A scanning electron microscopic study of hypercementosis

The purpose of this study was to evaluate morphological characteristics of teeth with hypercementosis that are relevant to endodontic practice. Twenty-eight extracted teeth with hypercementosis had their root apexes analyzed by scanning electron microscopy (SEM). The teeth were divided according to tooth groups and type of hypercementosis. The following aspects were examined under SEM: the contour and regularity of the root surface; presence of resorption; presence and number of apical foramina, and the diameter of the main foramen. The progression of club shape hypercementosis was directly associated with the presence of foramina and apical foramen obstruction. Cases of focal hypercementosis presented foramina on the surface, even when sidelong located in the root. Circular cementum hyperplasia form was present in 2 out of 3 residual roots, which was the highest proportion among the tooth types. The detection of a large number of foramina in the apical third of teeth with hypercementosis or even the possible existence of apical foramen obliteration contributes to understand the difficulties faced during endodontic treatment of these cases

Genetic and Environmental Contributions to Body Mass Index: Comparative Analysis of Monozygotic Twins, Dizygotic Twins and Same-Age Unrelated Siblings

Background—Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. Methods—Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age2, age3, height, height2, height3, gender and race. Results—Both non-additive genetic and common environmental contributions were significant in our model (P-values \u3c 0.0001). No significant additive genetic contribution was found. In all, 63.6% (95% confidence interval (CI) 51.8–75.3%) of the total variance of BMI was explained by a non-additive genetic component, 25.7% (95% CI 13.8–37.5%) by a common environmental component and the remaining 10.7% by an unshared component. Conclusion—Our results suggest that genetic components play an essential role in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance

Sex-specific genetic effects influence variation in body composition

Aims/hypothesis: Despite well-known sex differences in body composition it is not known whether sex-specific genetic or environmental effects contribute to these differences. Methods: We assessed body composition in 2,506 individuals, from a young Dutch genetic isolate participating in the Erasmus Rucphen Family study, by dual-energy X-ray absorptiometry and anthropometry. We used variance decomposition procedures to partition variation of body composition into genetic and environmental components common to both sexes and to men and women separately and calculated the correlation between genetic components in men and women. Results: After accounting for age

Quantitative trait locus analysis of hybrid pedigrees: variance-components model, inbreeding parameter, and power

<p>Abstract</p> <p>Background</p> <p>For the last years reliable mapping of quantitative trait loci (QTLs) has become feasible through linkage analysis based on the variance-components method. There are now many approaches to the QTL analysis of various types of crosses within one population (breed) as well as crosses between divergent populations (breeds). However, to analyse a complex pedigree with dominance and inbreeding, when the pedigree's founders have an inter-population (hybrid) origin, it is necessary to develop a high-powered method taking into account these features of the pedigree.</p> <p>Results</p> <p>We offer a universal approach to QTL analysis of complex pedigrees descended from crosses between outbred parental lines with different QTL allele frequencies. This approach improves the established variance-components method due to the consideration of the genetic effect conditioned by inter-population origin and inbreeding of individuals. To estimate model parameters, namely additive and dominant effects, and the allelic frequencies of the QTL analysed, and also to define the QTL positions on a chromosome with respect to genotyped markers, we used the maximum-likelihood method. To detect linkage between the QTL and the markers we propose statistics with a non-central χ²-distribution that provides the possibility to deduce analytical expressions for the power of the method and therefore, to estimate the pedigree's size required for 80% power. The method works for arbitrarily structured pedigrees with dominance and inbreeding.</p> <p>Conclusion</p> <p>Our method uses the phenotypic values and the marker information for each individual of the pedigree under observation as initial data and can be valuable for fine mapping purposes. The power of the method is increased if the QTL effects conditioned by inter-population origin and inbreeding are enhanced. Several improvements can be developed to take into account fixed factors affecting trait formation, such as age and sex.</p

Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study

<p>Abstract</p> <p>Background</p> <p>Adiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein. To find novel genes that influence circulating levels of adiponectin, a genome-wide linkage scan was performed on plasma adiponectin concentrations before and after 3 weeks of treatment with fenofibrate (160 mg daily) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. We studied Caucasian individuals (n = 1121) from 190 families in Utah and Minnesota. Of these, 859 individuals from 175 families had both baseline and post-fenofibrate treatment measurements for adiponectin. Plasma adiponectin concentrations were measured with an ELISA assay. All participants were typed for microsatellite markers included in the Marshfield Mammalian Genotyping Service marker set 12, which includes 407 markers spaced at approximately 10 cM regions across the genome. Variance components analysis was used to estimate heritability and to perform genome-wide scans. Adiponectin was adjusted for age, sex, and field center. Additional models also included BMI adjustment.</p> <p>Results</p> <p>Baseline and post-fenofibrate adiponectin measurements were highly correlated (r = 0.95). Suggestive (LOD > 2) peaks were found on chromosomes 1p35.2 and 3q28 (near the location of the adiponectin gene).</p> <p>Conclusion</p> <p>Two candidate genes, <it>IL22RA1 </it>and <it>IL28RA</it>, lie under the chromosome 1 peak; further analyses are needed to identify the specific genetic variants in this region that influence circulating adiponectin concentrations.</p

"Predictability of body mass index for diabetes: Affected by the presence of metabolic syndrome?"

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) and body mass index (BMI, kg.m^-2) are established independent risk factors in the development of diabetes; we prospectively examined their relative contributions and joint relationship with incident diabetes in a Middle Eastern cohort.</p> <p>Method</p> <p>participants of the ongoing Tehran lipid and glucose study are followed on a triennial basis. Among non-diabetic participants aged≥ 20 years at baseline (8,121) those with at least one follow-up examination (5,250) were included for the current study. Multivariate logistic regression models were used to estimate sex-specific adjusted odd ratios (ORs) and 95% confidence intervals (CIs) of baseline BMI-MetS categories (normal weight without MetS as reference group) for incident diabetes among 2186 men and 3064 women, aged ≥ 20 years, free of diabetes at baseline.</p> <p>Result</p> <p>During follow up (median 6.5 years); there were 369 incident diabetes (147 in men). In women without MetS, the multivariate adjusted ORs (95% CIs) for overweight (BMI 25-30 kg/m2) and obese (BMI≥30) participants were 2.3 (1.2-4.3) and 2.2 (1.0-4.7), respectively. The corresponding ORs for men without MetS were 1.6 (0.9-2.9) and 3.6 (1.5-8.4) respectively. As compared to the normal-weight/without MetS, normal-weight women and men with MetS, had a multivariate-adjusted ORs for incident diabetes of 8.8 (3.7-21.2) and 3.1 (1.3-7.0), respectively. The corresponding ORs for overweight and obese women with MetS reached to 7.7 (4.0-14.9) and 12.6 (6.9-23.2) and for men reached to 3.4(2.0-5.8) and 5.7(3.9-9.9), respectively.</p> <p>Conclusion</p> <p>This study highlights the importance of screening for MetS in normal weight individuals. Obesity increases diabetes risk in the absence of MetS, underscores the need for more stringent criteria to define healthy metabolic state among obese individuals. Weight reduction measures, thus, should be encouraged in conjunction with achieving metabolic targets not addressed by current definition of MetS, both in every day encounter and public health setting.</p

A Conserved Role for Syndecan Family Members in the Regulation of Whole-Body Energy Metabolism

Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism

A trans-ancestral meta-analysis of Genome-wide Association Studies reveals loci associated with childhood obesity

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci