Genetic Polymorphisms of Matrix Metalloproteinases: Susceptibility and Prognostic Implications for Prostate Cancer

Purpose: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer. Materials and Methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by realtime polymerase chain reaction using TaqMan (R) fluorescent probes. Results: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042). Conclusions: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

Elevated Risk for HIV-1 Infection in Adolescents and Young Adults in São 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 São 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 São Paulo and preventive approaches should, therefore, target this age stratum

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.

Using Bayesian networks with rule extraction to infer the risk of weed infestation in a corn-crop

This paper describes the modeling of a weed infestation risk inference system that implements a collaborative inference scheme based on rules extracted from two Bayesian network classifiers. The first Bayesian classifier infers a categorical variable value for the weed-crop competitiveness using as input categorical variables for the total density of weeds and corresponding proportions of narrow and broad-leaved weeds. The inferred categorical variable values for the weed-crop competitiveness along with three other categorical variables extracted from estimated maps for the weed seed production and weed coverage are then used as input for a second Bayesian network classifier to infer categorical variables values for the risk of infestation. Weed biomass and yield loss data samples are used to learn the probability relationship among the nodes of the first and second Bayesian classifiers in a supervised fashion, respectively. For comparison purposes, two types of Bayesian network structures are considered, namely an expert-based Bayesian classifier and a naive Bayes classifier. The inference system focused on the knowledge interpretation by translating a Bayesian classifier into a set of classification rules. The results obtained for the risk inference in a corn-crop field are presented and discussed. (C) 2009 Elsevier Ltd. All rights reserved.

Identification and control of occupational risks in a Sao Paulo metropolitan region quarry

Crushed stone mining is the third largest mining economy in Brazil, where almost half is produced in the Sao Paulo metropolitan region. The segment registers the highest number of accidents among the extractive industries, which justifies the concern with workers` health and safety, and the importance of controlling occupational hazards. Since 2002, the NR-22 Standard (NR-22: Occupational Health and Safety in Mining) makes compulsory the elaboration of a Risk Management Program that identifies risks and establishes control measures. Considering the crushed stone mining industry importance to the state, this paper evaluates and discusses the risks identified in unit operations during the production process of crushed stone in an open pit mine in order to propose control measures for the development of the Risk Management Program. Although this study refers to a specific quarry, it can be applied to other mines from the same sector since some considerations are made regarding differences in manufacturing processes. The research was based on the identification of the main risks associated with drilling, blasting, load & haulage, crushing and screening through field measurements of some hazardous agents, together with company reports. The results contributed to the choice of the appropriate control measures for the improvement Of workers` health and safety conditions.

Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model

Objective: To identify prediction factors for the development of leptospirosis-associated pulmonary hemorrhage syndrome (LPHS). Methods: We conducted a prospective cohort study. The study comprised of 203 patients, aged >= 14 years, admitted with complications of the severe form of leptospirosis at the Emilio Ribas Institute of Infectology (Sao Paulo, Brazil) between 1998 and 2004. Laboratory and demographic data were obtained and the severity of illness score and involvement of the lungs and others organs were determined. Logistic regression was performed to identify independent predictors of LPHS. A prospective validation cohort of 97 subjects with severe form of leptospirosis admitted at the same hospital between 2004 and 2006 was used to independently evaluate the predictive value of the model. Results: The overall mortality rate was 7.9%. Multivariate logistic regression revealed that five factors were independently associated with the development of LPHS: serum potassium (mmol/L) (OR = 2.6; 95% CI = 1.1-5.9); serum creatinine (mmol/L) (OR = 1.2; 95% CI = 1.1-1.4); respiratory rate (breaths/min) (OR = 1.1; 95% CI = 1.1-1.2); presenting shock (OR = 69.9; 95% CI = 20.1-236.4), and Glasgow Coma Scale Score (GCS) < 15 (OR = 7.7; 95% CI = 1.3-23.0). We used these findings to calculate the risk of LPHS by the use of a spreadsheet. In the validation cohort, the equation classified correctly 92% of patients (Kappa statistic = 0.80). Conclusions: We developed and validated a multivariate model for predicting LPHS. This tool should prove useful in identifying LPHS patients, allowing earlier management and thereby reducing mortality. (C) 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

PM(2.5) and PM(10): The influence of sugarcane burning on potential cancer risk

In Brazil, sugarcane fields are often burned to facilitate manual harvesting, and this burning causes environmental pollution from the large amounts of soot released into the atmosphere. This material contains numerous organic compounds such as PAHs. In this study, the concentrations of PAHs in two particulate-matter fractions (PM(2.5) and PM(10)) in the city of Araraquara (SE Brazil, with around 200,000 inhabitants and surrounded by sugarcane plantations) were determined during the sugarcane harvest (HV) and non-harvest (NHV) seasons in 2008 and 2009. The sampling strategy included four campaigns, with 60 samples in the NHV season and 220 samples in the HV season. The PM(2.5) and PM(10) fractions were collected using a dichotomous sampler (10 L min(-1), 24 h) with Teflon (TM) filters. The filter sets were extracted (ultrasonic bath with hexane/acetone (1:1 v/v)) and analyzed by HPLC/Fluorescence. The median concentration for total PAHs (PM(2.5) in 2009) was 0.99 ng m(-3) (NHV) and 3.3 ng m(-3) (HV). In the HV season, the total concentration of carcinogenic PAHs (benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, and benzo(a)pyrene) was 5 times higher than in the NHV season. B(a)P median concentrations were 0.017 ng m(-3) and 0.12 ng m(-3) for the NHV and HV seasons, respectively. The potential cancer risk associated with exposure through inhalation of these compounds was estimated based on the benzo[a]pyrene toxic equivalence (BaP(eq)), where the overall toxicity of a PAR mixture is defined by the concentration of each compound multiplied by its relative toxic equivalence factor (TEF). BaP(eq) median (2008 and 2009 years) ranged between 0.65 and 1.0 ng m(-3) and 1.2-1.4 ng m(-3) for the NHV and HV seasons, respectively. Considering that the maximum permissible BaPeq in ambient air is 1 ng m(-3), related to the increased carcinogenic risk, our data suggest that the level of human exposure to PAHs in cities surrounded by sugarcane crops where the burning process is used is cause for concern. (C) 2010 Published by Elsevier Ltd.

Insights from Studies with Oral Cleft Genes Suggest Associations between WNT-pathway Genes and Risk of Oral Cancer

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the malignant neoplasms that arise in the mucosa of the upper aerodigestive tract. Recent studies of cleft lip/palate have shown the association of genes involved in cancer. WNT pathway genes have been associated with several types of cancer and recently with cleft lip/palate. To investigate if genes associated with cleft lip/palate were also associated with oral cancer, we genotyped 188 individuals with OSCC and 225 control individuals for markers in AXIN2, AXIN1, GSK3 beta, WNT3A, WNT5A, WNT8A, WNT11, WNT3, and WNT9B. Statistical analysis was performed with PLINK 1.06 software to test for differences in allele frequencies of each polymorphism between cases and controls. We found association of SNPs in GSK3B (p = 0.0008) and WNT11 (p = 0.03) with OSCC. We also found overtransmission of GSK3B haplotypes in OSCC cases. Expression analyses showed up-regulation of WNT3A, GSK3B, and AXIN1 and down-regulation of WNT11 in OSCC in comparison with control tissues (P < 0.001). Additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting and oral cancer.

A Comparative Study of the Frequency of Antibody and Titers Against Human Herpesvirus 8 Latent and Lytic Antigens in ""At-Risk"" Individuals and Among Patients With Kaposi`s Sarcoma

Differences in the prevalence of human herpesvirus 8 (HHV-8) and Kaposi`s sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross-sectional study aimed at detecting the frequency and titers of antibodies against HHV-8 latent and lytic antigens in serum samples from individuals with different risk-factors for HHV-8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS-KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV-8-specific antibodies to latent and lytic antigens using ""in house"" immunofluorescence assays. The results were analyzed by the Chi-square, Fisher`s exact test, Kruskal-Wallis and/or Mann-Whitney U-tests. The frequencies of HHV-8 antibodies were as follows: 87.5-100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different ""at-risk"" populations for HHV-8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high-risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS. J. Med. Virol. 81: 1292-1297, 2009. (C) 2009 Wiley-Liss, Inc.

Identification of genes associated with local aggressiveness and metastatic behavior in soft tissue tumors

Soft tissue tumors represent a group of neoplasia with different histologic and biological presentations varying from benign, locally confined to very aggressive and metastatic tumors. The molecular mechanisms responsible for such differences are still unknown. The understanding of these molecular alterations mechanism will be critical to discriminate patients who need systemic treatment from those that can be treated only locally and could also guide the development of new drugs` against this tumors. Using 102 tumor samples representing a large spectrum of these tumors, we performed expression profiling and defined differentially expression genes that are likely to be involved in tumors that are locally aggressive and in tumors with metastatic potential. We described a set of 12 genes (SNRPD3, MEGF9, SPTAN-1, AFAP1L2, ENDOD1, SERPIN5, ZWINTAS, TOP2A, UBE2C, ABCF1, MCM2, and ARL6IP5) showing opposite expression when these two conditions were compared. These genes are mainly related to cell-cell and cell-extracellular matrix interactions and cell proliferation and might represent helpful tools for a more precise classification and diagnosis as well as potential drug targets.

Quality evaluation of DNA obtained from stored human saliva and its applicability to identification in Forensic Dentistry

PURPOSE: This study evaluated the quality of DNA obtained from stored human saliva and its applicability to human identification. METHODS: The saliva samples of 20 subjects, collected in the form of saliva in natura and from mouth swabs and stored at -20ºC, were analyzed. After 7 days, the DNA was extracted from the 40 saliva samples and subjected to PCR and electrophoresis. After 180 days, the technique was repeated with the 20 swab samples. RESULTS: The first-stage results indicated that DNA was successfully extracted in 97.5% of reactions, 95% of saliva in natura and 100% of swab saliva samples, with no statistically significant difference between the forms of saliva. In the second phase, the result was positive for all 20 analyzed samples (100%). Subsequently, in order to analyze the quality of the DNA obtained from human saliva, the SIX3-2 gene was tested on the 20 mouth swab samples, and the PCR products were digested using the MbO1 restriction enzyme to evaluate polymorphisms in the ADRA-2 gene, with positive results for most samples. CONCLUSION: It was concluded that the quantity and quality of DNA from saliva and the techniques employed are adequate for forensic analysis of DNA.

Inflammation markers in healthy and periodontitis patients: a preliminary data screening

Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.

Prevalence and risk factors of apical periodontitis in endodontically treated teeth in a selected population of Brazilian adults

The aim of this study was to assess the prevalence and risk factors of apical periodontitis in endodontically treated teeth in a selected population of Brazilian adults. A total of 1,372 periapical radiographs of endodontically treated teeth were analyzed based on the quality of root filling, status of coronal restoration and presence of posts associated with apical periodontitis (AP). Data were analyzed statistically using odds ratio, confidence intervals and chi-square test. The prevalence of AP with adequate endodontic treatment was low (16.5%). This percentage dropped to 12.1% in cases with adequate root filling and adequate coronal restoration. Teeth with adequate endodontic treatment and poor coronal restoration had an AP prevalence of 27.9%. AP increased to 71.7% in teeth with poor endodontic treatment associated with poor coronal restoration. When poor endodontic treatment was combined with adequate coronal restoration, AP prevalence was 61.8%. The prevalence of AP was low when associated with high technical quality of root canal treatment. Poor coronal restoration increased the risk of AP even when endodontic treatment was adequate (OR=2.80; 95%CI=1.87-4.22). The presence of intracanal posts had no influence on AP prevalence.

Comparison between cone-beam and multislice computed tomography for identification of simulated bone lesions

There are many studies that compare the accuracy of multislice (MSCT) and cone beam (CBCT) computed tomography for evaluations in the maxillofacial region. However, further studies comparing both acquisition techniques for the evaluation of simulated mandibular bone lesions are needed. The aim of this study was to compare the accuracy of MSCT and CBCT in the diagnosis of simulated mandibular bone lesions by means of cross sectional images and axial/MPR slices. Lesions with different dimensions, shape and locularity were produced in 15 dry mandibles. The images were obtained following the cross sectional and axial/MPR (Multiplanar Reconstruction) imaging protocols and were interpreted independently. CBCT and MSCT showed similar results in depicting the percentage of cortical bone involvement, with great sensitivity and specificity (p < 0.005). There were no significant intra- or inter-examiner differences between axial/MPR images and cross sectional images with regard to sensitivity and specificity. CBCT showed results similar to those of MSCT for the identification of the number of simulated bone lesions. Cross sectional slices and axial/MPR images presented high accuracy, proving useful for bone lesion diagnosis.

Risk indicators for aggressive periodontitis in an untreated isolated young population from Brazil

This study aimed to assess the prevalence of aggressive periodontitis (AgP), and to investigate the association between demographic, socioeconomic and behavioral risk indicators with AgP in an untreated and isolated young population in Southeastern Brazil. For this cross-sectional survey, 134 subjects aged 12-29 years were selected by a census. Of those eligible, 101 subjects received a full-mouth clinical examination, and were interviewed using a structured written questionnaire. Cases were defined as individuals with 4 or more teeth with attachment loss > 4 mm or > 5 mm in the age groups 12-19 and 20-29, respectively. Overall, 9.9% of the subjects presented AgP (10.3% of the 12-19-year-olds and 9.7% of the 20-29-year-olds). The only risk indicator significantly associated with AgP in this isolated population was a high proportion of sites (> 30%) presenting supragingival calculus [OR = 23.2]. Having experienced an urgency dental treatment was a protective factor for AgP [OR = 0.1]. The authors concluded that this isolated and untreated population from Brazil presented a high prevalence of AgP. Local plaque-retaining factors played a major role in the prevalence of AgP in this isolated population, and should be included in further studies evaluating this destructive periodontal disease form.