First Description of a Cluster of Acute/Subacute Paracoccidioidomycosis Cases and Its Association with a Climatic Anomaly

Background: Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis. Methodology/Principal Findings: A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in Sao Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 (similar to 2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal (similar to 1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Nino event, the strongest in the last 50 years. Conclusions/Significance: We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Nino Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures.

Development of Hepatitis C Virus Genotyping by Real-Time PCR Based on the NS5B Region

Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response to antiviral therapy. The aim of this study was to develop and evaluate a novel real-time PCR method for HCV genotyping based on the NS5B region. Methodology/Principal Findings: Two triplex reaction sets were designed, one to detect genotypes 1a, 1b and 3a; and another to detect genotypes 2a, 2b, and 2c. This approach had an overall sensitivity of 97.0%, detecting 295 of the 304 tested samples. All samples genotyped by real-time PCR had the same type that was assigned using LiPA version 1 (Line in Probe Assay). Although LiPA v. 1 was not able to subtype 68 of the 295 samples (23.0%) and rendered different subtype results from those assigned by real-time PCR for 12/295 samples (4.0%), NS5B sequencing and real-time PCR results agreed in all 146 tested cases. Analytical sensitivity of the real-time PCR assay was determined by end-point dilution of the 5000 IU/ml member of the OptiQuant HCV RNA panel. The lower limit of detection was estimated to be 125 IU/ml for genotype 3a, 250 IU/ml for genotypes 1b and 2b, and 500 IU/ml for genotype 1a. Conclusions/Significance: The total time required for performing this assay was two hours, compared to four hours required for LiPA v. 1 after PCR-amplification. Furthermore, the estimated reaction cost was nine times lower than that of available commercial methods in Brazil. Thus, we have developed an efficient, feasible, and affordable method for HCV genotype identification.

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

Background: Ser-249 TP53 mutation (249(Ser)) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249Ser mutation in HCC from patients in Brazil. Methods: We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249Ser mutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR. Results: 249Ser mutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249Ser mutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249Ser mutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249Ser mutation (OR = 2.415, 95% CI = 1.001 - 5.824, p = 0.05). The mean size of 249Ser HCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249Ser mutation. Conclusion: Our results indicate that 249Ser mutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.

Real-Time PCR in HIV/Trypanosoma cruzi Coinfection with and without Chagas Disease Reactivation: Association with HIV Viral Load and CD4(+) Level

Background: Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology: Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings: qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4(+) cells or the CD4(+)/CD8(+) ratio. Conclusions: qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4(+) cells/mm(3) and the CD4(+)/CD8(+) ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy.

Time variation of some selected topics in bioethical publications

Objective: To analyse the time variation of topics in bioethical publications as a proxy of the relative importance. Methods: We searched the Medline database for bioethics publications using the words ""ethics or bioethics'', and for 360 specific topics publications, associating Medical Subject Heading topic descriptors to those words. We calculated the ratio of bioethics publications to the total publications of Medline, and the ratio of each topic publications to the total bioethics publications, for five-year intervals, from 1970 to 2004. We calculated the time variation of ratios, dividing the difference between the highest and lowest ratio of each topic by its highest ratio. Four topics were described, selected to illustrate different patterns of variation: ""Induced Abortion'', ""Conflict of Interest'', ""Acquired Immunodeficiency Syndrome'', ""Medical Education.'' Results: The ratio of bioethics publications to total Medline publications increased from 0.003 to 0.012. The variation of the topic's ratios was higher than 0.7 for 68% of the topics. The Induced Abortion ratios decreased from 0.12 to 0.02. Conflict of Interest ratios increased from zero to 0.07. The Acquired Immunodeficiency Syndrome ratios were nearly zero in the first three intervals, had a peak of 0.06 during 1985-9, followed by a decrease to 0.01. Medical Education ratios varied few, from 0.04 to 0.03. Conclusions: There was an increase of bioethical publications in the Medline database. The topics in bioethics literature have an important time variation. Some factors were suggested to explain this variation: current legal cases, resolution of the issue, saturation of a discussion and epidemiologic importance.

The International Collaboration on Air Pollution and Pregnancy Outcomes: Initial Results

BACKGROUND: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design. OBJECTIVES: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach. METHODS: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter <= 10 mu m in aerodynamic diameter (PM(10)) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables. RESULTS: Among locations with data for the PM(10) analysis, ORs estimating the relative risk of term LBW associated with a 10-mu g/m(3) increase in average PM(10) concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30-1.35] for the Netherlands to 1.15 (95% CI, 0.61-2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations. CONCLUSIONS: Variability in PM(10)-LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.

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.

Impact of outdoor biomass air pollution on hypertension hospital admissions

Background This study aimed to evaluate the association between the total suspended particles (TSP) generated from burning sugar cane plantations and the incidence of hospital admissions from hypertension in the city of Araraquara. Methods The study was an ecological time-series study. Total daily records of hypertension (ICD 10th I10-15) were obtained from admitted patients of all ages in a hospital in Araraquara, Sao Paulo State, Brazil, from 23 March 2003 to 27 July 2004. The daily concentration of TSP (mu g/m(3)) was obtained using a Handi-Vol sampler placed in downtown Araraquara. The local airport provided daily measures of temperature and humidity. In generalised linear Poisson regression models, the daily number of hospital admissions for hypertension was considered to be the dependent variable and the daily TSP concentration the independent variable. Results TSP presented a lagged effect on hypertension admissions, which was first observed 1 day after a TSP increase and remained almost unchanged for the following 2 days. A 10 mu g/m(3) increase in the TSP 3 day moving average lagged in 1 day led to an increase in hypertension-related hospital admissions during the harvest period (12.5%, 95% CI 5.6% to 19.9%) that was almost 30% higher than during non-harvest periods (9.0%, 95% CI 4.0% to 14.3%). Conclusions Increases in TSP concentrations were associated with hypertension-related hospital admissions. Despite the benefits of reduced air pollution in urban cities achieved by using ethanol produced from sugar cane to power automobiles, areas where the sugar cane is produced and harvested were found to have increased public health risk.

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.

Cardiac arrhythmia emergency room visits and environmental air pollution in Sao Paulo, Brazil

Objectives: Air-pollution exposure has been associated with increased cardiovascular hospital admissions and mortality in time-series studies. We evaluated the relation between air pollutants and emergency room (ER) visits because of cardiac arrhythmia in a cardiology hospital. Methods: In a time-series study, we evaluated the association between the emergency room visits as a result of cardiac arrhythmia and daily variations in SO2, CO, NO2, O-3 and PM10, from January 1998 to August 1999. The cases of arrhythmia were modelled using generalised linear Poisson regression models, controlling for seasonality (short-term and long-term trend), and weather. Results: Interquartile range increases in CO (1.5 ppm), NO2 (49,5 mu g/m(3)) and PM10 (22.2 mu g/m(3)) on the concurrent day were associated with increases of 12.3% (95% CI: 7.6% to 17.2%), 10.4% (95% CI: 5.2% to 15.9%) and 6.7% (95% CI: 1.2% to 12.4%) in arrhythmia ER visits, respectively. PM10, CO and NO2 effects were dose-dependent and gaseous pollutants had thresholds. Only CO effect resisted estimates in models with more than one pollutant. Conclusions: Our results showed that air pollutant effects on arrhythmia are predominantly acute starting at concentrations below air quality standards, and the association with CO and NO2 suggests a relevant role for pollution caused by cars.

Detection of dengue virus in saliva and urine by real time RT-PCR

Early diagnosis of dengue virus (DENV) infection is important for patient management and control of dengue outbreaks. The objective of this study was to analyze the usefulness of urine and saliva samples for early diagnosis of DENV infection by real time RT-PCR. Two febrile patients, who have been attended at the General Hospital of the School of Medicine of Ribeirao Preto, Sao Paulo University were included in the study. Serum, urine and saliva samples collected from both patients were subjected to real time RT-PCR for DENV detection and quantification. Dengue RNA was detected in serum, urine and saliva samples of both patients. Patient 1 was infected with DENV-2 and patient 2 with DENV-3. Data presented in this study suggest that urine and saliva could be used as alternative samples for early diagnosis of dengue virus infection when blood samples are difficult to obtain, e.g.,in newborns and patients with hemorrhagic syndromes.

Viral mutation and its influence in the time evolution of the immunizations

In this paper, we study the behavior of immune memory against antigenic mutation. Using a dynamic model proposed by one of the authors in a previous study (A. de Castro [Phys. J. Appl. Phys. 33, 147 (2006) and Simul. Mod. Pract. Theory. 15, 831 (2007)]), we have performed simulations of several inoculations, where in each virtual sample the viral population undergoes mutations. Our results suggest that the sustainability of the immunizations is dependent on viral variability and that the memory lifetimes are not random, what contradicts what was suggested by Tarlinton et al. [Curr. Opin. Immunol. 20, 162 (2008)]. We show that what may cause an apparent random behavior of the immune memory is the antigenic variability.

Influence of pulse repetition rate on temperature rise and working time during composite filling removal with the Er : YAG laser

Objective: The purpose of this study was to assess the efficacy of Er:YAG laser energy for composite resin removal and the influence of pulse repetition rate on the thermal alterations occurring during laser ablation. Materials and Methods: Composite resin filling was placed in cavities (1.0 mm deep) prepared in bovine teeth and the specimens were randomly assigned to five groups according to the technique used for composite filling removal. In group I (controls), the restorations were removed using a high-speed diamond bur. In the other groups, the composite fillings were removed using an Er: YAG laser with different pulse repetition rates: group 2-2 Hz; group 3-4 Hz; group 4-6 Hz; and group 5-10 Hz. The time required for complete removal of the restorative material and the temperature changes were recorded. Results: Temperature rise during composite resin removal with the Er: YAG laser occurred in the substrate underneath the restoration and was directly proportional to the increase in pulse repetition rate. None of the groups had a temperature increase during composite filling removal of more than 5.6 degrees C, which is considered the critical point above which irreversible thermal damage to the pulp may result. Regarding the time for composite filling removal, all the laser-ablated groups (except for group 5 [10 Hz]) required more time than the control group for complete elimination of the material from the cavity walls. Conclusion: Under the tested conditions, Er: YAG laser irradiation was efficient for composite resin ablation and did not cause a temperature increase above the limit considered safe for the pulp. Among the tested pulse repetition rates, 6 Hz produced minimal temperature change compared to the control group (high-speed bur), and allowed composite filling removal within a time period that is acceptable for clinical conditions.

Elevated Risk for HIV-1 Infection in Adolescents and Young Adults in Sao Paulo, Brazil

Background. Recent studies have sought to describe HIV infection and transmission characteristics around the world. Identification of early HIV-1 infection is essential to proper surveillance and description of regional transmission trends. In this study we compare people recently infected (RI) with HIV-1, as defined by Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS), to those with chronic infection. Methodology/Principal Findings. Subjects were identified from 2002-2004 at four testing sites in Sao Paulo. Of 485 HIV-1-positive subjects, 57 (12%) were defined as RI. Of the participants, 165 (34.0%) were aware of their serostatus at the time of HIV-1 testing. This proportion was statistically larger (p<0.001) among the individuals without recent infection (n = 158, 95.8%) compared to 7 individuals (4.2%) with recently acquired HIV-1 infection. In the univariate analysis, RI was more frequent in,25 and >59 years-old age strata (p < 0.001). The majority of study participants were male (78.4%), 25 to 45 years-old (65.8%), white (63.2%), single (61.7%), with family income of four or more times the minimum wage (41.0%), but with an equally distributed educational level. Of those individuals infected with HIV-1, the predominant route of infection was sexual contact (89.4%), with both hetero (47.5%) and homosexual (34.5%) exposure. Regarding sexual activity in these individuals, 43.9% reported possible HIV-1 exposure through a seropositive partner, and 49.4% reported multiple partners, with 47% having 2 to 10 partners and 37.4% 11 or more; 53.4% of infected individuals reported condom use sometimes; 34.2% reported non-injecting, recreational drug use and 23.6% were reactive for syphilis by VDRL. Subjects younger than 25 years of age were most vulnerable according to the multivariate analysis. Conclusions/Significance. In this study, we evaluated RI individuals and discovered that HIV-1 has been spreading among younger individuals in Sao Paulo and preventive approaches should, therefore, target this age stratum.