementia were assessed using a harmonized one-phase dementia diagnostic procedure by the ""10/66 Dementia Research Group"" including Alzheimer's disease and vascular dementia. Logistic regression models were used to test a possible association between subclinical hyperthyroidism and dementia. Results and discussion: Prevalence of dementia and of subclinical hyperthyroidism were respectively of 4.4% and 3.0%. After age adjustment, we found an association of subclinical hyperthyroidism and any type of dementia and vascular dementia (Odds Ratio, 4.1, 95% Confidence Interval [95% CI] 1.3-13.1, and 5.3 95% CI, 1.1-26.4; respectively). Analyzing data by gender, we found an association of subclinical hyperthyroidism with dementia and Alzheimer's disease only for men (OR, 8.0; 95% CI, 1.5-43.4; OR, 12.4; 95% CI, 1.2-128.4; respectively). No women with subclinical hypothyroidism presented Alzheimer's disease in the sample. Conclusion: The results suggest a consistent association among people with subclinical hyperthyroidism and dementia.

Oral Health Promotion Through an Online Training Program for Medical Students

The objective of this study was to compare the impact on knowledge and counseling skills of face-to-face and Internet-based oral health training programs on medical students. Participants consisted of 148 (82 percent) of the 180 invited students attending their fifth academic year at the Faculty of Medicine, University of Sao Paulo, Brasil, in 2007. The interventions took place during a three-month training period in the clinical Center for Health Promotion, which comprised part of a clerkship in Internal Medicine. The students were divided into four groups: 1) Control Group (Control), with basic intervention; 2) Brochure Group (Br), with basic intervention plus complete brochure with oral health themes; 3) Cybertutor Group (Cy), with basic intervention plus access to an Internet-based training program about oral health themes; and 4) Cybertutor + Contact Group (Cy+C), the same as Cy plus brief proactive contact with a tutor. The impact of these interventions on student knowledge was measured with pre- and post assessments, and student skills in asking and counseling about oral health were assessed with an objective structured clinical examination (OSCE). Multivariate logistic regression models were applied to identify the odds ratios of scoring above Control's medians on the final assessment and the OSCE. In the results, Cy+C performed significantly better than Control on both the final assessment (OR 9.4; 95% CI 2.7-32.8) and the OSCE (OR 5.6; 95% CI 1.9-16.3) and outperformed all the other groups. The Cy+C group showed the most significant increase in knowledge and the best skills in asking and counseling about oral health.

The family health system: analysis of a health survey in Sao Paulo, Brazil

Background The Family Health Strategy (FHS) has been implemented as a strategy for primary care improvement in Brazil. Working with teams that include one doctor, one nurse, auxiliary nurses and community health workers in predefined areas, the FHS began in 1994 (known then as the Family Health Program) and has since grown considerably. The programme has only recently undergone assessment of outcomes, in contrast to more routine evaluations of infrastructure and process. Methods In 2001, a health survey was carried out in two administrative districts (with 190 000 inhabitants) on the outskirts of the city of Sao Paulo, both partially served by the FHS. Chronic morbidity (hypertension, diabetes and ischaemic heart disease) of individuals aged 15 or older was studied in areas covered and not covered by the programme. Stratified univariate analysis was applied for sex, age, education, income, working status and social insurance of these populations. Multivariate analysis was applied where applicable. Results There was a distinct pattern in the morbidity profile of these populations, suggesting differentiated self-knowledge on chronic disease status in the areas served by the FHS. Conclusion The FHS can increase population awareness of chronic diseases, possibly through increasing access to primary care.

Urban air pollution and chronic obstructive pulmonary disease-related emergency department visits

Background: Patients with chronic obstructive pulmonary disease (COPD) can have recurrent disease exacerbations triggered by several factors, including air pollution. Visits to the emergency respiratory department can be a direct result of short-term exposure to air pollution. The aim of this study was to investigate the relationship between the daily number of COPD emergency department visits and the daily environmental air concentrations of PM(10), SO(2), NO(2), CO and O(3) in the City of Sao Paulo, Brazil. Methods: The sample data were collected between 2001 and 2003 and are categorised by gender and age. Generalised linear Poisson regression models were adopted to control for both short-and long-term seasonal changes as well as for temperature and relative humidity. The non-linear dependencies were controlled using a natural cubic spline function. Third-degree polynomial distributed lag models were adopted to estimate both lag structures and the cumulative effects of air pollutants. Results: PM(10) and SO(2) readings showed both acute and lagged effects on COPD emergency department visits. Interquartile range increases in their concentration (28.3 mg/m(3) and 7.8 mg/m(3), respectively) were associated with a cumulative 6-day increase of 19% and 16% in COPD admissions, respectively. An effect on women was observed at lag 0, and among the elderly the lag period was noted to be longer. Increases in CO concentration showed impacts in the female and elderly groups. NO(2) and O(3) presented mild effects on the elderly and in women, respectively. Conclusion: These results indicate that air pollution affects health in a gender-and age-specific manner and should be considered a relevant risk factor that exacerbates COPD in urban environments.

Cross-National Analysis of the Associations between Traumatic Events and Suicidal Behavior: Findings from the WHO World Mental Health Surveys

Background: Community and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues. Methodology/Principal Findings: Data on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries. Conclusions/Significance: This study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

Introduction: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Conclusions: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Cross-National Analysis of the Associations among Mental Disorders and Suicidal Behavior: Findings from the WHO World Mental Health Surveys

Background: Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts. Methods and Findings: Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9-8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5-5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies. Conclusions: This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts.

Psychometric properties of the Child Health Assessment Questionnaire (CHAQ) applied to children and adolescents with cerebral palsy

Background: Cerebral palsy (CP) patients have motor limitations that can affect functionality and abilities for activities of daily living (ADL). Health related quality of life and health status instruments validated to be applied to these patients do not directly approach the concepts of functionality or ADL. The Child Health Assessment Questionnaire (CHAQ) seems to be a good instrument to approach this dimension, but it was never used for CP patients. The purpose of the study was to verify the psychometric properties of CHAQ applied to children and adolescents with CP. Methods: Parents or guardians of children and adolescents with CP, aged 5 to 18 years, answered the CHAQ. A healthy group of 314 children and adolescents was recruited during the validation of the CHAQ Brazilian-version. Data quality, reliability and validity were studied. The motor function was evaluated by the Gross Motor Function Measure (GMFM). Results: Ninety-six parents/guardians answered the questionnaire. The age of the patients ranged from 5 to 17.9 years (average: 9.3). The rate of missing data was low(< 9.3%). The floor effect was observed in two domains, being higher only in the visual analogue scales (<= 35.5%). The ceiling effect was significant in all domains and particularly high in patients with quadriplegia (81.8 to 90.9%) and extrapyramidal (45.4 to 91.0%). The Cronbach alpha coefficient ranged from 0.85 to 0.95. The validity was appropriate: for the discriminant validity the correlation of the disability index with the visual analogue scales was not significant; for the convergent validity CHAQ disability index had a strong correlation with the GMFM (0.77); for the divergent validity there was no correlation between GMFM and the pain and overall evaluation scales; for the criterion validity GMFM as well as CHAQ detected differences in the scores among the clinical type of CP (p < 0.01); for the construct validity, the patients' disability index score (mean: 2.16; SD: 0.72) was higher than the healthy group ( mean: 0.12; SD: 0.23)(p < 0.01). Conclusion: CHAQ reliability and validity were adequate to this population. However, further studies are necessary to verify the influence of the ceiling effect on the responsiveness of the instrument.

Experimental Infection of the Opossum Didelphis aurita by Rickettsia felis, Rickettsia bellii, and Rickettsia parkeri and Evaluation of the Transmission of the Infection to Ticks Amblyomma cajennense and Amblyomma dubitatum

This work evaluated the infection of opossums (Didelphis aurita) by Rickettsia felis, Rickettsia bellii, and Rickettsia parkeri and their role as amplifier hosts for horizontal transmission to Amblyomma cajennense and/or Amblyomma dubitatum ticks. Infection in D. aurita was induced by intraperitoneal inoculation with R. felis (n = 4 opossums), R. bellii (n = 4), and R. parkeri (n = 2). Another group of six opossums were inoculated intraperitoneally with Leibovitz-15 sterile culture medium, representing the uninfected groups (n = 2 opossums simultaneously to each infected group). Opossum blood samples collected during the study were used for DNA extraction, followed by real-time polymerase chain reaction targeting the rickettsial gene gltA, hematology, and detection of Rickettsia spp.-reactive antibodies by indirect immunofluorescence assay. Opossums were infested with uninfected A. cajennense and/or A. dubitatum for 30 days postinoculation (DPI). Flat ticks molted from ticks fed on opossums were allowed to feed on uninfected rabbits, which were tested for seroconversion by immunofluorescence assay. Samples of flat ticks were also tested by real-time polymerase chain reaction. Inoculated opossums showed no clinical abnormalities. Antibodies to Rickettsia spp. were first detected at the second to fourth DPI, with detectable titers until the 150th DPI. Rickettsemia was detected only in one opossum inoculated with R. parkeri, at the eighth DPI. Only one A. cajennense tick (2.0%) previously fed on a R. parkeri-inoculated opossum became infected. None of the rabbits infested with opossum-derived ticks seroconverted. The study demonstrated that R. felis, R. bellii, and R. parkeri were capable to produce antibody response in opossums, however, with undetectable rickettsemia for R. felis and R. bellii, and very low rickettsemia for R. parkeri. Further studies must be done with different strains of these rickettsiae, most importantly the strains that have never gone through in vitro passages.

Incorporation of Real-Time PCR into Routine Public Health Surveillance of Culture Negative Bacterial Meningitis in Sao Paulo, Brazil

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%-100%) for N. meningitidis, 97.8% (85.5%-99.9%) for S. pneumoniae, and 66.7% (9.4%-99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil.

Trends in dermatomyositis- and polymyositis-related mortality in the state of Sao Paulo, Brazil, 1985-2007: multiple cause-of-death analysis

Background: Dermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of Sao Paulo, Brazil, between 1985 and 2007. Methods: We analyzed mortality data from the Sao Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant. Results: Over a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age-and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 +/- 20.81 years for DM and 54.24 +/- 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03). Conclusions: Our study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM.

Aqueous Extract of Brazilian Green Propolis: Primary Components, Evaluation of Inflammation and Wound Healing by Using Subcutaneous Implanted Sponges

Propolis is a chemically complex resinous bee product which has gained worldwide popularity as a means to improve health condition and prevent diseases. The main constituents of an aqueous extract of a sample of green propolis from Southeast Brazil were shown by high performance liquid chromatography/mass spectroscopy/mass spectroscopy to be mono- and di-O-caffeoylquinic acids; phenylpropanoids known as important constituents of alcohol extracts of green propolis, such as artepillin C and drupanin were also detected in low amounts in the aqueous extract. The anti-inflammatory activity of this extract was evaluated by determination of wound healing parameters. Female Swiss mice were implanted subcutaneously with polyesther-polyurethane sponge discs to induce wound healing responses, and administered orally with green propolis (500mg kg(-1)). At 4, 7 and 14 days post-implantation, the fibrovascular stroma and deposition of extracellular matrix were evaluated by histopathologic and morphometric analyses. In the propolis-treated group at Days 4 and 7 the inflammatory process in the sponge was reduced in comparison with control. A progressive increase in cell influx and collagen deposition was observed in control and propolis-treated groups during the whole period. However, these effects were attenuated in the propolis-treated group at Days 4 and 7, indicating that key factors of the wound healing process are modulated by propolis constituents.

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.