High dosage folic acid supplementation, oral cleft recurrence and fetal growth

Objectives: To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth. Patients and Methods: The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates. Results: The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group. Conclusions: The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Profiles of gene polymorphisms in cytokines and toll-like receptors with higher risk for gastric cancer

Background: Chronic inflammation and gastric carcinogenesis show a close association, so gene polymorphisms that modify the intensity of the inflammatory response may contribute to variations in gastric cancer risk. Aims: The purpose of this study was to investigate the combined effect of the pro- and anti-inflammatory cytokines and toll-like receptors polymorphisms on the chronic gastritis and gastric cancer risk in a Brazilian population sample. Methods: We evaluated 669 DNA samples (200 of gastric cancer [GC], 229 of chronic gastritis [CG], and 240 of healthy individuals [C]). Ten polymorphisms were genotyped: IL-1RN and TLR2 -196 to -174 del using the allele-specific PCR method and TNF-A (rs1800629; rs1799724), TNF-B (rs909253), IL-8 (rs4073; rs2227532), IL-10 (rs1800872) and TLR4 (rs4986790; rs4986791) using PCR-RFLP. Results: Polymorphisms TNF-A-308G/A, IL-8-251A/T, TNF-B + 252A/G and TLR4 + 1196C/T were not associated with risk of any gastric lesion. However, an association with increased risk for GC was observed for polymorphisms IL-1RNL/2 (p < 0.001), TNF-A-857C/T (p = 0.022), IL-8-845T/C (p < 0.001), IL-10-592C/A (p < 0.001), TLR2ins/del (p < 0.001), and TLR4 + 896A/G (p = 0.033). In CG, an association was observed only with polymorphisms IL-1RNL/2 and IL-10-592A/C (p < 0.001 for both). A combined analysis of these six polymorphisms associated with GC revealed a profile with two to four combined genotypes which confer a higher risk of gastric carcinogenesis, with an OR increased 2.95-fold to 50.4-fold, highlighting the combinations IL-1RN2/TNF-A-857T/IL-8-845C, IL-1RN2/IL-8-845C/TLR2del, IL-1RN2/IL-10-592A/TLR4 + 896G, IL-10-592A/TLR2del/ TLR4 + 896G, and IL-1RN2/TNFA-857T/IL8-845C/TLR2del. Conclusions: Our findings evidenced that the combined effect of polymorphisms in genes involved in the inflammatory process may potentiate the risk of gastric cancer, thus emphasizing the importance of evaluating multiple polymorphisms together. © 2012 Springer Science+Business Media New York.

Influence of risk behavior aggregation in different categories of physical activity on the occurrence of cardiovascular risk factors

Background: We aimed to verify the association of risk behavior aggregation in different categories of physical activity (PA) with the presence of cardiovascular risk factors (RF) employees at a public university. Method. We analyzed data of 376 employees, which were visited in their workplace for measurement of weight, height and questionnaires to identify the risk behaviors and risk factors. Chi-square test was used to analyze the association between the dependent and independent variables and binary logistic regression was used to construct a multivariate model for the observed associations. Results: Associations were found between the aggregation of following risk behaviors: smoking, alcohol consumption and physical inactivity, considered in different categories of PA, and the increase in RF, except for the presence of hypertriglyceridemia. Individuals with two or more risk behaviors in occupational PA category are more likely to be hypertensive (3.04 times) and diabetes (3.44 times). For the free time PA category, these individuals were 3.18 times more likely to have hypercholesterolemia and for locomotion PA, more likely to be hypertensive (2.42 times) and obese (2.51 times). Conclusion: There are association between the aggregation of two or more risk behaviors and the presence of cardiovascular RF. © 2013 Bernardo et al.; licensee BioMed Central Ltd.

Acute toxicity and environmental risk of teflubenzuron to Daphnia magna, Poecilia reticulata and Lemna minor in the absence and presence of sediment

This study aimed to estimate the acute toxicity of teflubenzuron (1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea) (TFB) for Daphnia magna, Lemna minor and Poecilia reticulata, in the absence and presence of sediment; evaluate the effect of sediment on the TFB bioavailability; and to classify this insecticide according to its environmental poisoning risk for agricultural and aquaculture uses. The tests of TFB acute toxicity were conducted in static system in a completely randomized design with increasing TFB concentrations, and a control group. The TFB has been classified according to the estimated values of EC50 and LC50 by its acute toxicity and environmental risk. The sediment significantly reduced toxicity and bioavailability of TFB in water column. Therefore, the insecticide can be classified as being highly toxic to Daphnia magna, which means the agricultural and aquacultural uses of TFB pose a high risk of environmental toxicity to non-target organisms. However, it was practically non-toxic to L. minor and P. reticulata. © 2013 Copyright Taylor and Francis Group, LLC.

Different tools for estimating cardiovascular risk in Brazilian postmenopausal women

Objective: To compare estimation of cardiovascular risk using the Framinghan Risk Score (FRS) and the presence of the metabolic syndrome (MetS) in postmenopausal women to prevent primary cardiovascular disease (CVD). Methods: This cross-sectional study included 497 Brazilian women (aged 45 years and amenorrhea >12months). Cardiovascular risk was calculated using the FRS that includes age, total cholesterol, HDL, systolic blood pressure and smoking status. Women showing three or more of the following criteria were diagnosed with MetS: waist circumference (WC) >88cm, blood pressure 130/85mmHg, triglycerides 150mg/dl, HDL<50mg/dl and glucose 100mg/dl. For statistical analysis, the Chi-square, Fisher's exact, and logistic regression (odds ratio-OR) were used. Results: The mean age was 55.3±7.0 years and time since menopause 7.2±5.9 years. Based on FRS, 72.4% of women were classified as low-risk, 16.5% moderate risk and 11.1% a high-risk. MetS was identified in 40% of the women, and 46.2% were considered of moderate risk for CVD, while 84.9% of those without MetS were classified as low-risk (p<0.001). The risk for CVD increased significantly with age at menopause (OR1.10; 95% CI, 1.04-1.17), time since menopause (OR1.13; 95% CI, 1.08-1.18), elevated triglycerides (OR1.03; 95% CI, 1.0-1.10) and presence of MetS (OR1.72; 95% CI 1.48-1.84). Conclusions: By using only FRS to estimate cardiovascular risk, a substantial number of postmenopausal women showing evidence of MetS were not identified, even though women with MetS are at higher risk of CVD. © 2013 Informa UK Ltd.

Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Le(a-b-) phenotype: potential risk factor for infection by the RH strain of Toxoplasma gondii in pregnancy

The Lewis histo-blood group system is characterized by the expression of the Lea and Le(b) antigens in the gastrointestinal tract, whose synthesis results in interactions between alpha 2-L-fucosyltransferase (FUTII) and alpha 3/4-L-fucosyltransferase (FUTIII) enzymes coded by the FUT2 (19q. 13.3) and FUT3 (19p13.3) genes. FUTII and FUTIII fucosylate the type 1 oligosaccharide precursor (Gal beta 1 -> 3NAcGlc beta 1 -> 3-R) at distinct positions to form H type 1 (Fuc alpha 1. 2Gal beta 1. 3NAcGlc beta 1 -> 3-R) and Le(a) (Gal beta 1 -> 3[Fuc alpha 1 -> 4] NAcGlc beta 1 -> 3-R) antigens, respectively. The fucosylation of H type 1 antigens by FUTIII results in the Leb antigen (Fuc alpha 1. 2Gal beta 1. 3[Fuca1. 4] NAcGlc beta 1. 3-R). Thus, the presence of the FUTII and FUTIII enzymes leads to the expression of the Le(a+b+) phenotype, while the presence of only FUTIII allows the expression of the Le(a+b-) phenotype. The absence of the FUTIII enzyme leads to the expression of the Le(a-b-) phenotype, independent of the presence or absence of FUTII. Point mutations in FUT2 and FUT3 genes change the activity of these enzymes, impair the synthesis of Le(a) and Le(b) antigens, and contribute to the variability of Lewis phenotypes in the gastrointestinal tract. Toxoplasma gondii, an apicomplexan parasite that infects a large proportion of the world's population, utilizes the gastrointestinal tract as an infection route and seems to adhere to glycosylated molecules to invade human cells. These apparently independent events may be related. The aim of this study was to test the hypothesis that there is an association between the Lewis histo-blood group system and infection by T. gondii. Two hundred and nine serum samples collected from pregnant women were submitted to screening tests to detect anti-T. gondii antibodies, employing the indirect hemagglutination method. ELISA was utilized to identify IgG class anti-T. gondii antibodies specific for the RH strain. A hundred and ninety-five samples with concordant results for both methods were selected to form two groups: seropositive (G1) and seronegative (G2). The G428A mutation of the FUT2 gene, and T202C and C314T of the FUT3 gene, which allow inference of the gastrointestinal tract Lewis phenotypes, were identified using PCR-RFLP and PCR-SSP methods, respectively. Among the 195 samples selected, 116 (59.5%) were seropositive and 79 (40.5%) were seronegative. In G1, 68 (58.6%) were classified as Le(a+b+), 30 (25.9%) as Le(a+b-), and 18 (15.5%) as Le(a-b-), and in G2, 67 (84.8%) were classified as Le(a+b+), 12 (15.2%) as Le(a+b-), and 0 (0%) as Le(a-b-) (P < 0.0001). The Le(a-b-) phenotype is associated with a high risk of RH strain T. gondii infection when compared with the Le(a+b+) [P = 0.0001; OR = 36,460; 95%CI = 2.152-617,680] and Le(a+b-) phenotypes [P = 0.0118; OR = 15,165; 95%CI = 0.8463-271,710]. The Le(a+b-) phenotype showed a higher risk compared to the Le(a+b+) phenotype [P = 0.0206; OR = 2463; 95%CI = 2463-5214]. The results suggest that the Le(a-b-) phenotype is strongly associated with a greater risk of infection by the RH strain of T. gondii compared to the other phenotypes. It is possible that the absence of fucosylation of the type 1 oligosaccharide precursor as well as the variations in the structures of the Le(a) and Le(b) antigens influence susceptibility to infection by this parasite.

Musculoskeletal disorders in upper limbs in dental students: exposure level to risk factors

Aim: This study assessed the risk factors of undergraduate students to develop musculoskeletal disorders (MSD) in the upper limbs, regarding gender, type of dental clinical procedure, mouth region treated, and the four-handed dentistry practice. Methods: Dental students enrolled in the 8th semester in the Araraquara School of Dentistry, UNESP, Brazil, were photographed while practicing 283 dental procedures. The Rapid Upper Limb Assessment (RULA) method was used to evaluate the working postures of each student. The photographs were evaluated and a final risk score was attributed to each analyzed procedure. The prevalence of risk factors of developing MSD was estimated by point and by 95% confidence interval. The association between the risk factor of developing disorders and variables of interest were assessed by the chi-square test with a significance level of 5%. Results: The risk factors of developing MSD were high, regarding most dental procedures performed by the undergraduate students (score 5: 7.07%, CI95%: 4.08- 10.06%; score 6: 62.54%, CI95%: 56.90-68.18%). There was no significant association between the RULA final score and gender (p=0.559), and type of dental procedure (p=0.205), and mouth regions by arch (p=0.110) or hemi-arch (p=0.560), and the use of four-handed dentistry (p=0.366). Conclusions: It can be concluded that gender, type of dental clinical procedure, mouth region treated, and practice of four-handed dentistry did not influence the risk of developing MSD in the upper limbs among the dental students evaluated; however, they are at a high risk of developing such disorders.

Use of the probability of stone formation (PSF) score to assess stone forming risk and treatment response in a cohort of Brazilian stone formers

Introduction: The aim was to confirm that PSF (probability of stone formation) changed appropriately following medical therapy on recurrent stone formers.Materials and Methods: Data were collected on 26 Brazilian stone-formers. A baseline 24-hour urine collection was performed prior to treatment. Details of the medical treatment initiated for stone-disease were recorded. A PSF calculation was performed on the 24 hour urine sample using the 7 urinary parameters required: voided volume, oxalate, calcium, urate, pH, citrate and magnesium. A repeat 24-hour urine sample was performed for PSF calculation after treatment. Comparison was made between the PSF scores before and during treatment.Results: At baseline, 20 of the 26 patients (77%) had a high PSF score (> 0.5). Of the 26 patients, 17 (65%) showed an overall reduction in their PSF profiles with a medical treatment regimen. Eleven patients (42%) changed from a high risk (PSF > 0.5) to a low risk (PSF < 0.5) and 6 patients reduced their risk score but did not change risk category. Six (23%) patients remained in a high risk category (> 0.5) during both assessments.Conclusions: The PSF score reduced following medical treatment in the majority of patients in this cohort.

Hormonal contraceptive use before hCG remission does not increase the risk of gestational trophoblastic neoplasia following complete hydatidiform mole: a historical database review

To re-evaluate the safety of hormonal contraceptives (HC) after uterine evacuation of complete hydatidiform mole (CHM). Historical database review. Charing Cross Hospital Gestational Trophoblastic Disease Centre, London, United Kingdom. Two thousand four hundred and twenty-three women with CHM of whom 154 commenced HC while their human chorionic gonadotropin (hCG) was still elevated, followed between 2003 and 2012. We compared time to hCG remission between HC users and nonusers. The relationship between HC use and gestational trophoblastic neoplasia (GTN) development was assessed. The relationship between HC use and a high International Federation of Gynecology and Obstetrics (FIGO) risk score was determined. Time to hCG remission, risk of developing postmolar GTN and proportion of women with high FIGO risk score. No relationship was observed between HC use with mean time to hCG remission (HC users versus non-users: 12 weeks in both, P = 0.19), GTN development (HC users versus non-users: 20.1 and 16.7%, P = 0.26) or high-risk FIGO score (HC users versus nonusers: 0% and 8%, P = 0.15). Moreover, no association between HC and GTN development was found, even when an age-adjusted model was used (OR = 1.37, 95% CI 0.91-2.08, P = 0.13). The use of current HC is not associated with development of postmolar GTN or delayed time to hCG remission. Therefore, HC can be safely used to prevent a new conception following CHM regardless of hCG level. Non-concurrent cohort study to re-evaluate the safety of low dose HCs after uterine evacuation of CHM.

Muskuloskeletal disorders in upper limbs in dental students: exposure level to risk factors

Aim: This study assessed the risk factors of undergraduate students to develop musculoskeletaldisorders (MSD) in the upper limbs, regarding gender, type of dental clinical procedure, mouthregion treated, and the four-handed dentistry practice. Methods: Dental students enrolled in the8th semester in the Araraquara School of Dentistry, UNESP, Brazil, were photographed whilepracticing 283 dental procedures. The Rapid Upper Limb Assessment (RULA) method was usedto evaluate the working postures of each student. The photographs were evaluated and a finalrisk score was attributed to each analyzed procedure. The prevalence of risk factors of developingMSD was estimated by point and by 95% confidence interval. The association between the riskfactor of developing disorders and variables of interest were assessed by the chi-square test witha significance level of 5%. Results: The risk factors of developing MSD were high, regardingmost dental procedures performed by the undergraduate students (score 5: 7.07%, CI95%: 4.08-10.06%; score 6: 62.54%, CI95%: 56.90-68.18%). There was no significant association betweenthe RULA final score and gender (p=0.559), and type of dental procedure (p=0.205), and mouthregions by arch (p=0.110) or hemi-arch (p=0.560), and the use of four-handed dentistry (p=0.366).Conclusions: It can be concluded that gender, type of dental clinical procedure, mouth regiontreated, and practice of four-handed dentistry did not influence the risk of developing MSD in theupper limbs among the dental students evaluated; however, they are at a high risk of developingsuch disorders.(AU).