Pitfalls of X-chromosome inactivation testing in females with Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding alpha-galactosidase A (AGAL). The impact of X-chromosome inactivation (XCI) on the phenotype of female FD patients remains unclear. In this study we aimed to determine pitfalls of XCI testing in a cohort of 35 female FD patients. XCI was assessed by two methylation-based and two allele-specific expression assays. The results correlated, although some variance among the four assays was observed. GLA transcript analyses identified crossing-over in three patients and detected mRNA instability in three out of four analyzed null alleles. AGAL activity correlated with XCI pattern and was not influenced by the mutation type or by reduced mRNA stability. Therefore, AGAL activity may help to detect crossing-over in patients with unstable GLA alleles. Tissue-specific XCI patterns in six patients, and age-related changes in two patients were observed. To avoid misinterpretation of XCI results in female FD patients we show that (i) a combination of several XCI assays generates more reliable results and minimizes possible biases; (ii) correlating XCI to GLA expression and AGAL activity facilitates identification of cross-over events; (iii) age- and tissue-related XCI specificities of XCI patterning should be considered.

Guilt, shame and their associations with chronic diseases in Czech adults.

The interest in the association between feelings of guilt and shame and psychological health is growing. However, less attention so far has been paid to the associations with chronic disease. Therefore, the aim of this study was to explore whether feelings of guilt and shame are related to physical health in chronic disease and in selected ones. A nationally representative sample of Czech adults (n = 1000, age = 46.0 ± 17.3 years, 48.6% men) participated in the survey. Feelings of guilt and shame (items from The Positive and Negative Affect Schedule) and health problems in selected chronic diseases were measured. Respondents with higher feelings of guilt - but not of shame - were more likely to suffer from a chronic disease; we found this in arthritis, back pain, cardiovascular disease, asthma, cancer and depression or anxiety. The association was strongest in the case of cancer with odds ratios (OR) 5.83 (95% confidence interval (CI) 2.27-16.69). There were no significant associations in case of diabetes and stroke. Feelings of shame were not related to chronic diseases. Our findings suggest that feelings of guilt are associated with worse physical health. Further research is needed in this area.

Cyberbullying: The Discriminant Factors Among Cyberbullies, Cybervictims, and Cyberbully-Victims in a Czech Adolescent Sample.

Although the research on cyberbullying has increased dramatically in recent years, still little is known about how cyberbullying participant groups (i.e., cyberbullies, cybervictims, and cyberbully-victims) differ from one another. This study aims to discriminate between these groups at an individual and relational level by controlling for age and gender. Self-control, offline aggression, and self-esteem are analyzed as individual-level variables. Parental attachment and peer rejection are involved as relational-level variables. A total of 2,092 Czech adolescents aged 12 to 18 were enrolled from a random sample of 34 primary and secondary schools located in the South Moravian region of the Czech Republic. Discriminant function analyses indicated that the participant groups are discriminated by two functions. The first function increases the separation between cyberbullies and cyberbully-victims from cybervictims, indicating that cyberbullies and cyberbully-victims are similar to each other in terms of low self-control, offline aggression, and gender, and have higher scores on measures of low self-esteem and offline aggression. However, cyberbully-victims had the highest scores on these measures. The second function discriminates between all three groups, which indicates that those variables included in the second function (i.e., parental attachment, peer rejection, self-esteem, and age) distinguish all three involved groups.