GPX3 rs8177412 Polymorphism Modifies Risk of Upper Urothelial Tumors in Patients with Balkan Endemic Nephropathy.

Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16-9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27-11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75-3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development.

Association of PRDM16 rs12409277 and CtBP2 rs1561589 gene polymorphisms with lipid profile of adolescents.

Introduction: Positive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Our aim was to analyze the association of PRDM16 gene (rs12409277) and CtBP2 gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents. Material and methods: Our study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded. Results: We did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (p = 0.001) and LDL cholesterol (p = 0.008) levels compared to all other groups of genotypes. Conclusions: Our study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.

Prevalence of five pharmacologically most important CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Srpska in Bosnia and Herzegovina.

The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. Among them, CYP2C9 and CYP2C19 are clinically important, as they can mediate severe toxicity, therapy failure, and increased susceptibility to cancer and other diseases caused by chemicals. The aim of this study was to determine the prevalence of pharmacologically most important allelic variants of the CYP2C9 and CYP2C19 genes in the general population of the Republic of Srpska (Bosnia and Herzegovina) and to compare them with other populations. For this purpose we determined the genotype profile and allele frequency of 216 randomly selected healthy volunteers using real-time polymerase chain reaction (RT-PCR). The prevalence of the CYP2C9 *2 and *3 alleles was 13.6 and 7.4 %, respectively. Based on these frequencies, of the 216 participants four (1.86 %) were predicted to be poor metabolisers, 78 (36.11 %) intermediate, and the remaining 134 (62.03 %) normal metabolisers. Based on the prevalence of CYP2C19 *2 and *17 variants - 16.2 and 20.4 %, respectively - nine (4.17 %) were predicted to be poor, 57 (26.39 %) rapid, and nine (4.17 %) ultra-rapid metabolisers. We found no significant differences in allele frequencies in our population and populations from other European countries. These findings suggest that genetically determined phenotypes of CYP2C9 and CYP2C19 should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.

Perfectionism and the Five-Factor Model of Personality: A Meta-Analytic Review.

Over 25 years of research suggests an important link between perfectionism and personality traits included in the five-factor model (FFM). However, inconsistent findings, underpowered studies, and a plethora of perfectionism scales have obscured understanding of how perfectionism fits within the FFM. We addressed these limitations by conducting the first meta-analytic review of the relationships between perfectionism dimensions and FFM traits (k = 77, N = 24,789). Meta-analysis with random effects revealed perfectionistic concerns (socially prescribed perfectionism, concern over mistakes, doubts about actions, and discrepancy) were characterized by neuroticism (rc+ = .50), low agreeableness (rc+ = -.26), and low extraversion (rc+ = -.24); perfectionistic strivings (self-oriented perfectionism, personal standards, and high standards) were characterized by conscientiousness (rc+ = .44). Additionally, several perfectionism-FFM relationships were moderated by gender, age, and the perfectionism subscale used. Findings complement theory suggesting that perfectionism has neurotic and non-neurotic dimensions. Results also underscore that the (mal)adaptiveness of perfectionistic strivings hinges on instrumentation.

Autobiographical memory retrieval and appraisal in social anxiety disorder.

Individuals with social anxiety disorder (SADs; n = 41) and healthy controls (HCs; n = 40) were administered the Waterloo Images and Memories Interview, in which they described mental images that they tend to experience in both anxiety-provoking and non-anxiety-provoking social situations. Participants then recalled, in as much detail as possible, specific autobiographical memories of salient aversive and non-aversive social experiences that they believed led to the formation of these images. Audio-recorded memory narratives were transcribed and coded based on the procedure of the Autobiographical Interview, which provides a precise measure of the degree of episodic detail contained within each memory. Participants also rated the subjective properties of their recalled memories. Results revealed that participants across the two groups retrieved equivalent rates of both aversive and non-aversive social memories. However, SAD participants' memories of aversive events contained significantly more episodic detail than those of HCs, suggesting that they may be more highly accessible. Moreover, participants with SAD appraised their memories of aversive experiences as more distressing and intrusive than HCs, and perceived them as having a significantly greater influence on their self-perception. In contrast, no group differences were observed for memories of non-aversive events. Findings have the potential to shed new light on autobiographical memory in SAD, with implications for psychotherapeutic intervention.

Theory of mind ability in high socially anxious individuals.

BACKGROUND/OBJECTIVES: Research has demonstrated an association between social anxiety and impaired Theory of Mind (ToM). We assess whether ToM deficits occur even at a subclinical level of social anxiety and whether group differences in ToM performance are consistent with interpretation bias. We also explore potential reasons as to why socially anxious individuals may perform differently on ToM tasks. METHODS/DESIGN: Undergraduate participants high (HSA; n = 78) and low (LSA; n = 35) in social anxiety completed a task of ToM decoding, the Reading the Mind in the Eyes (MIE), a task of ToM reasoning, the Movie for the Assessment of Social Cognition (MASC), and a post-task questionnaire about their experience completing the MASC. RESULTS: HSAs performed marginally worse than LSAs on the MIE on neutrally valenced trials, and their pattern of errors may be consistent with a negative interpretation bias. HSAs and LSAs did not differ overall in performance on the MASC, though HSAs reported experiencing more confusion and distress than LSAs during the task, and this distress was associated with more MASC errors for HSA participants only. These results provide insight into the nature of ToM ability in socially anxious individuals and highlight important avenues for future research.

Working memory capacity in social anxiety disorder: Revisiting prior conclusions.

In one of the few studies examining working memory processes in social anxiety disorder (SAD), Amir and Bomyea (2011) recruited participants with and without SAD to complete a working memory span task with neutral and social threat words. Those with SAD showed better working memory performance for social threat words compared to neutral words, suggesting an enhancement in processing efficiency for socially threatening information in SAD. The current study sought to replicate and extend these findings. In this study, 25 participants with a principal diagnosis of SAD, 24 anxious control (AC) participants with anxiety disorders other than SAD, and 27 healthy control (HC) participants with no anxiety disorder completed a working memory task with social threat, general threat, and neutral stimuli. The groups in the current study demonstrated similar working memory performance within each of the word type conditions, thus failing to replicate the principal findings of Amir and Bomyea (2011). Post hoc analyses revealed a significant association between higher levels of anxiety symptomatology and poorer overall WM performance. These results inform our understanding of working memory in the anxiety disorders and support the importance of replication in psychological research. (PsycINFO Database Record

Are perfectionism dimensions risk factors for anxiety symptoms? A meta-analysis of 11 longitudinal studies.

BACKGROUND: Over 50 years of theory and research implicates perfectionism in anxiety. However, it is unclear which (if any) perfectionism dimensions are risk factors for anxiety. OBJECTIVE: To address this, we conducted a meta-analysis testing whether socially prescribed perfectionism, concern over mistakes, doubts about actions, self-oriented perfectionism, and personal standards predict increases in anxiety. METHOD: Our literature search yielded 11 relevant studies for inclusion, composed of children, adolescents, undergraduates, community adults, and psychiatric patients. RESULTS: Meta-analysis using random-effects models revealed concern over mistakes (r+ = .11), doubts about actions (r+ = .13), and personal standards (r+ = .08), but not socially prescribed perfectionism or self-oriented perfectionism, displayed significant small positive relationships with follow-up anxiety, after controlling for baseline anxiety. CONCLUSION: Research is needed to understand the conditions under which the connection between perfectionism and anxiety becomes stronger (e.g., stress).

The effects of social anxiety on interpersonal evaluations of warmth and dominance.

Social anxiety disorder is associated with interpersonal dysfunction, but it is not clear why people with the disorder feel unsatisfied with their relationships. One possibility is that higher social anxiety could lead to changes in sensitivity to interpersonal traits. We examined whether social anxiety moderates the types of interpersonal evaluations people make regarding warmth and dominance. We developed vignettes in which central characters systematically varied in dominance and warmth and asked two samples of participants (undergraduate students, n=176, and online workers, n=403) to rate their willingness to interact with, and the social desirability of, these characters. Participants in general reported stronger desire to interact with warmer and less dominant characters, and rated warmer and more dominant characters as being more socially desirable. People with higher social anxiety exhibited greater tolerance for colder and more submissive characters on both rated dimensions. The perceived similarity of the characters accounted for the bulk of these effects. Participants indicated a higher desire to interact with characters more similar to themselves, and people with higher social anxiety were more likely to rate submissive and cold characters as being like themselves. The results have implications for clinical interventions for social anxiety disorder.