Using the Bayesian variational spike and slab model in a genome-wide association study for finding associated loci with bipolar disorder.

OBJECTIVE: The genome-wide association studies (GWAS) analysis, the most successful technique for discovering disease-related genetic variation, has some statistical concerns, including multiple testing, the correlation among variants (single-nucleotide polymorphisms) based on linkage disequilibrium and omitting the important variants when fitting the model with just one variant. To eliminate these problems in a small sample-size study, we used a sparse Bayesian learning model for finding bipolar disorder (BD) genetic variants. METHODS: This study used the Wellcome Trust Case Control Consortium data set, including 1998 BD cases and 1500 control samples, and after quality control, 380,628 variants were analysed. In this GWAS, a Bayesian logistic model with hierarchical shrinkage spike and slab priors was used, with all variants considered simultaneously in one model. In order to decrease the computational burden, an alternative inferential method, Bayesian variational inference, has been used. RESULTS: Thirteen variants were selected as associated with BD. The three of them (rs7572953, rs1378850 and rs4148944) were reported in previous GWAS. Eight of which were related to hemogram parameters, such as lymphocyte percentage, plateletcrit and haemoglobin concentration. Among selected related genes, GABPA, ELF3 and JAM2 were enriched in the platelet-derived growth factor pathway. These three genes, along with APP, ARL8A, CDH23 and GPR37L1, could be differential diagnostic variants for BD. CONCLUSIONS: By reducing the statistical restrictions of GWAS analysis, the application of the Bayesian variational spike and slab models can offer insight into the genetic link with BD even with a small sample size. To uncover related variations with other traits, this model needs to be further examined.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

A wide range of missing imputation approaches in longitudinal data: a simulation study and real data analysis.

BACKGROUND: Missing data is a pervasive problem in longitudinal data analysis. Several single-imputation (SI) and multiple-imputation (MI) approaches have been proposed to address this issue. In this study, for the first time, the function of the longitudinal regression tree algorithm as a non-parametric method after imputing missing data using SI and MI was investigated using simulated and real data. METHOD: Using different simulation scenarios derived from a real data set, we compared the performance of cross, trajectory mean, interpolation, copy-mean, and MI methods (27 approaches) to impute missing longitudinal data using parametric and non-parametric longitudinal models and the performance of the methods was assessed in real data. The real data included 3,645 participants older than 18 years within six waves obtained from the longitudinal Tehran cardiometabolic genetic study (TCGS). The data modeling was conducted using systolic and diastolic blood pressure (SBP/DBP) as the outcome variables and included predictor variables such as age, gender, and BMI. The efficiency of imputation approaches was compared using mean squared error (MSE), root-mean-squared error (RMSE), median absolute deviation (MAD), deviance, and Akaike information criteria (AIC). RESULTS: The longitudinal regression tree algorithm outperformed based on the criteria such as MSE, RMSE, and MAD than the linear mixed-effects model (LMM) for analyzing the TCGS and simulated data using the missing at random (MAR) mechanism. Overall, based on fitting the non-parametric model, the performance of the 27 imputation approaches was nearly similar. However, the SI traj-mean method improved performance compared with other imputation approaches. CONCLUSION: Both SI and MI approaches performed better using the longitudinal regression tree algorithm compared with the parametric longitudinal models. Based on the results from both the real and simulated data, we recommend that researchers use the traj-mean method for imputing missing values of longitudinal data. Choosing the imputation method with the best performance is widely dependent on the models of interest and the data structure.

Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

Effect of C-reactive protein on the risk of Heart failure: a mendelian randomization study.

BACKGROUND: Traditional observational studies have shown positive associations between c-reactive protein (CRP) and heart failure (HF) risk. However, this association has not been fully elucidated. Therefore, Mendelian randomization was used to examine CRP's possible etiological roles with HF. METHODS: We implemented a two-sample Mendelian randomization framework to examine the causality of the association between CRP and HF based on summary statistics by large-scale genome-wide association studies (GWAS) datasets of European ancestry through inverse-variance weighted, weighted median, MREgger regression, and MR-PRESSO methods. The summary statistics dataset on the association of genetic variants with CRP was used from the published GWAS of European descent in UK Biobank participants (N = 427,367) and the CHARGE consortium (N = 575,531). The GWAS dataset used to identify genetic variants underlying HF from the HERMES consortium includes 977,323 participants (47,309 cases and 930,014 controls). The odds ratio (OR) with 95% confidence intervals (CIs) was employed to examine this association. RESULTS: The results of our IVW indicated that CRP was strongly associated with HF (OR = 4.18, 95% CI = 3.40-5.13, p < 0.001). The Cochran heterogeneity test showed significant heterogeneity among SNPs of CRP (Q = 317.55, p < 0.001; I2 = 37.6%), and no considerable pleiotropy was detected for the association of CRP with HF [intercept = 0.003; p = 0.234]. This finding remained consistent using different Mendelian randomization methods and sensitivity analyses. CONCLUSION: Our MR study did identify convincing evidence to support CRP associated with HF risk. Human genetic data suggest that CRP is a causative factor in HF. Hence, CRP assessment may offer additional prognostic information as an adjuvant to overall risk assessment in HF patients. These findings prompt significant questions about the function of inflammation in the progression of HF. More research into the role of inflammation in HF is needed to guide trials of anti-inflammation management.

Familial resemblance and family-based heritability of nutrients intake in Iranian population: Tehran cardiometabolic genetic study.

BACKGROUND: We aimed to investigate the familial resemblance of dietary intakes, including energy and nutrients, and the family-based heritability of dietary intake in different age-sex dyads of the Tehran cardiometabolic genetic study. METHODS: This cross-sectional study was conducted on 9,798 participants, aged ≥ 18 years, with complete data in each of the third, fourth, fifth, and sixth surveys of the Tehran Cardiometabolic Genetic study, who were eligible to enter the current study based on inclusion and exclusion criteria. Nutrient intake was determined using a valid and reliable food frequency questionnaire (FFQ). FCOR command of the S.A.G.E. software was used to estimate the intra-class correlation coefficients of all relative pairs to verify the family resemblance of dietary nutrient intakes. Classical likelihood-based is used to assess the family-based heritability of dietary nutrient traits. RESULTS: There were 4338 families with a mean family size of 3.20 ± 2.89, including 1 to 32 members (2567 constituent pedigrees and 1572 singletons) and 3627 sibships. The mean ± SD age of participants was 42.0 ± 15.2 years, and 44.5% were males. The heritability of nutrient intake ranged from 3 to 21%. The resemblance degree of energy intake and most nutrients between spouses or between parents and children is weak to moderate; however, a high resemblance of intake was observed for some food components, especially among spouses, including trans fatty acids (TFAs) (r:0.70), chromium (r:0.44), fiber(r:0.35), pantothenic acid (r:0.31), and vitamin C(r:0.31). Based on our findings, the resemblance of nutrient intake in spouses was greater than in parent-offspring. The similarity in parent-offspring nutrient intake was different, and the correlation in mother-girls nutrient intakes was greater than other parent-child correlations. Also, the lowest resemblance in nutrient intake was observed among siblings. CONCLUSIONS: Our findings suggested a weak-to-moderate similarity between the nutrient intakes of parents and offspring. The resemblance degree in nutrient intake varied between different family pairs; the strongest correlation of nutrients was observed between spouses, which includes TFAs, chromium, fiber, pantothenic acid, and vitamin C. The lowest correlation of nutrients was between siblings, such as carbohydrates, thiamine, niacin, and vitamin K. An individual's nutrient intake can somewhat be influenced by genetics, family relationships, and the effects of parents, although the significant influence of environmental factors should not be ignored.

Evaluating machine learning-powered classification algorithms which utilize variants in the GCKR gene to predict metabolic syndrome: Tehran Cardio-metabolic Genetics Study.

BACKGROUND: Metabolic syndrome (MetS) is a prevalent multifactorial disorder that can increase the risk of developing diabetes, cardiovascular diseases, and cancer. We aimed to compare different machine learning classification methods in predicting metabolic syndrome status as well as identifying influential genetic or environmental risk factors. METHODS: This candidate gene study was conducted on 4756 eligible participants from the Tehran Cardio-metabolic Genetic study (TCGS). We compared predictive models using logistic regression (LR), Random Forest (RF), decision tree (DT), support vector machines (SVM), and discriminant analyses. Demographic and clinical features, as well as variables regarding common GCKR gene polymorphisms, were included in the models. We used a 10-repeated tenfold cross-validation to evaluate model performance. RESULTS: 50.6% of participants had MetS. MetS was significantly associated with age, gender, schooling years, BMI, physical activity, rs780094, and rs780093 (P < 0.05) as indicated by LR. RF showed the best performance overall (AUC-ROC = 0.804, AUC-PR = 0.776, and Accuracy = 0.743) and indicated BMI, physical activity, and age to be the most influential model features. According to the DT, a person with BMI < 24 and physical activity < 8.8 possesses a 4% chance for MetS. In contrast, a person with BMI ≥ 25, physical activity < 2.7, and age ≥ 33, has 77% probability of suffering from MetS. CONCLUSION: Our findings indicated that, on average, machine learning models outperformed conventional statistical approaches for patient classification. These well-performing models may be used to develop future support systems that use a variety of data sources to identify persons at high risk of getting MetS.

Serum adiponectin and cortisol levels are not affected by studied ADIPOQ gene variants: Tehran lipid and glucose study.

BACKGROUND: Obesity is a major public health concern in developed and even developing countries worldwide. Adiponectin is a protein secreted by adipose tissue that modulates many metabolic processes and plays a vital role in obesity. This study aimed to determine the association of four variants of the ADIPOQ gene with serum adiponectin, cortisol levels and obesity status. METHODS: This case-control study was performed on 164 obese individuals compared by 156 control from the Tehran Lipid and Glucose Study (TLGS). Standard procedures obtained anthropometric measures and metabolic parameters. Cortisol and adiponectin levels were measured by ELISA method. rs1501299, rs266729, rs17300539, and rs17366743 on the ADIPOQ gene were genotyped using the PCR-RFLP. The correlation between adiponectin gene SNPs and obesity were calculated by Additive, dominant, and recessive genetic models. Pearson's or Spearman's found correlations between adiponectin levels and metabolic and anthropometric variables. Data were analyzed using SPSS software Version 20. RESULTS: Adiponectin and cortisol levels were significantly lower in obese subjects compared to the control group (p < 0.05). There was a significant negative correlation between serum adiponectin level and BMI, waist circumference (WC), waist-hip ratio, hip circumference (HC), Fasting blood sugar (FBS) Triglyceride (TG), Total cholesterol (TC), Systolic blood pressure (SBP), Diastolic blood pressure (DBP) (r = - 0.147, r = - 0.324, r = 0.371, r = - 0.179, r = - 0.299, r = - 0.277, r = - 0.041, r = - 0.134, and r = - 0.149, respectively). A positive correlation was found between adiponectin and high-density lipoprotein cholesterol (HDL-C) (r = 0.29), but no significant correlations were found between adiponectin and Low-density lipoprotein cholesterol(LDL-C) and cortisol. ADIPOQ variant rs1501299 was significantly associated with cortisol levels in subjects with BMI ≥ 25 (P-value =0.039). CONCLUSIONS: Adiponectin and cortisol levels were associated with obesity. No ADIPOQ gene variants and haplotypes were associated with cortisol, Adiponectin, and obesity.

The resemblance of dietary intakes in three generations of parent-offspring pairs: Tehran lipid and glucose study.

The degree of similarity between dietary intakes of offspring and their parents may be different across various countries. This study aimed to investigate the correlation between food group intakes and dietary quality in three younger-middle-older generations by living arrangements. Individuals who participated in the 5th survey of the Tehran Lipid and Glucose Study, 1286 families (4685 subjects) with complete data for two or three generations were entered in this cross-sectional study. Genetic data management system from Progeny Software was used to error-check family data pedigree details. Dietary data were gathered using a valid and reliable food frequency questionnaire. The healthy eating index score was computed. Data of parents with their offspring were compared using paired t-test and partial correlation. The mean ages of grandfathers and grandmothers were 69.4 ± 7.9 and 63.7 ± 8.5 respectively. Of girls and boys who lived with their parents, about 59% were 20 years or older. The correlation of parents' dietary intake and their young offspring who lived with them was higher than that of parents and adult offspring who lived independently from their parents. The correlation of dietary quality and food group intakes in mother-offspring dyads (mother-son: 0.37, mother-daughter: 0.44) were higher than father-offspring (father-son: 0.34, father-daughter: 0.25) dyads. The dietary quality of parents was higher than that of offspring in both living statuses. The dietary intake of adult married offspring was not correlated with their parents; also there was no correlation between the dietary quality of younger and older generations. There were weak to moderate similarities between food group intakes of parent-offspring dyads that lived with their parents.

Familial genetic and environmental risk profile and high blood pressure event: a prospective cohort of cardio-metabolic and genetic study.

BACKGROUND AND AIMS: High blood pressure is the heritable risk factor for cardiovascular diseases. We investigated whether the presence of familial genetic and environmental risk factors are associated with increased risk of high blood pressure. METHODS: A total of 4,559 individuals from 401 families were included in this study. Familial aggregation analysis was carried out on systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC), and heritability was estimated for SBP and DBP. The association between familial risk factors and blood pressure traits including, incidence of hypertension, SBP and DBP was estimated separately using regression-based two-level Haseman-Elston (HE) method, with individual and familial BMI and WC as environmental exposures and familial genetic profile of known variants as genetic risk factors in 210 index families (≥2 hypertensive cases). Models were adjusted for the two nested sets of covariates. RESULTS: During a follow-up of 15 years, the SBP, DBP, BMI and WC were highly correlated in inter class of mother-offspring and intraclass of sister-sister with heritability of 30 and 25% for DBP and SBP, respectively. Among index families, those whose members with higher familial BMI or WC had significantly increased risk of hypertension and consistent, strong signals of rs2493134 (AGT) linked with SBP and DBP, rs976683 (NLGN1) linked with SBP and HTN, and epistasis of rs2021783 (TNXB) and known genetic variants linked with all blood pressure traits. CONCLUSIONS: Findings from this study show that familial genetic and environmental risk profile increase risk for high blood pressure beyond the effect of the individuals' own risk factors.

The joint effect of PPARG upstream genetic variation in association with long-term persistent obesity: Tehran cardio-metabolic genetic study (TCGS).

PURPOSE: This study is the first study that aims to assess the association between SNPs located at the PPARG gene with long term persistent obesity. In this cohort association study, all adult individuals who had at least three consecutive phases of BMI (at least nine years) in Tehran genetic Cardio-metabolic Study (TCGS) were included. METHODS: Individuals who always had 30 ≤ BMI < 35 and individuals who always had 20 < BMI ≤ 25 were assigned to the long-term persistent obese group and persistent normal weight group, respectively. Other individuals were excluded from the study. We used four gamete rules to make SNP sets from correlated nearby SNPs and kernel machine regression to analyze the association between SNP sets and persistent obesity or normal weight. RESULTS: The normal group consisted of 1547 individuals with the mean age of 40 years, and the obese group consisted of 1676 individuals with mean age of 48 years. Two groups had a significant difference between all measured clinical characteristics at entry time. The kernel machine result shows that nine correlated SNPs located upstream of PPARG have a significant joint effect on persistence obesity. CONCLUSION: This is the first study on the association between PPARG variants with persistent obesity. Three of the nine associated markers were reported in previous GWAS studies to be associated with related diseases. For the studied markers in the PPARG gene, the Iranian allele frequency was near the American and European populations. LEVEL III: Case-control analytic study.

Lack of association between FTO gene variations and metabolic healthy obese (MHO) phenotype: Tehran Cardio-metabolic Genetic Study (TCGS).

BACKGROUND: Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes. MATERIALS AND METHODS: We selected 954 adult subjects from TCGS (47.9% male). Participants were stratified according to their BMI and presence of metabolic syndrome according to the Joint Interim Statement (JIS) definition. Nine selected polymorphisms from FTO/CETP genes were genotyped using Tetra ARMS-PCR method. After age and sex adjustment the interaction of 9 markers with lipid profiles among phenotypes were tested by PASW. RESULTS: In three main groups, HDL_C level had a strong significant association with CETP markers: (rs3764261, ß(95% CI) - 0.48(- 0.61 to - 0.35), P = 1.0 × 10-11), (rs1800775, ß(95% CI) 0.5(0.36;0.65), P = 1.0 × 10-6) and (rs1864163, ß(95% CI) 0.3(0.16;0.43), P = 9.1 × 10-5). This association was also seen in rs7202116 within the total population. In only unhealthy metabolic obese (MUHO) subgroups four new FTO markers (rs1421085, rs1121980, rs1558902 and rs8050136) (P value < 0.01) demonstrated significant association, even after lipid profile adjustment. CONCLUSION: In the present study, we investigated the association between obesity phenotypes and some variations in FTO/CETP genes for the first time. Our study showed that four markers in the first intron of the FTO gene should be the risk marker in MUHO participants. LEVEL OF EVIDENCE: Level III, case-control study.

Generality of genomic findings on blood pressure traits and its usefulness in precision medicine in diverse populations: A systematic review.

Remarkable findings from genome-wide association studies (GWAS) on blood pressure (BP) traits have made new insights for developing precision medicine toward more effective screening measures. However, generality of GWAS findings in diverse populations is hampered by some technical limitations. There is no comprehensive study to evaluate source(s) of the non-generality of GWAS results on BP traits, so to fill the gap, this systematic review study was carried out. Using MeSH terms, 1545 records were detected through searching in five databases and 49 relevant full-text articles were included in our review. Overall, 749 unique variants were reported, of those, majority of variants have been detected in Europeans and were associated to systolic and diastolic BP traits. Frequency of genetic variants with same position was low in European and non-European populations (n = 38). However, more than 200 (>25%) single nucleotide polymorphisms were found on same loci or linkage disequilibrium blocks (r2 ≥ 80%). Investigating for locus position and linkage disequilibrium of infrequent unique variants showed modest to high reproducibility of findings in Europeans that in some extent was generalizable in other populations. Beyond theoretical limitations, our study addressed other possible sources of non-generality of GWAS findings for BP traits in the same and different origins.

The role of matrix metalloproteinase-9 as a prognostic biomarker in papillary thyroid cancer.

BACKGROUND: The aim of the present study was to investigate the association between matrix metalloproteinase-9 (MMP-9) expression with BRAF V600E mutation and clinicopathological features, in Iranian papillary thyroid cancer (PTC) patients. METHODS: In total, 90 participants including 60 PTC patients (15 males and 45 females) and 30 individuals with benign multinodular goiter (MNG) (5 males and 25 females) which were confirmed by surgical pathology, were investigated. MMP-9 was evaluated at both mRNA and protein levels, using SYBR-Green Real-Time PCR and enzyme-linked immune sorbent assay (ELISA), respectively. BRAF V600E mutation was detected by sequencing. RESULTS: Mean age of PTC and MNG patients was 37.6 ± 12.6 and 48.1 ± 13.3 years, respectively (P = 0.001). BRAF V600E mutation was found in 24 of the 60 (40%) PTC cases, with mean tumor size of 1.59 ± 1.20 cm. MMP-9 mRNA levels were elevated in tumoral compared to the adjacent non-tumoral tissues (P = 0.039); moreover, this rise was also observed in PTC patients compared to MNG patients (P = 0.001). The mRNA levels of MMP-9 increased in patients aged≥45 years (P = 0.015), those with lymphovascular invasion (P = 0.003), and higher tumor stages (III and IV) (P = 0.011). The protein level of MMP-9 increased in tumoral compared to adjacent non-tumoral tissues (P < 0.001); this increase was also found in PTC patients compared to MNG participants (P = 0.004). MMP-9 protein level was higher in patients aged≥45 years (P = 0.001), those with lymphovascular invasion (P = 0.036) and higher TNM stages (III and IV) (P = 0.001). Area under the ROC curve (AUC) was 0.70 (95%CI: 0.57-0.83, P = 0.003), with 91.4% sensitivity and 51.9% specificity at the cutoff value of 0.50. CONCLUSION: The mRNA and protein levels of MMP-9 had no association with BRAF V600E mutation in Iranian PTC patients. These levels were associated with age, TNM stages, and lymphovascular invasion, being defined as malignant factors. Thus, elevated levels of MMP-9 in PTC patients compared to MNG participants illustrated that it can be used as a potential biomarker to differentiate PTC patients from those with MNG.

Comparison of Cuspal Deflection and Microleakage of Premolar Teeth restored with Three Restorative Materials.

AIM: This study aimed to assess cuspal deflection and micro-leakage of mesio-occluso-distal (MOD) cavities in premolar teeth restored with three different tooth-colored restorative materials to determine the effect of polymerization shrinkage stress over time. MATERIALS AND METHODS: The MOD cavities (4 mm depth) were prepared in 30 sound human maxillary premolars. The teeth were randomly divided into three groups (n = 10). The teeth were then restored with Filtek P60 (group I), X-tra fil (group II), and Admira Fusion x-tra (group III). Cuspal deflection was assessed after 5 minutes, 24 hours, 48 hours, and 7 days by measuring the intercuspal distance. After restoring the teeth, they were subjected to 1,000 thermal cycles and were then immersed in 2% methylene blue for 24 hours. After vertical section of teeth, they were observed under a stereomicroscope to assess micro-leakage. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's honest significant difference (HSD) post hoc test. Friedman test was used to compare different time points in each group and nonparametric Mann-Whitney test was applied to assess microleakage (a < 0.05). RESULTS: The mean cuspal deflection was significantly different in the three groups (p < 0.001). The highest deflection was noted in Filtek P60 (14.8 ± 1.9) and the lowest was noted in Admira Fusion x-tra (7.4 ± 1.4 µm). Cuspal deflection significantly decreased after 7 days, but did not return to the baseline value. Admira Fusion x-tra showed significantly less deflection after 7 days (p < 0.001), but the other two groups were the same (p = 0.3). Microleakage was not significantly different among the three groups (p > 0.05). CONCLUSION: The lowest cuspal deflection was noted in Admira Fusion x-tra, although marginal microleakage was not significantly different among the groups. CLINICAL SIGNIFICANCE: As the lowest cusp deflection was noted in Admira Fusion x-tra, this restorative material can be suitable for esthetic restoration of extensive posterior cavities.

Effect of Er: YAG Laser, Sandblast and Several Types of Universal Bonding on Shear Bond Strength of Zirconia Ceramic to Composite Resin.

AIM: The purpose of this study was to investigate the effect of Erbium-doped yttrium aluminium garnet laser laser (Er: YAG laser), sandblast and several universal bonding on the shear bond strength of zirconia ceramic to composite resin. MATERIALS AND METHODS: In this experimental study, 96 Y-TZP disks were used. They were divided into six groups based on surface preparation: 1-Er: YAG laser + single bond universal/ 3M, 2-Er: YAG laser + all bond universal/bisco, 3-Er: YAG laser + G-premio bond/GC, 4-sandblast + single bond universal/3M, 5-sandblast + all bond universal/bisco, 6-sandblast + G-Premio bond/GC; in the next step, composite discs were cured on the surface of the zirconia discs and their shear bond strength was evaluated using a mechanical test machine (universal testing machine). RESULTS: Two-way ANOVA showed that the surface preparation had a significant statistical effect on shear bond strength (p< 0.001). There was no association between these two variables with regards to the interaction of bonding and surface preparation (p = 0.064). Tukey's test showed that the shear bond strengths in the sandblast type group did not differ significantly between the groups according to the type of universal bonding, as well as in the Er: YAG laser treated group by type Universal bonding which was not significantly different between the groups of single bond universal and all bond universal, but there was a significant difference between the groups in terms of single bond universal and G-Premio, as well as all bond universal and G-Premio. CONCLUSION: Based on the results, the preparation of Er:YAG laser is a more appropriate method for increasing bond strength when compared with sandblasting, and among the universal bonding, G-Premio is also more suitable for this purpose. CLINICAL SIGNIFICANCE: The present data indicate that bond strength of laser preparation and G-Premio adhesive might be reliable for clinical application Keywords: Er: YAG Laser, Sandblasting, Shear bond strength, Universal bonding.

The role of burnout syndrome as a mediator for the effect of psychosocial risk factors on the intensity of musculoskeletal disorders: a structural equation modeling approach.

This study examined the hypothesis that burnout syndrome mediates effects of psychosocial risk factors and intensity of musculoskeletal disorders (MSDs) among hospital nurses. The sample was composed of 415 nurses from various wards across five hospitals of Iran's Hamedan University of Medical Sciences. Data were collected through three questionnaires: job content questionnaire, Maslach burnout inventory and visual analogue scale. Results of structural equation modeling with a mediating effect showed that psychosocial risk factors were significantly related to changes in burnout, which in turn affects intensity of MSDs.

Energy and macronutrient intake heritability: A systematic review and meta-analysis of twin and family-based studies.

BACKGROUND/AIMS: The current meta-analysis aimed to examine the heritability and familial resemblance of dietary intakes, including energy and macronutrients in both twin and family-based studies. METHODS: The online literature databases, including PubMed, Scopus, and Web of Science were searched comprehensively until 2023 to identify the relevant studies. The heritability index in family studies was h2 and the heritability indices for twin studies were h2, A2, and E2. Three weighted methods were used to calculate the mean and SE of heritability dietary intakes. RESULTS: Eighteen papers including 8 studies on familial population and 12 for twin population studies were included in the present meta-analysis. The heritability of dietary intakes in twin studies (range of pooled estimated h2, A2, and E2 was 30-55%, 14-42%, and 52-79%, respectively) was higher than family studies (range of pooled estimated h2 = 16-39%). In family studies, the highest and lowest heritability for various nutrients was observed for the fat (%Kcal) (h2 range:36-38%) and carbohydrate in g (h2 range:16-18%), respectively. In twin studies, based on mean h2, the highest and lowest heritability for various nutrients was reported for the fat (%Kcal) (h2 range:49-55%) and protein intake in g (h2 range:30-35%), respectively. Also, based on the mean of A2, the highest and lowest heritability was observed for carbohydrates (% Kcal) (A2 range:42-42%), and protein (% Kcal) (A2 range:14-16%), respectively. Furthermore, in twin studies, the highest and lowest mean of E2 was shown for saturated fats (E2 range:74-79%) and energy intake (E2 range:52-57%), respectively. CONCLUSION: Our analysis indicated that both environmental factors and genetics have noticeable contributions in determining the heritability of dietary intakes. Also, we observed higher heritability in twins compared to family studies.

Three candidate SNPs show associations with thyroid-stimulating hormone in euthyroid subjects: Tehran thyroid study.

Objectives: Previous studies have shown interindividual variation in free thyroxine (FT4) serum levels and thyroid stimulating hormone (TSH) in healthy persons. Genetic factors mainly determine this variation, and genome-wide association studies have increased the number of thyroid function-associated variants. The present study investigates the association of candidate variants with FT4 and TSH in a euthyroid Iranian population. Method: A total of 2931 unrelated euthyroid subjects (FT4 10.29-21.88 pmol/L; TSH 0.32-10 mIU/L, thyroid peroxidase antibody TPOAb < 33 IU/mL in men and < 35 IU/mL in women), with available genotypes were chosen from the Tehran Thyroid Study (TTS), to examine the impact of selected SNPs on thyroid hormone under the additive genetic model. In order to evaluate regional associations with FT4 and TSH levels, a haplotype analysis was done. Results: We identified a strong association between the rs4338740-C allele and TSH in the adjusted model (ß = -0.095, P-value = 0.0004). Also, findings indicated that rs4954192 ACMSD and rs4445669 CADM1 correlated with normal TSH levels (P-value = 0.011, P-value = 0.014, respectively). Haplotype analysis revealed that two haplotypes were significantly associated with TSH levels in euthyroid individuals. The ACGA and AC haplotypes on chromosomes 8 and 14 were significantly correlated with normal TSH levels, respectively (P-value = 0.014, P-value = 0.016). Conclusions: This is the first genetic association study with TSH and FT4 reference values in an Iranian population. Our findings indicate that a few gene variants associated with the reference values of TSH in other populations are also associated with the reference values of TSH in Iranians. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01383-2.

Parent-child correlation in energy and macronutrient intakes: A meta-analysis and systematic review.

In the current study, we aimed to review the evidence from twin and family-based studies that have assessed the familial similarity in intakes of energy and macronutrients among various parent-child pairs. The online literature databases, including Web of Science, PubMed, and Scopus, were searched up to December 2022 to find potentially eligible studies. We converted Pearson's, Spearman's, or intra-class correlation coefficients to z's using Fisher's z transformation to obtain approximate normality and then calculated a mean and standard error (SE) of transformed correlation weighted by the sample sizes in the studies. We reported pooled r and 95% CI as our final results in five groups, including parent-child, mother-daughter, mother-son, father-daughter, and father-son. Twenty-one eligible studies were included in this meta-analysis, in which the sample size ranged from 33 and 4310. Our analysis showed that family resemblance in the intake of energy and macronutrients in various parent-offspring pairs was weak to moderate which could be different based on family pairs, nutrients, and studies. The highest similarity in dietary intakes was observed among the mother-daughter pair, which was for carbohydrate and protein intake, respectively. The lowest correlations in dietary intakes were found between mother-son or father-son pairs. Our meta-analysis suggested that family similarity for intakes of energy and macronutrients was not strong in parent-child pairs. The highest correlation in dietary intake was mostly found in mother-daughter pairs. The weak similarities in dietary intake among parent-child pairs indicate the noticeable effect of the environment outside the family on individuals' dietary choices.