A 15‐year follow‐up of first unprovoked seizures: a prospective study of 200 children

Epilepsy is associated with an extended spectrum of behaviour, psychiatric problems, and learning difficulties. The aim of this study was to establish the natural history of children with first unprovoked seizures. We studied prospectively 200 children under the age of 11 years who attended hospital emergency with a first unprovoked seizure. Demographic variables, personal and family history, neurological examination, EEG, psychiatric, and cognitive and educational profiles were analysed. Patients who developed epilepsy were characterised with respect to: time to relapse, remission rate, duration of epilepsy, neuroimaging, aetiology, epileptic syndrome, and therapeutic regimen. These results were compared to data of patients who had a single seizure over a follow‐up period of 15 years. Thirty percent of children who had a first unprovoked seizure developed epilepsy. Partial seizure type was a statistically significant variable for the development of epilepsy. An EEG with epileptic abnormalities proved to be the main risk factor for recurrence. Fifteen years later, the group with epilepsy exhibited a 2.6 greater risk of psychiatric and academic comorbidities, compared to the group without epilepsy.     

New carvacrol and thymol derivatives as potential insecticides: synthesis,biological activity,computational studies and nanoencapsulation

New compounds with potential insecticide activity were synthesized by structural modifications performed in the monoterpenoid phenolic moieties of carvacrol and thymol, resulting in a set of derivatives with the ether function containing the propyl, chloropropyl or hydroxypropyl chains, as well as a bicyclic ether with an unsaturated chain containing a carboxylic acid terminal. In addition, an analogue of carvacrol and thymol isomers bearing methoxyl, 1-hydroxyethyl and (3-chlorobenzoyl)oxy, instead of the three original methyl groups, was also synthesized. Several structural changes that resulted in diminished insecticide activity have been identified, but two significantly active molecules have been synthesized, one of them being less toxic to human cells than the naturally-derived starting materials. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these active molecules likely target the insect odorant binding proteins and/or acetylcholinesterase and are able to form stable complexes. For the most promising compounds, nanoencapsulation assays were carried out in liposomes of egg phosphatidylcholine/cholesterol (7 : 3) prepared by both thin film hydration and ethanolic injection methods. The compound-loaded liposomes were generally monodisperse and with sizes smaller than or around 200 nm. The thin film hydration method allowed high encapsulation efficiencies (above 85%) for both compounds and a delayed release, while for the systems prepared by ethanolic injection the encapsulation efficiency is lower than 50%, but the release is almost complete in two days.

Thymol and carvacrol derivatives were synthesised. Two of them proved to be mildly active against Sf9 insect cell line and one has presented selectivity by proving to be less toxic to human cells than the naturally derived starting materials.     

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (p_homogeneity = 0.42). This risk increased linearly with duration of use (p_trend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (p_homogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Studies on functional and morphological aspects in human multinodular simple goiter tissues

Samples from 2 different locations within the same euthyroid multinodular goiters (SMG) and normal (N) human thyroids were assayed for their content of DNA, thyroglobulin (Tg), and stable iodine (¹²⁷1), and determined the response of adenosine 3’,5’-cyclic monophosphate (cAMP) to TSH and NaF. Quantitative morphological estimation of histological components in the thyroid was performed and correlated with functional parameters. Regardless the zonal evaluation, in SMG the mean (± SD) DNA content (?g/mg tissue) (1.04 ± 0.86) was not statistically different from that in N (1.13 ± 0.21). The mean¹²⁷I concentration (?g/?g DNA) in N tissues (0.357 ± 0.091) was greater than that in SMG (0.176 ± 0.074). In these tissues, the Tg mean level (± SD) (?g/?g DNA) was lower (28.3 ± 21.5) than that in N (75.6 ± 41.1). The mean relative proportion (Vv) of epithelial cells in SMG (range, 6.0–30.6%) was statistically different (p <0.00) from that observed in N tissues (range, 10.4–18.2%). The meanbasal (± SD) cAMP level (pmol/?g DNA) in these tissues (0.11 1 ± 0.036) was different (p < 0.05) from that in SMG (0.231 ± 0.026). In response to TSH (10 mU), both SMG and N increased their cAMP contents to 0.454 ± 0.045 and 0.572 ± 0.020, respectively. A further elevation in cAMP levels was observed in N (1.154 ± 0.210) after 75 mU TSH, whereas in SMG tissues, no consistent increase (0.609 ± 0.496) occurred. Goiter and normal thyroid slices were unable to increase their cAMP concentrations in response to NaF in vitro. No correlation was found between functional and morphological data in SMG samples. In contrast, this relation was quite uniform in normal thyroids. The results are concordant with the intrathyroidal pathogenic processes often cited for the heterogeneity in human goiter.     

Effect of photoactivation systems and resin composites on the microleakage of esthetic restorations

AIM: The aim of this study was to evaluate the influence of four photoactivation systems [quartz tungsten halogen (QTH), light-emitting diode (LED), argon ion laser (AL), and plasma arc curing PAC)] on cementum/dentin and enamel microleakage of Class II restorations using a microhybrid [Z250-3M ESPE] and two packable composites [(SureFil-Dentsply and Tetric Ceram HB-Ivoclair/Vivadent]. METHODS AND MATERIALS: Three hundred sixty "vertical-slot Class II cavities" were prepared at the mesial surface of bovine incisors using a 245 carbide bur in a highspeed handpiece. Specimens were divided into twelve groups (composite-photoactivation systems). Half of the specimens had the gingival margin placed in enamel (n=15) and the other half in cementum/dentin (n=15). Composites were inserted and cured in 2 mm increments according to manufacturers' recommended exposure times. After polishing, the samples were immersed in 2% methylene blue solution, sectioned, and evaluated at the gingival margins. Data were submitted to statistical analysis using the Kruskal-Wallis and Mann-Whitney tests. RESULTS: No significant differences were found among the photoactivation systems and among resin composites (p>0.05). Microleakage was not significantly affected by location (enamel vs. cementum/dentin, p>0.05). These findings suggested neither the photoactivation systems nor the resin composite types might have an effect on the microleakage at gingival margins Class II cavities.     

ASSOCIATION BETWEEN POLYMORPHISM IN THE PROMOTER REGION (G/C-915) OF PAX9 GENE AND THIRD MOLAR AGENESIS

Purpose:

Hypodontia is the congenital absence of one or more (up to six) permanent and/or deciduous teeth, being one of the most common alterations of the human dentition. Genetic polymorphisms are variations of DNA sequences occurring in a population. This study investigated whether G-915C single nucleotide polymorphism (SNPs) in the PAX9 gene promoter is associated with hypodontia in humans.

Material and Methods:

The polymorphism in region G/C-915 of PAX9 gene (NCBI ref SNP ID: rs 2073247) of 240 patients was analyzed, being 110 controls and 130 individuals with third molar agenesis. After DNA extraction, the region of interest was amplified by PCR technique using two different primers. The significance of the differences in observed frequencies of polymorphisms in both groups was assessed by odds-ratio and chi-squared test with 95% confidence interval.

Results:

Genotype CC was more frequent in patients with agenesis (11.5%) compared to the control (1.8%), while GG was more prevalent in the control group (39.1%) compared to the individuals with agenesis (26.2%).

Conclusion:

These data showed that the allele C could be associated with the third molar agenesis.