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OBJECTIVE: Nonsyndromic cleft lip with or without cleft palate (NSCL±P) is a common craniofacial anomaly with multifactorial etiology. Evidence suggests that variations in WNT pathway genes contribute to an increased susceptibility to NSCL±P. The aim of this study was to investigate the association of AXIN1, APC, CTNNB1, DVL2, and GSK3ß gene variants with NSCL±P in a case-control data set from Brazil. PATIENTS: 471 individuals with NSCL±P and 504 unrelated control individuals of Caucasian ethnicity. DESIGN: Twenty single-nucleotide polymorphisms (SNPs) in/nearby AXIN1, APC, CTNNB1, DVL2, and GSK3B genes were genotyped using Taqman chemistry in a Viia7 sequence detection instrument. Genotype, allele, and haplotype frequencies were compared among NSCL±P patients and controls using Fisher exact test, implemented in PLINK software. The level of significance was established at P ≤.002 under Bonferroni correction. In silico analysis of SNP function was assessed using MirSNP database. RESULTS: Significant association was found between GSK3B rs13314595 genotypes and NSCL±P ( P = .0006). Additionally, nominal associations were found between DVL2 (rs35594616) and APC (rs448475) with NSCL±P ( P = .02 and P = .03, respectively). SNP haplotypes for GSK3B and APC genes showed nominal associations with NSCL±P ( P < .05). In silico analysis predicted that APC rs448475 harbors a binding site for the microRNA miR-617 and that the switch from a G allele to C allele enhances binding, whereas DVL2 rs35594616 did not appear to harbor microRNA-binding sites. CONCLUSION: This study shows for the first time the association between GSK3B and NSCL±P and confirms the role of additional WNT pathway genes as candidates for NSCL±P.

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In the present study, persistent organic pollutants (POPs) were determined in 14 livers from specimens of the Brazilian sharpnose shark (Rhizoprionodon lalandii), which is an important economic resource for small-scale fisheries on the southeastern coast of Brazil. The following concentrations (lipid weight) of POPs were found: ∑PCBs: 1019±267 ng g(-1); ∑DDTs: 111±40 ng g(-1) and ∑PBDEs: 10.4±4.78. PCB 153 made the greatest contribution to ∑PCB (21.4%), followed by PCB 138 (14.6%) and PCB 180 (9.94%). Among chlorinated pesticides, only the p,p'-DDE and p,p'-DDD isomers had concentrations above the detection limit. Moreover, levels above the detection limit were found only for PBDE congeners 47 and 100 (BDEs 47>99). On average, BDE 47 accounted for 88% of the total PBDE load. The feeding habits of the Brazilian sharpnose shark close to the Brazilian coastline are likely the most important difference regarding the accumulation of POPs in comparison to oceanic species that feed in deeper waters. Thus, this species may be used to evaluate the pollution of coastal areas as well as human exposure to contaminants, as the Brazilian sharpnose shark is a frequently used for human consumption. Further studies in other areas of Brazil and involving other species are needed to clarify the mechanisms and potential impact of POPs, which can affect the biology of different organisms and cause population declines.

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OBJECTIVE: This study aimed to evaluate the effect of adenotonsillectomy on visual attention and daytime sleepiness in children with sleep-disordered breathing. DESIGN: This was a controlled prospective cohort study. SETTING: Outpatients from the Otorhinolaryngology Division of Edmundo Vasconcelos Hospital Complex, São Paulo, Brazil. PARTICIPANTS: Patients aged 6-17 years with upper airway obstruction scheduled to undergo adenotonsillectomy (treatment group) in the Otorhinolaryngology Division of Edmundo Vasconcelos Hospital Complex, in São Paulo, Brazil. Participants of control group were consecutively selected from another outpatient clinic of paediatric surgery, but those with symptoms of sleep-disordered breathing were excluded. MAIN OUTCOME MEASURES: Children were submitted to visual attention tests (TAVIS-3) that discriminates normal subjects from those with attentional disorders in advance of the surgery and 2 months later, and in the same period for the control group. Parents were interviewed about lifestyle, sleep characteristics and daytime sleepiness. RESULTS: The analysis included 27 patients in the adenotonsillectomy group and 30 controls, who had similar age (10.0 ± 3.3 versus 10.3 ± 3.7 years; P = 0.8), gender (41% boys versus 57%, respectively) and body mass index. There was marked decrease in daytime sleepiness after surgery (delta between groups: -4.7 ± 3.8; P < 0.001), as well as reductions in reaction time, errors of omission and errors of commission in the treatment compared with the control group at both time points, before and after surgery. CONCLUSIONS: This study shows that adenotonsillectomy in children and adolescents with sleep-disordered breathing reduces daytime sleepiness and improves the performance in tests of visual attention.

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Hexachlorocyclohexane (HCH) isomers (α-, ß- and γ- HCH [lindane]) were recently added to the list of persistent organic pollutants regulated by the Stockholm Convention, and therefore, the legacy of HCH and lindane production has become an issue of global relevance. The production of lindane with the much larger quantities of associated waste isomers has generated large waste deposits and contaminated sites. This article presents an overview of HCH-polluted sites in Brazil as a basis for further activities related to the Stockholm Convention. The locations of HCH stockpiles and contaminated sites in Brazil arising from production and formulation have been compiled and mapped. This shows that the measures taken over the past 25 years have not resulted in remediation of the HCH pollution. An exposure risk study has been summarised for one major site and is included to demonstrate the contemporary relevance of the contamination. Major site remediation efforts are planned at one site but people live close to several other sites, and there is an urgent need of further assessments and remediation to ensure the protection of human health and the environment. The Stockholm Convention requires a systematic approach and should be adopted for the assessment of all sites and appropriate isolation/remediation measures should be facilitated. The appropriate planning of these activities for the production site in Rio de Janeiro could be a positive contribution for Rio+20 highlighting that green economy and sustainable production also include the appropriate management of legacies of historic production of an industrial sector (here the organochlorine industry).

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OBJECTIVES: The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection. METHODS: Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment. RESULTS: A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality. CONCLUSION: The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients.

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OBJECTIVE: To assess changes in the prevalence of otitis media, associated with the use of highly active antiretroviral therapy, in Brazilian human immunodeficiency virus (HIV) infected children. SETTING: Division of otorhinolaryngology, Hospital das Clínicas, Sao Paulo University Medical School, Brazil. PATIENTS: A cohort of 459 HIV-infected children aged below 13 years. MAIN OUTCOME MEASURES: The prevalence of otitis media and the serum cluster of differentiation four glycoprotein T lymphocyte count were compared for children receiving highly active antiretroviral therapy (with protease inhibitors) and those receiving standard antiretroviral therapy (without protease inhibitors). RESULTS: Otitis media was present in 33.1 per cent of the children. Children aged from zero years to five years 11 months receiving highly active antiretroviral therapy had a higher prevalence of acute otitis media (p=0.02) and a lower prevalence of chronic otitis media (p=0.02). Children who were receiving highly active antiretroviral therapy had a mean serum cluster of differentiation four glycoprotein T lymphocyte count greater than that of those who were receiving standard antiretroviral therapy (p<0.001). CONCLUSIONS: The use of highly active antiretroviral therapy in Brazilian HIV-infected children was associated with a lower prevalence of chronic otitis media.

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INTRODUCTION: Oral candidosis (OC) and hairy leukoplakia (OHL) are important markers of Human Immunodeficiency Virus (HIV) infection immune status. OBJECTIVES: to evaluate if OC and/or OHL should be considered clinical predictors of immune and virologic failure on HIV-infected Brazilian adults undergoing Highly Active Antiretroviral Therapy (HAART). METHODS: 124 HIV-infected patients who used HAART for a minimum of six months were prospectively evaluated. All of them under-took oral examination and serum CD4+ count and viral load (VL), being divided in two groups, P and A, respectively according to the presence or absence of OC and/or OHL. During a six month period, patients belonging to group A were followed. They were re-examined for new oral lesions. New blood samples were collected and they were subdivided into groups P6 and A6. CD4+ count and VL were compared between groups at baseline and after the six months period. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and relative risk (RR) were obtained in order to assess the accuracy of using OC and OHL as predictors of immune and virologic failure, at baseline and after a six month period. RESULTS: At baseline and after six months, patients with OC and OHL have mean CD4+ count lower and mean VL higher than patients of group A and A6 (p < 0.001). OC had high PPV for immune failure and a moderated PPV for virologic failure. OHL had low PPVs for both measures. DISCUSSION AND CONCLUSIONS: OC and OHL still indicate low serum CD4+ count and high VL, but OC seems to be a better predictor of immune and virologic failure in patients undergoing HAART than OHL.

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Polychlorinated biphenyls (PCBs) are ubiquitous anthropogenic compounds found even in the polar regions, mainly due to long-range atmospheric transport. In order to assess the occurrence of atmospheric PCBs in the vicinity of the Brazilian Antarctic Research Station (62 degrees 05'S, 58 degrees 23'W), a sampling survey was undertaken in the austral summer of 1995-1996. The concentrations of the PCB congeners in the air ranged from not detected to 33.2 pgm(-3). The lower chlorinated congeners (PCB-101 and below), which are more volatile and subject to long-range transport, predominated in the air samples and represented 66.7% of the total PCB concentrations. Atmospheric levels of PCBs were correlated with meteorological conditions and the highest levels were associated with the passage of the frontal systems coming from South America.